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Evidence-based Treatment Options for Autism

Published on Jul 01, 2017

Autism Integrated Care Program

If there is one clear take-away from 2 decades worth of autism research, it is this: Early diagnosis of autism spectrum disorder (ASD) coupled with prompt, evidence-based and effective intervention will result in the best possible prognosis for the child.

All children with ASD — or even a suspected diagnosis — can benefit from early intervention (EI). Research shows that in an appropriate educational setting, EI for at least 2 years prior to the start of school can result in significant improvements, and some may gain enough skills to successfully enter a regular education elementary school setting. Effective programs focus on developing communication, social and cognitive skills. Physicians should suggest patients begin EI services as soon as the diagnosis is made. If patients have a long wait between a positive screen and a diagnostic evaluation, it’s best to initiate EI even before a formal diagnosis is made.

The most effective treatments available today are applied behavioral analysis, occupational therapy, speech therapy, physical therapy, and pharmacological therapy. Treatment works to minimize the impact of the core features and associated deficits of ASD and to maximize functional independence and quality of life. In 2012, the Missouri Autism Guidelines Initiative summarized the findings from 6 reviews on behavioral and pharmacological interventions in autism. The consensus paper includes current evidence of what interventions have been studied and shown effective.

Applied behavior analysis (ABA)

ABA uses behavioral psychology principles to systematically change behavior by encouraging positive behaviors and discouraging negative ones. In addition, ABA teaches new skills and applies those skills to new situations.

Pivotal response training (PRT) 

RPT is a form of incidental or naturalistic ABA aimed at increasing a child’s motivation to learn, monitor their own behavior, and initiate communication with others by focusing on behaviors that are seen as key to learning other skills, such as language, play and social skills. PRT works to generalize skills across many settings with different people.

Discrete trial teaching 

Is a common form of ABA in which what is being taught is broken down into smaller steps, then using prompts and rewards for each step. Prompts and rewards are phased out over time.

Early Start Denver Model (ESDM)

ESDM is a comprehensive ABA program for infants, toddlers and preschoolers ages 12 to 48 months with ASD. ESDM includes naturalistic ABA, interpersonal exchange, shared enjoyment in joint activities, and promotion of language and communication. The emphasis is on having fun within a developmental framework. Parent involvement is key to the success of the intervention. ESDM has been shown to be effective in a randomized clinical trial. Children who received 20 hours of ESDM per week (5 of the hours provided by parents) over 2 years showed more improvement in cognitive testing (IQ), adaptive skills, and autism symptoms than those who received typical community treatment.

Lovaas Model

The Lovaas Model consists of 20 to 40 hours of highly structured, discrete trial teachings, integrating ABA techniques into an early intervention (EI) program for children between the ages of 2 and 8 years, and no later than age 12. The technique utilizes child-specific reinforcers to motivate and reward success. Additionally, the use of language and imitation are crucial in this teaching model.

Speech therapy

Since people with ASD have deficits in social communication, speech therapy is an important component of treatment. A licensed speech-language pathologist (SLP) helps to improve a child’s communication skills, allowing them to better express their needs or wants. Speech therapy is often most effective when SLPs work with teachers, support personnel, families, and the child’s peers to promote functional communication in natural settings.

If a child is nonverbal and unable to develop verbal communication skill, the use of gestures, sign language, and picture communication programs are often useful tools to improve their abilities to communicate.

Occupational therapy (OT)

OT is often used as a treatment for the sensory integration issues associated with ASD. It is also used to help teach life skills that involve fine-motor movements, such as dressing, using utensils, cutting with scissors and writing. OT works to improve quality of life and the ability to participate fully in daily activities. Each OT program is based on individual evaluations and goals. OT for young children with ASD often focuses on improving sensory integration and sensorimotor issues. In older children, OT often focuses on improving social behavior and increasing independence.

Physical therapy (PT)

PT is used to improve gross motor skills and handle sensory integration issues, particularly those involving the individual’s ability to feel and be aware of their body in space. Similar to OT, physical therapy is used to improve the child’s ability to participate in everyday activities. PT works to teach and improve skills such as walking, sitting, coordination, and balance. PT is most effective when integrated in an EI program.

Medications

Pharmaceutical treatments can ameliorate some of the behavioral symptoms of ASD, including irritability, aggression and self-injurious behavior. By medically reducing interfering or disruptive behaviors, other treatments, including ABA, may be more effective. Medications should be prescribed and monitored by a qualified physician.

• Risperidone  is the first Food and Drug Administration-approved medication for the treatment of symptoms associated with of ASD in children and adolescents, including aggressive behavior, deliberate self-injury, and temper tantrums.
• Aripriprazole  is also FDA-approved for the treatment of irritability in children and adolescents with ASD. A 2009 study published in Pediatrics found that in a group of 98 children, by week 8, 52% of those taking aripiprazole (in the form of Abilify®) experienced a 25% or greater reduction in autism-related irritability symptoms compared with 14% of those who took the placebo.

Reference and suggested readings

The Missouri Autism Guidelines Initiative. Autism Spectrum Disorders: Guide to Evidence-based Interventions: a 2012 Consensus Publication . The Missouri Autism Guidelines Initiative. www.autismguidelines.dmh.mo.gov . Accessed June 5, 2917.

Zwaigenbaum L, Bauman ML, Choueiri R, et al. Early intervention for children with autism spectrum disorder under 3 years of age: recommendations for practice and research.  Pediatrics.  2015;136 Suppl 1:S60-S81.

Makrygianni MK, Reed P. A meta-analytic review of the effectiveness of behavioural early intervention programs for children with autistic spectrum disorders.  Research in Autism Spectrum Disorders.  2010; 4 (4);577-593.

The Lovaas Model. The Lovaas Institute website. http://www.lovaas.com . Accessed June 5, 2017.

Dawson G, Rogers S, Munson J, et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics . 2010:125(1):e17-e23. [Early Start Denver Model]

Arnold LE, Vitiello B, McDougle C, et al. Parent-defined target symptoms respond to risperidone in RUPP autism study: customer approach to clinical trials.  J Am Acad Child Adolesc Psychiatry.  2003;42(12):1443-1450.

McCracken JT, McGough J, Shah B, et al . Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347(5):314-321

Myers SM, Johnson CP. Management of children with autism spectrum disorders.  Pediatrics. 2007;120(5):1162-1182.

Scahill L, McDougle CJ, Aman MG, et al .  Effects of risperidone and parent training on adaptive functioning in children with pervasive developmental disorders and serious behavioral problems.  J Am Acad Child Adolesc Psychiatry. 2012;51(2):136-146.

Shea S, Turgay A, Carroll A, et al. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders.  Pediatrics. 2004;114(5):e634-e641.

Troost PW, Lahuis BE, Steenhuis MP, et al. Long-term effects of risperidone in children with autism spectrum disorders: a placebo discontinuation study.  J Am Acad Child Adolesc Psychiatry.  2005:44(11);1137-1144.

Aman MG, Kasper W, Manos G, et al. Line-item analysis of the Aberrant Behavior Checklist: results from two studies of aripiprazole in the treatment of irritability associated with autistic disorder.  J Child Adolesc Psychopharmacol. 2010;20(5):415-422.

Marcus RN, Owen R, Kamen L, et al. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder.  J Am Acad Child Adolesc Psychiatry. 2009;48(11):1110-9.

Marcus RN, Owen R, Manos G, et al. Safety and tolerability of aripiprazole for irritability in pediatric patients with autistic disorder: a 52-week, open-label, multicenter study. J Clin Psychiatry. 2011;72(9):1270-6.

Owen, R, Sikich L, Marcus RN,  et al.  Aripiprazole in the Treatment of Irritability in Children and Adolescents With Autistic Disorder.  Pediatrics. 2009;124(6):1533-40.

Stigler, KA, Diener JT, Kohn AE, et al. Aripiprazole in pervasive developmental disorder not otherwise specified and Asperger’s disorder: a 14-week, prospective, open-label study.  J Child Adolesc Psychopharmacol.  2009;19(3):265-274.

Contributed by: Amanda E. Bennett, MD, MPH

Categories: Children’s Doctor Summer 2017 , Autism Spectrum Disorder

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• Open access
• Published: 02 March 2023

Comprehensive ABA-based interventions in the treatment of children with autism spectrum disorder – a meta-analysis

• Theresa Eckes 1 ,
• Ulrike Buhlmann 1 ,
• Heinz-Dieter Holling 1 &
• Anne Möllmann 1 , 2  

BMC Psychiatry volume  23 , Article number:  133 ( 2023 ) Cite this article

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Many studies display promising results for interventions that are based on Applied Behavior Analysis (ABA) in the treatment of autism spectrum disorder (ASD). Methods: This meta-analysis assessed the effects of such treatments on developmental outcomes in children with ASD and on parental stress based on 11 studies with 632 participants. Results: Compared to treatment as usual, minimal or no treatment, comprehensive ABA-based interventions showed medium effects for intellectual functioning (standardized mean difference SMD = 0.51, 95% CI [0.09; 0.92]) and adaptive behavior (SMD = 0.37, 95% CI [0.03; 0.70]). Language abilities, symptom severity or parental stress did not improve beyond the improvement in control groups. Moderator analyses indicate that language abilities at intake could influence the effect sizes and the influence of treatment intensity might decrease with older age. Conclusions: Practical implications and limitations are discussed.

Peer Review reports

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by (a) difficulties in social communication and interaction across multiple contexts and (b) restricted, repetitive behavior, activities, and interests. It is often associated with intellectual impairment, language impairment, and motor deficits, such as odd gait or clumsiness [ 1 ]. According to the clinical criteria of ASD laid out in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5; [ 1 ]), the prevalence of ASD is approximately 1.0% and people on the autistic spectrum need intensive, sometimes life-long care and support [ 2 ].

Behavioral interventions for ASD target the increase of functional independence of individuals on the autistic spectrum. They are firmly linked to Applied Behavior Analysis (ABA) [ 2 , 3 ]. ABA is the science of analyzing how the individual’s environment influences their behavior [ 4 ] and describes interventions applying the findings of such analyses to change behavior [ 5 , 6 ]. It is theoretically based on operant conditioning and aims to assess and change challenging behavior as well as to promote and generalize more adaptive behavior, for example, by using systematic reinforcement [ 5 ]. While ABA-based methods can be used to target specific behaviors (e.g,. toilet training), comprehensive ABA-based interventions are characterized by (a) beginning in early childhood, when possible between 3 to 4 years of age; (b) having a high intensity (20 – 40 h/week); (c) being personalized to meet the individual needs of each child; (d) addressing several skills at the same time instead of promoting just one specific skill (e.g., joint attention); and (e) using multiple behavior analytic methods. Additionally, comprehensive ABA-based interventions (f) use a one-to-one format that is gradually supplemented with group activities and transferred to naturalistic contexts, and (g) require parental participation ([ 7 ] as cited in [ 8 ]). Well-known examples for comprehensive ABA-based interventions are Early Intensive Behavioral Interventions (EIBI) [ 4 ], which make up the majority of the studies considered in the present study. However, since some comprehensive, intensive ABA-based methods are not called EIBI, for instance the Verbal Behavior approach (ABA-VB, for a detailed description see [ 9 ]), we will use the term comprehensive ABA-based interventions rather than EIBI in our study. While treatment goals in behavioral interventions are most often in line with typical sequences of development (e.g., the promotion of more adaptive behavior), another group of interventions is explicitly designed on applying behavioral methods (e.g., methods based on ABA) and developmentally-based strategies in naturalistic settings, deriving individual learning objectives from developmental sequences [ 10 ]. Those interventions are called Naturalistic Developmental Behavioral Interventions (NDBI) [ 10 ]. A prominent example for NDBI is the Early Start Denver Model (ESDM). This group of treatment interventions shows good evidence of efficacy in recent meta-analyses [ 11 , 12 ]. Because of conceptual differences, NBDIs are not included in the present meta-analysis.

Comprehensive ABA-based interventions are widely used in North America in the treatment of ASD. In Europe, however, comprehensive ABA-based programs are rarely applied [ 13 ], among other things due to the claim that they are not evidence-based [ 2 ]. This claim is rooted in the fact that many studies that investigate comprehensive ABA-based therapies are of poor methodological quality [ 2 , 14 ]. As Reichow and colleagues [ 14 ] showed in their meta-analysis, many studies investigating the effects of EIBI in autistic children have small samples, a non-optimal design and a high risk of bias according to the GRADE system. Additionally, other reasons like financial or cultural obstacles when implementing comprehensive ABA-based treatments are discussed [ 13 ]. It should not be neglected that some aspects (e.g., the intensive use of reinforcement) of comprehensive ABA-based treatments raised ethical concerns about this approach [ 13 , 15 ]. However, comprehensive ABA-based interventions, like EIBI, provide a substantiated theoretical basis.

Nine meta-analyses on the effects of comprehensive ABA-based interventions on intellectual functioning, adaptive behavior (e.g., communication skills and socialization) and language abilities were published between 2009 and 2018 [ 8 , 16 – 23 ]. Eight meta-analyses found comprehensive ABA-based interventions to be more effective in the treatment of children with ASD than standard care [ 8 , 16 , 1 , 18 – 22 ]. Solely Spreckley and Boyd [ 22 ] concluded that the interventions are not superior to standard care.

The meta-analyses have some methodological problems, such as a risk for biased effect sizes, the inclusion of studies without an appropriate control group or the use of fixed-effect models. Specifically, the use of uncontrolled pre-post-comparisons to calculate an effect size (as used in [ 8 , 17 , 18 , 21 ]) is susceptible for threats of validity and may lead to overestimation of the effect size [ 16 ]. Effect sizes can also be biased, if they are not standardized (as seen in [ 21 ]). The use of fixed-effect models while including studies with more than one control group (e.g., [ 24 ]) is problematic because these models do not control for the dependence of effect sizes (as seen in [ 16 ]). Finally, an underestimation of effect sizes can occur from primary studies that compare two intensive ABA-based treatments, like the study from Sallows and Graupner [ 25 ] or the study by Smith, Groen and Wynn [ 26 ] (as seen in [ 14 , 19 , 22 ]). Considering the limitations of previous meta-analyses, applying a more rigorous meta-analytic methodology appears warranted.

Adding to this, the methodological quality of many primary studies investigating interventions for autistic children is low [ 14 , 27 ]. This could result in inflated effect sizes and, thus, bias the meta-analytic conclusions drawn from those studies. Some (e.g., [ 14 , 19 , 27 ]) but not all previous meta-analyses have considered the risk of bias of primary studies in order to assess the certainty of the results. However, this procedure is essential when conducting a meta-analysis in a research field with many primary studies that are limited in their methodological quality.

Further, several studies (primary studies and meta-analyses) have pointed towards potential factors, that might moderate the impact of comprehensive ABA-based treatments on developmental outcomes. Potential moderators are especially relevant for the improvement and personalization of treatment methods. Possible moderators are higher intellectual functioning (e.g., [ 28 ]), higher language abilities [ 27 ], more adaptive behavior, and less severe psychopathology at intake [ 28 , 29 , 30 , 31 ]. Some studies discuss age as a potential moderator of the effectiveness of comprehensive ABA-based interventions (e.g., [ 27 , 29 , 30 , 31 , 32 ]). Furthermore, treatment intensity and duration, cumulative intervention intensity as well as parental training and participation (as therapists) could impact the outcome [ 17 , 20 , 27 , 31 , 32 , 33 , 34 ]. A recent meta-analysis on the effects of early interventions on social communication in autistic children [ 35 ] showed that interventions with parental participation had slightly smaller effect sizes than interventions provided by clinicians only. This result contrasts earlier results [ 36 ] in which interventions provided by parents and clinicians seemed to improve the effect of treatment compared to parent-only or clinician-only interventions. Further, there is evidence that maternal involvement in comprehensive ABA-based treatments is connected to mothers’ personal strain [ 37 ]. That is, the necessity of parental participation is unclear and might be associated with negative consequences for the parents. Overall, findings from meta-analyses [ 8 , 17 , 20 ] as well as findings in primary literature regarding potential moderators are heterogeneous and thus rather inconclusive. For example, Makrygianni and Reed [ 18 ] showed that treatment intensity is correlated with treatment gains in intellectual functioning and adaptive behavior, whereas Reichow and Wolery [ 20 ] did not find evidence for any impact of treatment intensity or duration.

In the current meta-analysis, we first aim to replicate findings of previous studies regarding impacts of comprehensive ABA-based interventions on adaptive behavior, intellectual functioning, language abilities, and symptom severity, applying a more rigorous methodology. Based on the results of preceding meta-analyses, we assume that comprehensive ABA-based (vs. control group) interventions improve adaptive behavior, intellectual functioning, language abilities (expression and comprehension), and symptom severity.

Second, we aim to investigate possible moderators of treatment outcomes. We hypothesize that comprehensive ABA-based interventions are more effective for younger children (e.g., [ 32 ]), with fewer impairments in adaptive behavior (e.g., [ 28 ]), intellectual functioning (e.g., [ 28 ]), language abilities (e.g., [ 31 ]), and with lower symptom severity (e.g., [ 30 ]) at intake. Additionally, we assume that parental participation (e.g., [ 36 ]), longer treatment duration (e.g., [ 34 ]), higher treatment intensity (e.g., [ 17 ]), and higher cumulative intervention intensity (e.g., [ 32 ]) increase the effectiveness of comprehensive ABA-based interventions. Finally, we hypothesize that the impact of treatment duration and (cumulative) intensity is higher in younger children (based on the findings of [ 32 ]).

Third, we aim to investigate whether this kind of intervention has an impact on parental stress. Parents of children with ASD experience greater stress than parents of typically developing children or children with other disabilities [ 38 ]. Thus, we hypothesize that comprehensive ABA-based interventions might reduce parental stress by reducing children’s symptom severity. But, as mentioned above, involvement in comprehensive ABA-based interventions can decrease parental well-being [ 37 ]. Accordingly, parental stress might be increased due to the high demands of comprehensive ABA-based interventions (for example, delivering treatment to the child in “almost all of the subjects' waking hours, 365 days a year” [ 39 ]).

Eligibility criteria

Studies included in this meta-analysis had to meet the following criteria: 1) ASD was diagnosed according to the International Statistical Classification of Diseases and Related Health Problems (ICD 10) or DSM IV criteria; 2) studies provided a control group (i.e. randomized controlled trials (RCTs), quasi-randomized trials and controlled clinical trials); 3) treatment groups had at least five participants; 4) at least one group had to receive a comprehensive ABA-based intervention, as defined previously, for more than 10 h per week Footnote 1 ; 5) control groups received treatment as usual (TAU) or an alternative active intervention (no comprehensive ABA-based intervention with more than 10 h of treatment per week); 6) at least one child-related outcome (adaptive behavior, intellectual functioning, language abilities or symptom severity) was reported; 7) mean and standard deviation for each outcome were reported, computable or provided by the authors of the study; 8) the study was published in English or German in a peer-reviewed journal or as part of a doctoral dissertation. We did not include retrospective or epidemiological studies, merely qualitative studies or studies without standardized outcome measures. Additionally, although many studies in the field of comprehensive ABA-based interventions for autistic children are single case experimental studies [e.g., 12], we decided to only include studies with a controlled design in order to reduce heterogeneity of included studies and, thus, promoting the validity of the integrated results.

Search methods for identification of studies

We conducted a literature search in the databases Medline, Psyndex, PsycInfo, and PsycArticles from January 1 2018 until March 6 2018 and updated this search from March 5 2020 until March 9 2020. Additionally, we searched Google Scholar and considered relevant studies from reference lists of preceding meta-analyses [ 8 , 15 – 22 ]. We did not restrict study obtainment by publishing date. We used following search terms (English and German equivalents): ASD , autism , or autism spectrum disorder AND EIBI , ABA , early intensive behavio(u)r intervention , applied behavio(u)r analysis , comprehensive ABA , early intensive behavio(u)r treatment , UCLA-model , Lovaas , intensive or behavio(u)r training . Our search term also included Early Start Denver Model and pivotal response training to broaden the results of our literature search. However, studies that only focused on those (NDBI) interventions were not included in our analysis. The full search strategy is listed in the supplementary material A.

Data collection and quality assessment

Title and abstract of all distinct reports were screened, and all potentially applicable studies were coded. A second independent rater assessed and coded nine (12%) of the 75 potentially applicable studies. The inter-rater agreement for eligibility was low (Cohen’s κ = 0.4), so discrepancies were discussed among the authors and studies in question were reassessed. Additionally, eight more studies were assessed by the second rater, so that in total 22% of studies were rated by two independent raters. After discussion, reassessment and additional coding, inter-rater agreement for study eligibility reached Cohen’s κ = 1.0. Both raters used a data collecting form (supplementary material A). We calculated inter-rater agreement before and after the discussion for all relevant outcomes and moderators (see supplementary material B). Please note, that the moderators were only rated after discussion and reassessment.

To assess risk of bias for each study, we used the “Cochrane Collaboration’s tool for assessing risk of bias” [ 23 ]. A brief description of this tool can be seen in supplementary material C.

Statistical analyses

We calculated standardized mean differences (SMDs) between groups as effect size for each outcome as recommended by Viechtbauer [ 40 ] for continuous data and measures with different scales and corrected SMDs for bias resulting from small sample sizes [ 41 ]. As recommended by the Cochrane handbook of systematic reviews [ 23 ], we used post-treatment comparisons in the effect size calculation. Table 1 provides a summary of formulas used in this meta-analysis.

In studies with multiple intervention groups, we included the comparison between the two most relevant intervention groups only to prevent an uneven weighting of the sample used in those comparisons. We investigated heterogeneity of the included studies by computing Q statistics, assessing variation of the true effect sizes between studies through \({\upsigma }_{B}^{2}\) , and calculating I 2 . We evaluated the risk for publication bias by a visual inspection and a test of funnel plot asymmetry, according to Egger and colleagues [ 42 ]. We conducted this test only for outcomes with more than 10 effect sizes and with univariate models, as recommended by Sterne and colleagues [ 43 ].

We calculated a random effects model because we assumed varying true effect sizes due to differences between specific treatments. To address the fact that most outcomes were measured in different dimensions, we used a multilevel meta-analysis model. We computed this meta-analysis using the R-package “metafor” (package version: 1.9–4, R-studio version: 1.1.447) [ 40 , 44 ].

We conducted moderator analyses with children’s age and abilities (intellectual functioning, adaptive behavior, language before treatment), treatment intensity, and duration. Further, we computed an additional variable called cumulative intervention intensity (hours/week × 4,33 × duration in months). Because the number of studies reporting symptom severity at intake was too low and treatment was delivered by parents and therapists in all studies, we had to drop the moderators symptom severity and parental participation from the analyses.

Study and sample characteristics

Fourteen studies from the initial literature search met the eligibility criteria. Two of those studies were excluded because they assessed follow-up samples of other included studies [ 45 , 46 ]. Thereby we avoided including the same sample multiple times. Furthermore, we were not able to obtain the pre-treatment measurement for one study [ 47 ]. The update of the literature search in 2020 did not reveal additional eligible studies. Thus, we included 11 studies with 632 participants in our meta-analysis. Figure  1 illustrates the study selection  process.

Flow chart of study obtainment process

Most included studies were clinical controlled trials with a quasi-experimental design. Only the study from Shawler [ 48 ] was a RCT. As Table 2 shows, eight out of 11 studies, compared comprehensive ABA based treatments to treatment as usual (TAU). Specifically, TAU contained eclectic treatment strategies combining a variety of interventions mostly from Treatment and Education of Autistic and Related Communication Handicapped Children principles (TEACCH principles, [ 58 ]), Picture Exchange Communication System (PECS, [ 59 ]), ABA-based interventions, Makaton [ 60 ], and speech and occupational therapies. No study provided a quantification of the extent to which each intervention was applied. One study [ 24 ] included two control groups. We only considered one control group, specifically the eclectic educational program, which was more similar to the TAU control groups.

One study compared an ABA-based treatment to another active treatment [ 53 ]. However, other than the studies by Sallows and Graupner [ 25 ] and Smith and colleagues [ 26 ], this study did not use intensive, comprehensive ABA-based treatment in the control group, but instead used low-intensity, targeted ABA-based training. Finally, one study used a waitlist control design. On average, comprehensive ABA-based interventions had an intensity of 21.84 h per week ( SD  = 5.90, ranging from 13.6 to 32.4 h/week) and the control group treatments 17.19 h per week ( SD  = 10.83, ranging from 0 to 29.8 h/week). For a detailed study and participant description see Table 2 .

Outcome measures

The outcomes were assessed with many different measures (see supplementary material D for a complete list of all instruments). The most frequently used instruments will be described in the following. Adaptive behavior was mostly measured with the Vineland Adaptive Behavior Scale (VABS I or II) [ 61 , 62 ] on the four scales communication, socialization, daily living, and motor skills. To assess intellectual functioning, most studies administered the Mullen Scales of Early Learning (MSEL) [ 63 ], the Bayley Scales of Infant Development (BSID) [ 64 , 65 ], the Stanford-Binet Intelligence Scale: Fourth Edition (SB:FE) [ 66 ], the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-R) [ 67 ], or the Wechsler Intelligence Scale for Children (WISC-R, WISC-III) [ 68 , 69 ] . The MSEL and BSID mainly examine motor skills, language, and behavioral abilities, the WPPSI-R, SB:FE, and WISC-R rather assess verbal comprehension, reasoning, knowledge, and memory. The Reynell Developmental Language Scale (RDLS, RDLS III) [ 70 , 71 ] was used to measure language comprehension and expression in most studies. Symptom severity was assessed by the Autism Diagnostic Observation Schedule (ADOS) [ 72 ], the Autism Diagnostic Interview – Revised (ADI-R) [ 73 ], or the Autism Screening Questionnaire (ASQ) [ 74 ]. ADOS is based on ratings of an assessor, ADI-R is a structured parent interview and the ASQ is a questionnaire for parents. Parental stress was measured with the self-report questionnaires Parenting Stress Index (PSI) [ 75 ] and the Parent and Family Problems subscale of the Questionnaire on Resources and Stress–Friedrich short form (QRS-F) [ 76 ]. Studies that applied more than one measure for a construct, provided a mean value for that construct across all instruments (e.g., on the IQ scale), which was used for the effect size calculation.

Risk of bias

Table 3 displays an overview of risk of bias in each study.

Selection bias (sequence generation and allocation sequence concealment)

One included study used a randomized procedure to assign participants to groups [ 48 ]. All other studies used quasi-experimental designs and thus had a higher risk of selection bias. However, Shawler [ 48 ] did not provide enough information about the randomization process and allocation concealment, so the real risk of selection bias remains unclear for this study.

Performance and detection bias (Masking of participants and personnel/ outcome assessment)

Participants (and their parents) as well as personnel were not masked in any study. Outcome assessors were truly masked in one study [ 49 ]. In one study [ 51 ], only 60% of cases were evaluated by a masked assessor but they controlled for the other 40% and found no evidence of bias. Thus, we labeled this study with a low risk of detection bias.

Attrition bias (incomplete data)

The risk of incomplete data and therefore of attrition bias was low in four studies [ 48 , 49 , 54 , 55 ]. Four studies did not report how many participants were reassessed after the intervention. Therefore, risk of bias is unclear [ 51 , 52 , 56 , 57 ]. High risk for attrition bias emerges from four studies. In one study [ 50 ], data for the post-treatment-measurement was available for only 25% (adaptive behavior) or 22% (symptom severity) of children. Fernell and colleagues [ 53 ] reported that 10 out of 208 children were not assessed after the intervention. Several other children participated only in some of the required outcome measurements. Neither reasons for this lack of participation nor the amount of withdrawals for each group were stated. In the study of Howard and colleagues [ 24 ], 22% of participants (17 out of 78) dropped out for unknown reasons. Additionally, some of the remaining children did not complete all outcome measurements.

Reporting bias (selective reporting)

We did not find selective reporting in most studies. Eikeseth and colleagues [ 50 ] reported symptom severity for the treatment group only and did not conduct a between-group comparison for this outcome. Therefore, this study might be affected by reporting bias.

Other risks of bias

Six studies reported that the control group received or might have received some treatment based on ABA-techniques [ 24 , 49 – 53 ]. Furthermore, intervention groups differed substantially at baseline in five studies [ 24 , 49 , 53 , 54 , 56 ]. In studies by Fernell and colleagues [ 53 ], Howard and colleagues [ 24 ], and Remington and colleagues [ 56 ], children in the treatment group were significantly younger than children in the control group. Magiati and colleagues [ 24 , 54 ] reported that children in treatment group scored higher in intellectual functioning (83 vs. 62.5 [IQ scale], p  = 0.04), in the composite score of adaptive behavior (60.3 vs. 56.6 [standard score], p  = 0.05) and in the socialization subscale of adaptive behavior (59.6 vs. 55.4 [standard score], p  = 0.04) at intake.

Effects of intervention

Adaptive behavior.

For this analysis, we included 28 comparisons from nine studies with 547 participants at pre-treatment measurement. Figure  2 illustrates evidence that comprehensive ABA-based treatments improve adaptive behavior more strongly compared to TAU, minimal or no treatment (SMD = 0.37, 95% confidence interval (CI) [0.03; 0.70]). We found substantial variance between studies ( \({\upsigma }_{B}^{2}\) = 0.24) but no variance within the studies ( \({\upsigma }_{W}^{2}\) = 0.00). The tests for heterogeneity indicated substantial heterogeneity ( Q ( df  = 27) = 106.18, p  < 0.001; I 2  = 72.95). Statistical testing ( z  = 3.36, p  < 0.001) and funnel plot inspection (Fig.  7 ) indicated a publication bias.

Forrest plot of pooled SMD in post-treatment scores in adaptive behavior

Intellectual functioning

Eight studies assessed intellectual functioning ( N  = 293 at pre-treatment assessment). As displayed in Fig.  3 , participants in treatment groups show significantly more improvement in intellectual functioning than participants in control groups ( SMD  = 0.51, 95% CI [0.09, 0.92]). There is considerable variance between studies ( \({\upsigma }_{B}^{2}\) = 0.22). The Q statistic, Q (7) = 17.87, p  = 0.013; I 2  = 63.59%, indicates heterogeneity between studies. Visual inspection of a funnel plot does not lead to the assumption of publication bias (Fig.  7 ).

Forrest plot of pooled SMD in post-treatment scores in intellectual functioning

Language abilities

We did not find a significant difference in post-treatment scores between treatment and control group regarding language abilities ( SMD  = 0.30, 95% CI [-0.13; 0.72]; Fig.  4 ). We included five studies from which we calculated nine effect sizes ( N  = 210 at pre-treatment assessment). Analyses show no variance between the dimensions of language abilities (expression and comprehension; \({\upsigma }_{W}^{2}\) = 0.00). Again, there is substantial variance between studies ( \({\upsigma }_{B}^{2}\) = 0.17) as well as substantial heterogeneity Q (8) = 16.81, p  = 0.03; I 2  = 61.94%. Visual inspection of the funnel plot indicates no funnel plot asymmetry (see Fig.  7 ).

Forrest plot of pooled SMD in post-treatment scores in language abilities

Symptom severity

There is no strong evidence for lower levels of symptom severity in children receiving comprehensive ABA-based treatments compared to children in other treatment conditions after intervention ( SMD  = -0.26, 95% CI [-0.60, 0.07]; see Fig.  5 ). This analysis is based on four comparisons from three different studies with 107 participants at pre-treatment assessment. There is neither variance between dimensions (mother’s and father’s rating of child’s symptoms; \({\upsigma }_{B}^{2}\) = 0.00) nor between studies ( \({\upsigma }_{B}^{2}\) = 0.00). Based on the Q statistic, we assume no substantial heterogeneity, Q (3) = 2.39, p  = 0.50; I 2  = 0.00%. We found no evidence for funnel plot asymmetry (see Fig.  7 ), but the low number of studies limits a proper interpretation of the funnel plot.

Forrest plot of pooled SMD in post-treatment scores in symptom severity

Parental stress

For this analysis, five comparisons from three studies with 128 participants at pre-treatment assessment were included. As Fig.  6 displays, there is no evidence for a substantial difference in stress ratings between parents in each intervention condition ( SMD  = 0.38, 95% CI [-0.26, 1.01]).

Forrest plot of pooled SMD in post-treatment scores in parental stress

There is no variance between dimensions of the construct (mother’s and father’s stress rating; \({\upsigma }_{W}^{2}\) = 0.00) but substantial variance between studies ( \({\upsigma }_{B}^{2}\) = 0.19). The Q statistic indicates no heterogeneity, Q (4) = 5.23, p  = 0.26. The calculation of I 2 resulted in I 2  = 52.24%. The funnel plot does not hint toward publication bias (see Fig.  7 ). Again, validity of this plot is limited, because of the low number of included studies.

Funnel plots used for publication bias assessment

Moderator analyses

Table 4  shows the results of moderator analyses. Due to the small number of eligible studies, we were not able to conduct all planned moderator analyses. We found a significant influence of language abilities (comprehension) at intake on the effect size in intellectual functioning and adaptive behavior. Further, the moderator analyses indicate that abilities of language expression at intake influence the effect size in intellectual functioning and language abilities. Additionally, we inspected possible interactions between treatment duration, intensity as well as total amount of time spent in comprehensive ABA-based interventions and age. Evaluating tests of moderators on the basis of Q statistics indicate an interaction between age and treatment intensity for adaptive behavior, which indicates that the influence of treatment intensity on post-treatment adaptive behavior decreases with older age ( β  =  - 0.01, [-0.01, -0.00], Q M (3) = 74.45, p  < 0.001). The validity of all described examinations is restricted due to the small number of eligible studies. Therefore, results should have no more than an indicative value.

Table 5 displays that some variables considered as moderators are highly correlated. Therefore, it would be necessary to conduct moderator analyses controlling for the influence of other potential moderators. The low number of included studies prevents such analyses. Still, the high correlations have to be kept in mind when drawing conclusions from those moderator analyses.

The current meta-analysis investigated the effect of comprehensive, intensive interventions based on Applied Behavior Analysis (ABA) for ASD versus treatment as usual (TAU), minimal or no treatment on adaptive behavior, intellectual functioning, language abilities, symptom severity, and parental stress. Additionally, the current meta-analysis focused on the potential moderating influence of treatment and demographic characteristics while updating previous meta-analyses and overcoming their methodological limitations. Most studies (with the exception of Shawler [ 48 ] and Molnár and Eldevik [ 55 ]) included in our meta-analysis were also included in previous meta-analysis, however, no meta-analysis focused on all eleven studies. Our meta-analysis revealed that most studies that were eligible to be included in this review were of low methodological quality. Therefore, the results of our meta-analysis might be affected by the high risk of bias in the included studies. We discuss this issue in greater detail in the limitations section of our discussion.

The results based on post-treatment comparison effect sizes reveal that comprehensive ABA-based interventions (compared to TAU, minimal or no treatment) have a medium effect on intellectual functioning (8 effect sizes) and small effect on adaptive behavior (28 effect sizes), according to Cohen’s conventions [ 77 ]. Thus, children who receive comprehensive ABA-based treatments tend to show stronger improvements in intellectual functioning and adaptive behavior than children receiving TAU, minimal or no treatment, which is in line with previous meta-analyses (e.g., [ 8 , 12 , 14 ]). Our results did not indicate differences between treatment and control group in post-treatment scores for language abilities, symptom severity or parental stress. The current analyses revealed overall smaller effect sizes than most previous meta-analyses (e.g., [ 8 , 16 – 18 ]). This is most probable caused by the more conservative inclusion criteria. In contrast, Sandbank et al. [ 12 ] reported a smaller effect size (estimated summary effects) for behavioral interventions on intellectual functioning (effect size = 0.29* vs. 0.51*, study N  = 21 vs. 9) and a similar effect size for adaptive behavior (effect size = 0.38* vs. 0.37*, study N  = 21 vs. 9). However, in their comprehensive study on seven different types of early interventions for ASD, they applied a broader definition of behavioral interventions and assigned more studies to this intervention type, accordingly (besides EIBI, the Lovaas Model, and Verbal Behavior also studies on PECS, Discrete Trial Training, and Autism Partnership). Opposed to Virués-Ortega [ 8 ] and Reichow and Wolery [ 20 ], we found no evidence for publication bias for intellectual functioning and language abilities. However, our analyses indicated publication bias for adaptive behavior.

Five studies were included to investigate the effects on symptom severity and parental stress. The analyses also did not reveal effects of comprehensive ABA-based treatments versus control group treatments indicating that none of the treatments are superior to each other in reducing symptom severity and parental stress. The lack of evidence for a reduction in symptom severity due to comprehensive ABA-based interventions beyond the effect of other treatments found in this study is in line with findings in the updated review of Reichow and colleagues [ 14 ] but different from Sandbank et al.’s [ 12 ] findings, who reported an effect size of 0.45 [0.26; 0.68].

To our knowledge, no other meta-analysis besides our own has calculated an effect size for parental stress yet. Even though Schwichtenberg and Poehlmann [ 37 ] found that parental involvement in comprehensive ABA-based interventions increased maternal strain, we did not find evidence for impact of comprehensive ABA-based interventions on parental stress beyond the impact of treatment as usual, no or minimum treatment. However, because of the small number of studies included in these analyses a negative or non-detected positive effect for parental stress and symptom severity has to be considered. Therefore, a definite conclusion would be premature.

As outlined above, previous research regarding moderating variables in comprehensive ABA-based treatments is inconsistent. Because of several aspects discussed in the limitation section, results of moderator analyses in this study have to be interpreted with caution. The current moderator analyses indicated that higher language abilities at intake are beneficial for gains in intellectual functioning and adaptive behavior. This finding supports findings of previous primary studies (e.g., [ 31 ]) and meta-analyses (e.g., [ 27 ]). The interaction between age and treatment intensity for adaptive behavior indicates a decreasing influence of treatment intensity on adaptive behavior with older age. A replication of our results is needed, before sound conclusions can be drawn. However, if the finding on a decreased influence of treatment intensity on adaptive behavior with older age replicated, this might inform decisions on treatment indications.

Limitations

Primary studies are the basis of every meta-analysis. The studies included in the present meta-analysis investigated children with a mean age between 2.2 and 5.5 years at intake, mostly without comorbidities and mostly from western countries, limiting generalization of results to these demographic characteristics. Another source of bias could be parents’ acceptance of treatment, since group assignment was based on parental preference in most studies. Besides limitations regarding participant characteristics, included primary studies and, thus, this meta-analysis are limited by a very low quality of evidence determined with the approach from Higgins and Green [ 23 ]. Concerns regarding the influence of selection and performance biases are raised by the facts that no study reported an adequate randomization procedure, allocation was not concealed, and personnel and participants were not masked. However, not masking personnel and participants is a limitation that can hardly be overcome in future studies, since it is incompatible with training parents and personnel to apply intensive ABA-based treatments. Another source of bias lies within the control groups, which are only vaguely defined and varied a lot in their intensity ( M  = 17.19 h/week, SD  = 10.83). Thus, they are hardly comparable and prone to contamination. For instance, if TAU groups applied ABA-based methods to a large extent (e.g., 9 h per week) without reporting this clearly, the effect size for comprehensive, intensive ABA-based interventions could be underestimated. Future studies should precisely report which interventions were delivered to which extent. Several studies reported baseline imbalances between groups, which indicates possible confounding variables. Furthermore, some outcome measures, for example VABS or ASQ, are based on parental reporting. These reports might be biased since group assignment was based on parental preference. The low quality of evidence appears to be a common problem within the research on treatment for autistic children (see [ 14 ] and [ 12 ]). This limits the informative value of meta-analyses in this field. Therefore, Sandbank and colleagues [ 12 ] recommend several approaches that could help to increase the methodological quality of studies with autistic children. For example, they recommend that outcomes are assessed by trained assessors and not parents or teachers. We support the statement of Sandbank and colleagues that researchers should continue to strive to conduct high-quality studies. Another starting point to improve methodological quality, is the assessment of intellectual functioning (a core developmental outcome). Most studies used instruments measuring IQ with verbal tasks [ 78 ]. Therefore, better scoring in those instruments might also reflect improved language abilities. Additionally, several studies used more than one instrument and calculated average IQ scores over all instruments. This would only be legitimate, if all used instruments measured the exact same construct — an assumption none of the studies validated. It can be difficult to find one instrument that is valid for all study participants, as they vary regarding age and intellectual impairment. However, we suggest that future studies may use as few instruments as possible to ensure comparability between participants. Finally, it has to be considered, that young autistic children often underperform in tests on intellectual functioning, for example, due to motivational reasons. Another limitation is, that some relevant studies could not be included because required data were not reported and could not be obtained by the authors.

An important limitation of our study is the effect size selection. As described above, it is recommended by the Cochrane Handbook [ 23 ] to use post-treatment comparisons, if standard deviations for change scores are not reported in primary studies. However, it is also stated that this procedure should be unproblematic for randomized trials. It should be noted, that effect sizes based on post-treatment comparisons could be biased due to baseline differences in treatment and control group if most primary studies applied a quasi-experimental design. The results of the moderator analyses may be interpreted as preliminary, as the number of primary studies including these moderators was low. Especially symptom severity at intake was assessed rarely and with different measures in primary studies. Most measures were not originally designed to quantify symptom severity, even though higher scores in ADI-R and ADOS indicate more deficits [ 74 , 79 ]. The guidelines for the diagnostics of ASD from the Association of the Scientific Medical Societies (AMWF) recommend to use the ADI-R and the ADOS in order to support the diagnostic process in children with ASD (for the detailed recommendation see [ 80 ]). If future studies endorse this recommendation, they should report the results of those assessments. Nevertheless, the development of a reliable instrument for the assessment of symptom severity in children with ASD would be preferable. Furthermore, the number of studies including parental stress was too low to conduct moderator analyses. To sum up, results from our moderator analyses, especially the examination of interactions between moderators, are merely indicative at the time being and have to be replicated. Additionally, further and more complex analyses have to be conducted, for example to account for the correlation between investigated variables. Therefore, we conclude that moderators and their interactions cannot be investigated properly until more studies contribute to the analysis.

This study excluded single case experimental design studies, even though they are commonly administered in the research on treatments for autistic children (e.g., [ 12 ]). However, while we think that single case designs are important, since there is a large heterogeneity in autistic individuals, which is better addressed in single case studies, we also agree with Sandbank and colleagues [ 12 ], that studies with a controlled design are needed to explore the generalizability of the effects of comprehensive ABA-based interventions. Next to the concerns expressed in Sandbank et al. [ 12 ], we believe that the inclusion of single case studies in our meta-analysis would have added to the already high heterogeneity in studies included in our meta-analysis, thus further limiting the conclusiveness of our results.

Importantly, besides the understanding of ASD as a neurodevelopmental disorder, as can be found in the ICD or DSM, autism is also conceptualized in a neurodiversity framework by many autistic individuals, researchers and clinicians, namely as a natural variation of neurological diversity [e.g., 81 ]. It is being discussed whether early interventions in general are at all compatible in this framework, as they are usually focused on curing or reducing impairments rather than on the strengths associated with neurodiversity [e.g., 82 , 83 ]. An in-depth discussion of the conceptualization of autism as well as ethical considerations regarding comprehensive ABA-based interventions in children with ASD is limited in this meta-analysis because it is beyond the scope. Nevertheless, 1) addressing concerns which are held against comprehensive ABA-based treatments and investigating undesirable side effects in behavioral treatments, as recommended by the National Institute for Health and Care Excellence [ 84 ], as well as 2) considering changes in comprehensive ABA-based interventions acknowledging the neurodiversity framework appear important to improve the support for autistic children and their families.

Conclusions

Several meta-analyses, including the current study, revealed evidence for a medium effect of comprehensive ABA-based interventions (vs. treatment as usual, minimal or no treatment) on intellectual functioning and adaptive behavior. However, the current meta-analysis did not revealed support for effects on language abilities, symptom severity, and parental stress beyond the control group treatments. Methodological limitations of primary studies and, thus, this meta-analysis may bias these results (e.g., low number of studies for analysis on symptom severity). However, the effect of comprehensive ABA-based interventions on core features of ASD may be comparable to the effects of the control group treatments. As comprehensive ABA-based interventions investigated in this meta-analysis contained more treatment hours (ABA 21.85 h/week, SD  = 5.90 vs. CG 17.19 h/week, SD  = 10.82), one may conclude that they are overly extensive and not justified. But then, if comprehensive ABA-based treatments (compared to no or minimal treatment or TAU) lead to higher levels of adaptive behavior and intellectual functioning as our study indicates, they would decrease the differences between the developmental and actual age of children on the autistic spectrum in these areas. Improvements of this kind can make major differences in the daily life of the children and their families.

Still, to answer the question, whether comprehensive ABA-based interventions are valid treatments for ASD, to full extent, more methodological sound studies are needed. Thus, robust conclusions on the effectiveness are still limited by a low number and rather low quality of primary studies. This applies also to the moderating influence of treatment characteristics, such as treatment intensity, and child characteristics, such as age. Conclusive knowledge in regard to effectiveness and moderators would help professionals to decide about indication of different treatment options and would help parents of children with ASD to make an informed decision. Other statistical approaches, e.g. growth curve analyses as seen in the study by Tiura and colleagues [ 31 ], might help to develop personalized treatment options [ 85 ]. Additionally, future research may aim to overcome limitations of previous studies. For example, the (further) development and evaluation of diagnostic procedures in children with ASD is sorely needed [ 80 ]. This would lower the risk for biases in meta-analytic methods. Further, the ethical concerns for RCTs on ASD treatment, namely the concern that critical developmental stages of the children might pass during the treatment in potentially non-profitable treatment groups, may be addressed by either comparing two potentially helpful interventions [ 78 ] or using new methodological approaches, such as adaptive rolling designs [ 86 ].

Availability of data and materials

The datasets generated and/or analyzed during the current study are available in the OSF repository, https://osf.io/wfgu3/ .

In line with Virués-Ortega [ 8 ], we chose to set the limit for intensity lower than it should be according to the definition of ABA-based treatments. Thus, we were able to achieve more variety in treatment intensity. This was necessary to conduct a moderator analysis considering treatment intensity.

Abbreviations

• Applied Behavior Analysis

Applied Behavior Analysis—Verbal Behavior Approach

Autism Diagnostic Interview – Revised

Autism Diagnostic Observation Schedule

Association of the Scientific Medical Societies

American Psychiatric Association

• Autism Spectrum Disorder

Autism Screening Questionnaire

Bayley Scales of Infant Development

Confidence Interval

Diagnostic and Statistical Manual of Mental Disorders

• Early Intensive Behavioral Interventions

Early Start Denver Model

International Statistical Classification of Diseases and Related Health Problems

Naturalistic Developmental Behavioral Interventions

National Institute for Health and Care Excellence

Picture Exchange Communication System

Parenting Stress Index

Questionnaire on Resources and Stress–Friedrich Short Form

Randomized Controlled Trial

Reynell Developmental Language Scale

Stanford-Binet Intelligence Scale: Fourth Edition

Standardized Mean Difference

Treatment as Usual

Treatment and Education of Autistic and Related Communication Handicapped Children

Vineland Adaptive Behavior Scale

Wechsler Intelligence Scale for Children

Wechsler Preschool and Primary Scale of Intelligence

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We thank Isabel Dziobek for critically reviewing a draft of the manuscript. Correspondence concerning this article should be addressed to Anne Möllmann, University of Bremen, Institute of Psychology, Clinical Psychology and Psychotherapy, Grazer Str. 6, D – 28359 Bremen, Germany, [email protected]

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Eckes, T., Buhlmann, U., Holling, HD. et al. Comprehensive ABA-based interventions in the treatment of children with autism spectrum disorder – a meta-analysis. BMC Psychiatry 23 , 133 (2023). https://doi.org/10.1186/s12888-022-04412-1

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A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report

• Juliana Andrea Ponton   ORCID: orcid.org/0000-0002-7405-1797 1 ,
• Kim Smyth 2 ,
• Elias Soumbasis 1 ,
• Sergio Andres Llanos 1 ,
• Mark Lewis 1 ,
• Wilhelm August Meerholz 1 &
• Robert Lawrence Tanguay 1  

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The pharmacological treatment for autism spectrum disorders is often poorly tolerated and has traditionally targeted associated conditions, with limited benefit for the core social deficits. We describe the novel use of a cannabidiol-based extract that incidentally improved core social deficits and overall functioning in a patient with autism spectrum disorder, at a lower dose than has been previously reported in autism spectrum disorder.

Case presentation

The parents of a 15-year-old boy, of South African descent, with autism spectrum disorder, selective mutism, anxiety, and controlled epilepsy, consulted a medical cannabis physician to trial cannabis extract to replace seizure medications. Incidentally, at a very low cannabidiol-based extract dose, he experienced unanticipated positive effects on behavioral symptoms and core social deficits.

This case report provides evidence that a lower than previously reported dose of a phytocannabinoid in the form of a cannabidiol-based extract may be capable of aiding in autism spectrum disorder-related behavioral symptoms, core social communication abilities, and comorbid anxiety, sleep difficulties, and weight control. Further research is needed to elucidate the clinical role and underlying biological mechanisms of action of cannabidiol-based extract in patients with autism spectrum disorder.

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Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is characterized by deficits in two major domains: restrictive, repetitive patterns of behavior, interests, or activities; and deficits in social communication and interaction [ 1 , 2 ]. ASD is associated with a higher incidence of comorbid conditions including attention deficit hyperactivity disorder, anxiety, gastrointestinal disturbances, motor impairments, and epilepsy. Symptoms appear in early childhood and vary in severity leading to a broad range of clinical manifestations [ 2 ].

The pathogenesis of ASD is not completely understood [ 3 ]. Given its complexity and diverse clinical manifestations, it is believed that the etiopathogenesis of ASD is a combination of genetic, epigenetic, neurobiological, diet, and other environmental factors [ 4 ]. Hundreds of genes ( NLGN , SHANK3 , ZNF8034A, and UNC13A) [ 5 , 6 ] have been linked to ASD, most of which are closely related to the development of the nervous system [ 1 ].

There is a myriad of theories that attempt to explain the occurrence of ASD [ 1 , 3 , 7 ], although the two most accepted are impaired synaptic transmission and disruption of neural connectivity. The endocannabinoid system (ECS) has attracted considerable attention as a potential contributor to ASD, as the development of the ECS is essential for regulating synaptic function by inhibiting the release of neurotransmitters from presynaptic neurons [ 1 ].

The management of ASD requires individualized, comprehensive treatment. Non-psychopharmacologic interventions (for example, cognitive behavioral therapy) modify disruptive behaviors and improve social communication skills with varying degrees of success. Traditional psychopharmacologic medications target specific ASD core behaviors (for example, repetitive behaviors) and associated behaviors (for example, hyperactivity, aggression, anxiety, and sleep disturbances), but do not treat core social communication deficits [ 8 , 9 ]. These medications are well known for their substantial side effects. For example, aripiprazole and risperidone, the only two medications approved by the US Food and Drug Administration (FDA) to treat irritability and agitation in ASD, frequently cause somnolence, increased appetite, and weight gain [ 10 ]. No other medication has been approved for management of behavioral and/or core ASD symptoms. Challenges with these traditional treatment approaches include barriers to access (economical, geographic), lack of efficacy, and undesirable side effects, which have led many families to seek complementary and alternative medicine (CAM) to augment or replace standard therapy [ 8 ]. One of the newest CAM options now being explored in ASD (and, in fact, the wider medical community) is cannabinoids: for example, cannabidiol-based extract (CBE), which is an extract from the cannabis plant, rich in cannabidiol (CBD) [ 11 ].

Follow-up of these patients must also be individualized as presentation of the disorder is highly variable. There are no validated questionnaires to accurately assess clinical progress, therefore, conducting an objective clinical assessment of related behavioral and core symptoms is challenging. Despite this, there are tools available for characterizing the overall functionality of patients with ASD, for example, Autism Spectrum Quotient (AQ) adults version [ 3 ].

The World Health Organization stated that CBD should not be scheduled with the International Drug Control Conventions because of growing evidence of its medicinal applications [ 12 , 13 ]. It is imperative for health care providers to understand the minutiae of how cannabinoids interact with the human body and the different forms of cannabinoids that are available for medical use (for example, synthetocannabinoids, phytocannabinoids) [ 1 ]. Delta-9-tetrahydrocannabinol (THC) and CBD are the most well-known and studied phytocannabinoids. THC is associated with the impairing psychoactive effects of cannabis, resulting in potentially undesirable side effects (dizziness, anxiety, paranoia, dependency, cognitive impairment, and so on). In contrast, CBD is only minimally psychoactive and not impairing or intoxicating at typically used doses (for example, ≥ 20 mg/kg of CBD referred in the majority of intractable seizures studies) [ 1 , 8 , 10 , 11 ].

A multitude of studies have analyzed the use of high-dose CBD extract (~ 20 mg/kg of weight per dose) in the context of intractable seizure treatment [ 14 , 15 ]. It has been reported that CBD effects are dose-dependent (for example, > 160 mg/day elicits a sedating effect and lower doses have been associated with increased wakefulness) [ 16 ]. A few case reports and observational studies have suggested the safety and efficacy of lower dose CBD, for treating behavioral symptoms in ASD [ 11 , 17 , 18 ]. In a prospective study, 188 patients with ASD were treated with lower to medium doses of phytocannabinoids (from 15 mg of CBD three times a day to 300 mg of CBD three times a day), the majority taking 1:20 CBE: 30% CBD to 1.5% THC [ 19 ]. This study found that cannabis was well tolerated, safe, and effective in relieving certain ASD symptoms. More research is needed to assess the long-term effects of CBD, as well as optimal dosing, formulation, delivery method, and so on to maximize both safety and efficacy.

This case report describes the clinical presentation of a pediatric, overweight patient with ASD, epilepsy, anxiety, insomnia, and social deficits who benefited clinically with even lower doses of CBE (4 mg of CBD and 0.2 mg of THC twice a day) compared to the ones already studied [ 19 ].

A 15-year-old boy, of South African descent, is presented with a long-standing history of social and communicative challenges dating back to early childhood, including difficulties in appropriate use of facial expressions, eye contact, and gestures to regulate social interaction (see Fig. 1 for patient’s timeline). He has a history of difficulty in establishing and maintaining relationships, although he has been able to establish some friendships. His mother notes a history of selective mutism dating back to age 3. He has areas of fixated interests and some ritualized behaviors that on assessment were below the threshold for a diagnosis of obsessive-compulsive disorder. In 2016, he was formally diagnosed as having ASD by a specialized organization in British Columbia (BC), the Interior Health Children’s Assessment Network (IHCAN), with supporting evidence from Autism Diagnostic Interview – Revised (ADI-R) and the Autism Diagnostic Observation Schedule 2 (ADOS-2). He does well academically and there are no cognitive concerns. Sometimes he shows aggressive behaviors towards his mother and other relatives.

Patient’s timeline depicting important dates and events. ACH Alberta Children’s Hospital, ADI-R Autism Diagnostic Interview – Revised, ADOS-2 Autism Diagnostic Observation Schedule 2, ASD autism spectrum disorder, AQ Autism Spectrum Quotient (Adult), BC British Columbia, BMI body mass index (calculated by Du Bois method), CBD cannabidiol, CBE cannabidiol-based extract, CSHQ Children’s Sleep Habits Questionnaire (Abbreviated), CYMH Child and Youth Mental Health, IHCAN Interior Health Children’s Assessment Network, OCD obsessive-compulsive disorder, THC delta-9-tetrahydrocannabinol, upset stomach gastrointestinal side effects, VAS visual analog scale, VPA valproic acid. VAS severity for overall anxiety, social anxiety, aggressiveness and irritability, 0 = least severe, 10 = most severe. VAS for talkativeness, 0 = quiet, 10 = very talkative. VAS for focus, 0 = unfocused, 10 = focused

He was diagnosed as having epilepsy characterized by focal seizures at age 7 at an emergency department service in BC and was subsequently treated by his pediatrician and a pediatric neurologist at the Alberta Children’s Hospital (ACH). He was initially prescribed carbamazepine for seizures which was stopped in 2015 due to side effects (upset stomach), followed by clobazam (stopped in 2016 due to suicidal ideation) and valproic acid (VPA) (stopped in 2017 due to alopecia, tremor, and reflux). The latter also caused a significant weight gain of approximately 13 kg in 1 year, resulting in a calculated body mass index (BMI) with the Du Bois method of 25.5 kg/m 2 . He is currently on lamotrigine for seizures, lorazepam for breakthrough seizures, melatonin for insomnia, riboflavin, ranitidine, magnesium, and orally administered CBE 0.2 mL (4 mg of CBD and 0.1 mg twice a day). No therapy had been tried for behavioral symptoms, although his mother mentioned that VPA and lamotrigine were also prescribed for their effect on mood.

He is currently in psychotherapy at the Child and Youth Mental Health (CYMH) clinic in BC for his selective mutism and anxiety disorder diagnosed by psychiatrists in the same province. He has also had sleep difficulties since 2016. His perinatal history is unremarkable. His birth followed a full-term pregnancy and was uncomplicated except for a required caesarean section due to macrosomia (> 4000 g) and macrocephaly (his mother does not remember the measurement), and subsequent hospitalization for neonatal jaundice. No genetic syndrome was suspected; no genetic testing was ever done. He met expected neurodevelopmental milestones for his age. His mother and grandmother have a history of depression and anxiety. There is other familial history of eating disorders and alcoholism, but no history of genetic syndromes.

In mid-2017, his parents consulted a medical cannabis physician from Caleo Health to assess the suitability of cannabis-based medicines as adjunctive or replacement therapy for seizures. At the time, a physical examination and laboratory findings were normal. A neurologic examination was unremarkable; mental status – awake, alert, cooperative; cranial nerves – normal; motor – normal tone, bulk, strength, and reflexes in upper and lower extremities, proximal and distal, deep tendon reflexes 2+ symmetric. A skin examination was unremarkable, there were no hypopigmented macules, café-au-lait macules, neurofibromas, or axillae ephelides. A long-term (48-hour) electroencephalogram done in 2016 did not record any epileptogenic potentials; magnetic resonance imaging (MRI) showed no intracranial abnormalities and a computed tomography (CT) scan of his head was normal (2015). Laboratory results done mid-2017 were normal: complete blood count and differential, vitamin B12, creatinine, sodium, potassium, calcium, magnesium, total bilirubin, albumin, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, alanine aminotransferase, and triacylglycerol lipase. He had low ferritin (11 μg/L) but normal hemoglobin (159 g/L), due to starting a vegetarian diet, which was followed up by the family physician.

He had not had a clinical seizure in 6 months (last seizure in March 2017). Medications at the time of initiation of CBE were: lamotrigine 200 mg twice a day for seizures, lorazepam 1 mg sublingual (SL)/buccal as necessary, infrequently used for seizures, melatonin 6 mg for sleep initiation, riboflavin 400 mg administered orally once daily, magnesium 1 tablet administered orally once daily, and ranitidine 150 mg twice a day. When asked for symptom severity on a visual analog scale (VAS) (0 = least severe, 10 = most severe), his mother reported overall anxiety, social anxiety, aggressiveness, and irritability severity, at 10/10, 10/10, 6/10, and 9/10, respectively. On VAS to assess for talkativeness (0 = quiet, 10 = very talkative) in social situations, the mother reported 0/10. On VAS for concentration (0 = unfocused, 10 = very focused), 4/10 was reported. In regards to sleep, the mother stated he was sleeping approximately 5 to 6 hours, and was having trouble falling asleep. After the initial assessment, his parents gave consent to start therapy and CBE was prescribed (60 mL bottle of 1:20 CBE – 0.001% THC and 0.02% CBD), from CanniMed, with an olive oil carrier. His parents were instructed to administer 0.1 mL twice a day (2 mg CBD and 0.1 mg THC) and increase by 0.1 mL (2 mg CBD and 0.1 mg THC) per dose if no effects were shown to a maximum of 0.5 mL (10 mg CBD and 0.5 mg THC) per dose.

In December 2017, after 3 months of the CBE prescription, his mother increased the dose to 0.2 mL twice a day (4 mg CBD and 0.2 mg THC) as the family noted only mild improvements in anxiety symptoms. In August 2018, a medical cannabis follow-up was conducted. At 0.2 mL twice a day for almost 9 months, our patient’s family reported an improvement of 7 points for overall and social anxiety and irritability, and 6 points on aggressiveness on their respective VAS. Talkativeness improved by 4 points and focus by 2 points. In February 2020, another medical cannabis follow-up was conducted and positive effects were still evident at the same dose. When the mother was asked to complete the Children’s Sleep Habits Questionnaire (CSHQ) Abbreviated, she stated that he slept 7 hours and only had trouble falling asleep in his own bed as he resists going to bed. No side effects were reported (nausea/vomiting, diarrhea, headaches, euphoria, feeling high, anxiety, panic attacks, palpitations, somnolence during the day or drowsiness). Laboratory results remained normal and low ferritin was corrected. He began to initiate and reciprocate conversations with acquaintances he had previously been unable to speak to (for example, doctors, community members). He became more motivated and energetic, starting his own vegetarian diet and exercise programs, ultimately losing 6.4 kg after starting CBE for a calculated BMI of 21.33 kg/m 2 . He was able to start his first part-time job helping customers and interacting with them. He was instructed to fill out the self-administered Adult AQ which resulted in a normal score of 10 as shown in Table  1 . His mother stated he now also has a girlfriend. Recently, his mother started weaning him off CBE to go on a trip and noted an immediate change. He became more irritable and aggressive.

In discussion with their neurologist, the family decided to wean lamotrigine while remaining on CBE (0.2 mL twice a day – 4 mg CBD and 0.2 mg THC). Unfortunately, there was a recurrence of seizures and lamotrigine was titrated back to the full 200 mg twice a day dose.

Currently, our patient remains on the same medication as mentioned above, as well as low dose of CBE. He has maintained the positive effect on his behavioral symptoms, anxiety, sleep, and social deficits on CBE 1:20 ratio, 0.2 mL twice a day (4 mg CBD and 0.2 mg THC) and no side effects have been reported.

This case demonstrates the benefit of a lower than previously studied CBE dose for core social communicative and behavioral ASD symptoms, as well as improvements in co-occurring anxiety, sleep dysregulation, and weight, which led to substantial improvements in both our patient’s and his family’s quality of life and daily functioning. There was partial response at the initial dose of 0.1 mL twice a day (2 mg CBD and 0.1 mg THC) and a dramatic response at 0.2 mL twice a day (4 mg CBD and 0.2 mg THC). Seizures recurred when conventional anti-epileptic medication (lamotrigine) was weaned while on the CBE at the 0.1 mL twice a day dose (low doses), reiterating CBE at this dose did not have any significant anti-epileptic effect; lamotrigine has not been weaned while on the 0.2 mL twice a day (4 mg CBD and 0.2 mg THC) dose of CBE. Typically, significant higher CBD doses are needed for seizure control (> 20 mg/kg per day) [ 14 , 15 ].

The symptom improvement occurred within a 6-month period following the initiation of CBE treatment, during which time there were no new additions or significant alterations of/to any concurrent medications or therapies that could otherwise explain the improvements in symptomatology. It remains unclear whether the CBE directly modified the core ASD symptoms in some way, or whether the impact of CBE was secondary to its positive effects on comorbid conditions, namely anxiety and/or sleep dysregulation, which were producing or exacerbating underlying ASD behaviors. We must also consider there are limitations inherent in the method used to assess his clinical improvement, as the VAS and the AQ are not yet validated. These measures were chosen by default, as no scale is currently validated to assess clinical progress [ 3 ]. Seizures recurred at the initial 0.1 mL twice a day (2 mg CBD and 0.1 mg THC) dose of CBE. In addition to the fact that seizures were well controlled prior to starting CBE, the recurrence of seizures on the initial 0.1 mL twice a day dose of CBE, a dose at which symptoms were already starting to improve, suggests that improvements in ASD symptoms were not related to improvements in epilepsy control; the anti-seizure properties of CBD alone are unlikely to be the predominant mechanism responsible for the improvements in this patient’s ASD symptoms.

The ECS is a unique biological system that is present in the majority of body tissues. It plays an important role in cellular processes at the early stages of development [ 21 ]. The ECS is an essential regulatory system of the central nervous system that modulates both neurotransmission and synaptic plasticity. It is also involved in emotional and social functioning, and cognition [ 1 , 21 ]. There is evidence that the ECS is underdeveloped in ASD [ 1 , 22 ]. CBD may be treating core symptoms in ASD by interacting with the ECS to boost function in one way. CBD may increase the availability of the endogenous cannabinoids, anandamide (AEA), by directly inhibiting one of its degrading enzymes, that is, fatty amide acid hydrolase (FAAH) [ 1 , 23 , 24 ]. Wei et al. demonstrated that selective inhibition of FAAH in BTBR animals, increased AEA activity [ 25 ]. Further to this, a case–control study by Karhson et al . assessed AEA concentrations in ASD ( n  = 59) versus controls, and found lower AEA concentrations associated with ASD [ 26 ].

High-dose CBD has been studied for seizures and has been approved by the FDA (Epidiolex) for the treatment of intractable epilepsy [ 14 , 15 , 27 , 28 ], but there remains a lack of evidence for the use of phytocannabinoids in ASD [ 11 ]. Only a few low-powered studies address the clinical efficacy of cannabinoids for such symptoms, and there are no established recommendations for its use in ASD treatment [ 5 , 6 ]. The majority of published studies for ASD either involve synthetic cannabinoids [ 11 , 17 , 18 ] or synthetic enzyme-inhibitors [ 25 , 29 ]. Only a few studies offer evidence for the use of phytocannabinoids in ASD. An observational study by Bar-Lev Schleider et al. provided valuable information on safety and efficacy, but the study design was insufficient to draw strong conclusions on standard clinical care [ 19 ]. Clinicaltrials.gov lists an ongoing randomized trial comparing different phytocannabinoid extracts in the setting of behavioral symptoms, but results are not yet available [ 30 ]. Therefore, this case report is rare as it documents observed effects of CBE in ASD-related symptoms as opposed to other forms of cannabinoids (for example, nabilone, dronabinol, and nabiximols).

From a clinical perspective, the use of CBD-based products to treat neuropsychiatric symptoms must be done only after appropriate education and informed discussion with families, including consideration of risks and benefits of CBD compared to other available treatment options, and with vigilant monitoring.

Research into the role of cannabinoids in treating ASD symptoms and associated behaviors is in its infancy. Although there is an increasing amount of evidence providing biological plausibility for the use of CBD in treating ASD [ 1 , 5 , 25 , 26 , 31 ], further research is essential to better understand the effects of phytocannabinoids on neurobiological pathways and their impact on behavior and brain function. Rigorous, controlled clinical trials are needed to further establish safety, especially long-term safety, optimal dosing, and efficacy, including further delineation of the effect of CBE on core versus associated ASD symptoms. Until sufficient, supportive evidence is found, CBE remains an unproven alternative treatment and should not replace conventional evidence-based treatments for children with autism. However, the unexpected and significant benefits of CBE in this case report highlight the urgent need and potential benefits of continuing to pursue research in this area.

While there is a lack of strong evidence to support the use of CBE in ASD, this case report provides the first insight about lower than previously reported doses of phytocannabinoids in the form of CBE, which may benefit ASD-related behavioral and core social symptoms, as well as anxiety, sleep disturbances, and weight. We encourage scientists and clinicians to pioneer placebo-controlled studies to validate the clinical efficacy of very low doses of CBE in a larger cohort.

Availability of data and materials

The dataset generated and analyzed during this case report are available in Netcare (Alberta’s public Electronic Health Record used to store patient information).

Abbreviations

Autism spectrum disorder

Endocannabinoid system

Food and Drug Administration

Complementary and alternative medicine

Cannabidiol

Computed tomography

Child and Youth Mental Health

Fatty amide acid hydrolase

Delta-9-tetrahydrocannabinol

Cannabidiol-based extract

Interior Health Children’s Assessment Network

Magnetic resonance imaging

Autism Diagnostic Interview – Revised

Autism Diagnostic Observation Schedule 2

Alberta Children’s Hospital

Valproic acid

Body mass index

British Columbia

Visual analog scale

Children’s Sleep Habits Questionnaire

Autism Spectrum Quotient

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Ponton, J.A., Smyth, K., Soumbasis, E. et al. A pediatric patient with autism spectrum disorder and epilepsy using cannabinoid extracts as complementary therapy: a case report. J Med Case Reports 14 , 162 (2020). https://doi.org/10.1186/s13256-020-02478-7

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• Diseases & Conditions
• Autism spectrum disorder

Your child's doctor will look for signs of developmental delays at regular checkups. If your child shows any symptoms of autism spectrum disorder, you'll likely be referred to a specialist who treats children with autism spectrum disorder, such as a child psychiatrist or psychologist, pediatric neurologist, or developmental pediatrician, for an evaluation.

Because autism spectrum disorder varies widely in symptoms and severity, making a diagnosis may be difficult. There isn't a specific medical test to determine the disorder. Instead, a specialist may:

• Observe your child and ask how your child's social interactions, communication skills and behavior have developed and changed over time
• Give your child tests covering hearing, speech, language, developmental level, and social and behavioral issues
• Present structured social and communication interactions to your child and score the performance
• Use the criteria in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), published by the American Psychiatric Association
• Include other specialists in determining a diagnosis
• Recommend genetic testing to identify whether your child has a genetic disorder such as Rett syndrome or fragile X syndrome

No cure exists for autism spectrum disorder, and there is no one-size-fits-all treatment. The goal of treatment is to maximize your child's ability to function by reducing autism spectrum disorder symptoms and supporting development and learning. Early intervention during the preschool years can help your child learn critical social, communication, functional and behavioral skills.

The range of home-based and school-based treatments and interventions for autism spectrum disorder can be overwhelming, and your child's needs may change over time. Your health care provider can recommend options and help identify resources in your area.

If your child is diagnosed with autism spectrum disorder, talk to experts about creating a treatment strategy and build a team of professionals to meet your child's needs.

Treatment options may include:

• Behavior and communication therapies. Many programs address the range of social, language and behavioral difficulties associated with autism spectrum disorder. Some programs focus on reducing problem behaviors and teaching new skills. Other programs focus on teaching children how to act in social situations or communicate better with others. Applied behavior analysis (ABA) can help children learn new skills and generalize these skills to multiple situations through a reward-based motivation system.
• Educational therapies. Children with autism spectrum disorder often respond well to highly structured educational programs. Successful programs typically include a team of specialists and a variety of activities to improve social skills, communication and behavior. Preschool children who receive intensive, individualized behavioral interventions often show good progress.
• Family therapies. Parents and other family members can learn how to play and interact with their children in ways that promote social interaction skills, manage problem behaviors, and teach daily living skills and communication.
• Other therapies. Depending on your child's needs, speech therapy to improve communication skills, occupational therapy to teach activities of daily living, and physical therapy to improve movement and balance may be beneficial. A psychologist can recommend ways to address problem behavior.
• Medications. No medication can improve the core signs of autism spectrum disorder, but specific medications can help control symptoms. For example, certain medications may be prescribed if your child is hyperactive; antipsychotic drugs are sometimes used to treat severe behavioral problems; and antidepressants may be prescribed for anxiety. Keep all health care providers updated on any medications or supplements your child is taking. Some medications and supplements can interact, causing dangerous side effects.

Managing other medical and mental health conditions

In addition to autism spectrum disorder, children, teens and adults can also experience:

• Medical health issues. Children with autism spectrum disorder may also have medical issues, such as epilepsy, sleep disorders, limited food preferences or stomach problems. Ask your child's doctor how to best manage these conditions together.
• Problems with transition to adulthood. Teens and young adults with autism spectrum disorder may have difficulty understanding body changes. Also, social situations become increasingly complex in adolescence, and there may be less tolerance for individual differences. Behavior problems may be challenging during the teen years.
• Other mental health disorders. Teens and adults with autism spectrum disorder often experience other mental health disorders, such as anxiety and depression. Your doctor, mental health professional, and community advocacy and service organizations can offer help.

Planning for the future

Children with autism spectrum disorder typically continue to learn and compensate for problems throughout life, but most will continue to require some level of support. Planning for your child's future opportunities, such as employment, college, living situation, independence and the services required for support can make this process smoother.

More Information

• Cognitive behavioral therapy

Clinical trials

Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition.

Alternative medicine

Because autism spectrum disorder can't be cured, many parents seek alternative or complementary therapies, but these treatments have little or no research to show that they're effective. You could, unintentionally, reinforce negative behaviors. And some alternative treatments are potentially dangerous.

Talk with your child's doctor about the scientific evidence of any therapy that you're considering for your child.

Examples of complementary and alternative therapies that may offer some benefit when used in combination with evidence-based treatments include:

• Creative therapies. Some parents choose to supplement educational and medical intervention with art therapy or music therapy, which focuses on reducing a child's sensitivity to touch or sound. These therapies may offer some benefit when used along with other treatments.
• Sensory-based therapies. These therapies are based on the unproven theory that people with autism spectrum disorder have a sensory processing disorder that causes problems tolerating or processing sensory information, such as touch, balance and hearing. Therapists use brushes, squeeze toys, trampolines and other materials to stimulate these senses. Research has not shown these therapies to be effective, but it's possible they may offer some benefit when used along with other treatments.
• Massage. While massage may be relaxing, there isn't enough evidence to determine if it improves symptoms of autism spectrum disorder.
• Pet or horse therapy. Pets can provide companionship and recreation, but more research is needed to determine whether interaction with animals improves symptoms of autism spectrum disorder.

Some complementary and alternative therapies may not be harmful, but there's no evidence that they're helpful. Some may also include significant financial cost and be difficult to implement. Examples of these therapies include:

• Special diets. There's no evidence that special diets are an effective treatment for autism spectrum disorder. And for growing children, restrictive diets can lead to nutritional deficiencies. If you decide to pursue a restrictive diet, work with a registered dietitian to create an appropriate meal plan for your child.
• Vitamin supplements and probiotics. Although not harmful when used in normal amounts, there is no evidence they are beneficial for autism spectrum disorder symptoms, and supplements can be expensive. Talk to your doctor about vitamins and other supplements and the appropriate dosage for your child.
• Acupuncture. This therapy has been used with the goal of improving autism spectrum disorder symptoms, but the effectiveness of acupuncture is not supported by research.

Some complementary and alternative treatments do not have evidence that they are beneficial and they're potentially dangerous. Examples of complementary and alternative treatments that are not recommended for autism spectrum disorder include:

• Chelation therapy. This treatment is said to remove mercury and other heavy metals from the body, but there's no known link with autism spectrum disorder. Chelation therapy for autism spectrum disorder is not supported by research evidence and can be very dangerous. In some cases, children treated with chelation therapy have died.
• Hyperbaric oxygen treatments. Hyperbaric oxygen is a treatment that involves breathing oxygen inside a pressurized chamber. This treatment has not been shown to be effective in treating autism spectrum disorder symptoms and is not approved by the Food and Drug Administration (FDA) for this use.
• Intravenous immunoglobulin (IVIG) infusions. There is no evidence that using IVIG infusions improves autism spectrum disorder, and the FDA has not approved immunoglobulin products for this use.

Coping and support

Raising a child with autism spectrum disorder can be physically exhausting and emotionally draining. These suggestions may help:

• Find a team of trusted professionals. A team, coordinated by your doctor, may include social workers, teachers, therapists, and a case manager or service coordinator. These professionals can help identify and evaluate the resources in your area and explain financial services and state and federal programs for children and adults with disabilities.
• Keep records of visits with service providers. Your child may have visits, evaluations and meetings with many people involved in his or her care. Keep an organized file of these meetings and reports to help you decide about treatment options and monitor progress.
• Learn about the disorder. There are many myths and misconceptions about autism spectrum disorder. Learning the truth can help you better understand your child and his or her attempts to communicate.
• Take time for yourself and other family members. Caring for a child with autism spectrum disorder can put stress on your personal relationships and your family. To avoid burnout, take time out to relax, exercise or enjoy your favorite activities. Try to schedule one-on-one time with your other children and plan date nights with your spouse or partner — even if it's just watching a movie together after the children go to bed.
• Seek out other families of children with autism spectrum disorder. Other families struggling with the challenges of autism spectrum disorder may have useful advice. Some communities have support groups for parents and siblings of children with the disorder.
• Ask your doctor about new technologies and therapies. Researchers continue to explore new approaches to help children with autism spectrum disorder. See the Centers for Disease Control and Prevention website on autism spectrum disorders for helpful materials and links to resources.

Preparing for your appointment

Your child's health care provider will look for developmental problems at regular checkups. Mention any concerns you have during your appointment. If your child shows any signs of autism spectrum disorder, you'll likely be referred to a specialist who treats children with the disorder for an evaluation.

Bring a family member or friend with you to the appointment, if possible, to help you remember information and for emotional support.

Here's some information to help you prepare for your appointment.

What you can do

Before your child's appointment, make a list of:

• Any medications, including vitamins, herbs and over-the-counter medicines that your child is taking, and their dosages.
• Any concerns you have about your child's development and behavior.
• When your child began talking and reaching developmental milestones. If your child has siblings, also share information about when they reached their milestones.
• A description of how your child plays and interacts with other children, siblings and parents.
• Questions to ask your child's doctor to make the most of your time.

In addition, it may be helpful to bring:

• Notes of any observations from other adults and caregivers, such as babysitters, relatives and teachers. If your child has been evaluated by other health care professionals or an early intervention or school program, bring this assessment.
• A record of developmental milestones for your child, such as a baby book or baby calendar, if you have one.
• A video of your child's unusual behaviors or movements, if you have one.

Questions to ask your child's doctor may include:

• Why do you think my child does (or doesn't) have autism spectrum disorder?
• Is there a way to confirm the diagnosis?
• If my child does have autism spectrum disorder, is there a way to tell how severe it is?
• What changes can I expect to see in my child over time?
• What kind of special therapies or care do children with autism spectrum disorder need?
• How much and what kinds of regular medical care will my child need?
• What kind of support is available to families of children with autism spectrum disorder?
• How can I learn more about autism spectrum disorder?

Don't hesitate to ask other questions during your appointment.

What to expect from your child's doctor

Your child's doctor is likely to ask you a number of questions. Be ready to answer them to reserve time to go over any points you want to focus on. Your doctor may ask:

• What specific behaviors prompted your visit today?
• When did you first notice these signs in your child? Have others noticed signs?
• Have these behaviors been continuous or occasional?
• Does your child have any other symptoms that might seem unrelated to autism spectrum disorder, such as stomach problems?
• Does anything seem to improve your child's symptoms?
• What, if anything, appears to worsen symptoms?
• When did your child first crawl? Walk? Say his or her first word?
• What are some of your child's favorite activities?
• How does your child interact with you, siblings and other children? Does your child show interest in others, make eye contact, smile or want to play with others?
• Does your child have a family history of autism spectrum disorder, language delay, Rett syndrome, obsessive-compulsive disorder, or anxiety or other mood disorders?
• What is your child's education plan? What services does he or she receive through school?
• Autism spectrum disorder (ASD). Centers for Disease Control and Prevention. https://www.cdc.gov/ncbddd/autism/facts.html. Accessed April 4, 2017.
• Uno Y, et al. Early exposure to the combined measles-mumps-rubella vaccine and thimerosal-containing vaccines and risk of autism spectrum disorder. Vaccine. 2015;33:2511.
• Taylor LE, et al. Vaccines are not associated with autism: An evidence-based meta-analysis of case-control and cohort studies. Vaccine. 2014;32:3623.
• Weissman L, et al. Autism spectrum disorder in children and adolescents: Overview of management. https://www.uptodate.com/home. Accessed April 4, 2017.
• Autism spectrum disorder. In: Diagnostic and Statistical Manual of Mental Disorders DSM-5. 5th ed. Arlington, Va.: American Psychiatric Association; 2013. http://dsm.psychiatryonline.org. Accessed April 4, 2017.
• Weissman L, et al. Autism spectrum disorder in children and adolescents: Complementary and alternative therapies. https://www.uptodate.com/home. Accessed April 4, 2017.
• Augustyn M. Autism spectrum disorder: Terminology, epidemiology, and pathogenesis. https://www.uptodate.com/home. Accessed April 4, 2017.
• Bridgemohan C. Autism spectrum disorder: Surveillance and screening in primary care. https://www.uptodate.com/home. Accessed April 4, 2017.
• Levy SE, et al. Complementary and alternative medicine treatments for children with autism spectrum disorder. Child and Adolescent Psychiatric Clinics of North America. 2015;24:117.
• Brondino N, et al. Complementary and alternative therapies for autism spectrum disorder. Evidence-Based Complementary and Alternative Medicine. http://dx.doi.org/10.1155/2015/258589. Accessed April 4, 2017.
• Volkmar F, et al. Practice parameter for the assessment and treatment of children and adolescents with autism spectrum disorder. Journal of the American Academy of Child and Adolescent Psychiatry. 2014;53:237.
• Autism spectrum disorder (ASD). Eunice Kennedy Shriver National Institute of Child Health and Human Development. https://www.nichd.nih.gov/health/topics/autism/Pages/default.aspx. Accessed April 4, 2017.
• American Academy of Pediatrics policy statement: Sensory integration therapies for children with developmental and behavioral disorders. Pediatrics. 2012;129:1186.
• James S, et al. Chelation for autism spectrum disorder (ASD). Cochrane Database of Systematic Reviews. http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010766.pub2/abstract;jsessionid=9467860F2028507DFC5B69615F622F78.f04t02. Accessed April 4, 2017.
• Van Schalkwyk GI, et al. Autism spectrum disorders: Challenges and opportunities for transition to adulthood. Child and Adolescent Psychiatric Clinics of North America. 2017;26:329.
• Autism. Natural Medicines. https://naturalmedicines.therapeuticresearch.com. Accessed April 4, 2017.
• Autism: Beware of potentially dangerous therapies and products. U.S. Food and Drug Administration. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm394757.htm?source=govdelivery&utm_medium=email&utm_source=govdelivery. Accessed May 19, 2017.
• Drutz JE. Autism spectrum disorder and chronic disease: No evidence for vaccines or thimerosal as a contributing factor. https://www.uptodate.com/home. Accessed May 19, 2017.
• Weissman L, et al. Autism spectrum disorder in children and adolescents: Behavioral and educational interventions. https://www.uptodate.com/home. Accessed May 19, 2017.
• Huebner AR (expert opinion). Mayo Clinic, Rochester, Minn. June 7, 2017.
• Autism spectrum disorder and digestive symptoms

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Case Studies for the Treatment of Autism Spectrum Disorder

Ideal for preparing SLPs and other clinicians to make sound decisions, this casebook gives readers in-depth, real world demonstrations of today’s evidence-based interventions for children with autism spectrum disorder (ASD). Developed as a companion to the Treatment of Autism Spectrum Disorder textbook—but equally useful as a standalone casebook—this resource offers 14 realistic case studies that walk readers through common clinical challenges and help them hone their planning and problem-solving skills.

• Product Details
• Table of Contents
• Contributors
• A complete profile of the child’s strengths and needs , with a special focus on communication and social skills
• An overview of assessment practices that inform communication treatment planning
• A discussion of the clinical problem-solving processes used to identify treatment goals and strategies
• An intervention plan used to achieve the child’s goals, with details on implementation and modifications
• A report on the child’s outcomes
• A set of learning activities to help readers apply their knowledge

A one-of-a-kind practical resource developed by clinical experts, this casebook will help both current and future professionals understand today’s widely used autism interventions—and prepare to implement them effectively in their own practice.

GET THE BUNDLE: Buy this casebook as a bundle with its companion textbook, Treatment of Autism Spectrum Disorder, Second Edition . The new edition of this essential text gives SLPs the foundation they need to evaluate, select, and implement 14 of today’s widely used interventions.

• SLPPD 623 Communication Disorders in Autism
• SLHS 519 Language and Communicationin Austism Spectrum Disorders
• CSD 4900 Autism Spectrum Disorders
• 6230 Assessment & Intervention for Autism

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Autism Breakthrough: New Treatment Significantly Improves Social Skills and Brain Function

By Tel-Aviv University November 29, 2022

The researchers anticipate that the study’s success will have positive implications for clinical treatment.

The treatment caused neurological changes, including a decrease in inflammation and an increase in functionality, according to the researchers.

A recent Tel Aviv University study found that pressure chamber therapy greatly improved social skills and the condition of the autistic brain. The research was carried out on autism animal models. The researchers discovered changes in the brain, including a decrease in neuroinflammation, which has been linked to autism. Furthermore, the social functioning of the animal models treated in the pressure chamber improved significantly. The success of the research has significant implications for the applicability and understanding of pressure chamber therapy as a treatment for autism.

Inbar Fischer, a Ph.D. student in Dr. Boaz Barak’s lab at Tel Aviv University’s Sagol School of Neuroscience and School of Psychological Sciences, led the team that made the discovery. The findings were recently published in the International Journal of Molecular Sciences .

According to Fischer and Barak, hyperbaric medicine is a kind of treatment in which patients are treated in special chambers where the atmospheric pressure is greater than the pressure we experience at sea level, and they are also given 100% oxygen to breathe. Hyperbaric medicine is already being used to treat a wide range of medical conditions and is considered to be safe. Scientific evidence has accumulated in recent years that certain protocols of hyperbaric treatments boost the supply of blood and oxygen to the brain, thereby increasing brain function.

Dr. Barak: “The medical causes of autism are numerous and varied, and ultimately create the diverse autistic spectrum with which we are familiar. About 20 percent of autistic cases today are explained by genetic causes, that is, those involving genetic defects, but not necessarily ones that are inherited from the parents. Despite the variety of sources of autism, the entire spectrum of behavioral problems associated with it are still included under the single broad heading of ‘autism,’ and the treatments and medications offered do not necessarily correspond directly to the reason why the autism developed.”

In the preliminary phase of the study, a girl carrying the mutation in the SHANK3 gene, which is known to lead to autism, was treated by Prof. Shai Efrati. He is director of the Sagol Center for Hyperbaric Medicine at the Shamir “Assaf Harofeh” Medical Center, a faculty member at the Sagol School of Neuroscience, and a partner in the study. Upon completing a series of treatments in the pressure chamber, it was evident that the girl’s social abilities and brain function had improved considerably.

In the next stage, and in order to comprehend the success of the treatment more deeply, the team of researchers at Dr. Barak’s laboratory sought to understand what being in a pressurized chamber does to the brain. To this end, the researchers used adult animal models carrying the same genetic mutation in the SHANK3 gene as that carried by the girl who had been treated. The experiment comprised a protocol of 40 one-hour treatments in a pressure chamber, which lasted several weeks.

Dr. Barak: “We discovered that treatment in the oxygen-enriched pressure chamber reduces inflammation in the brain and leads to an increase in the expression of substances responsible for improving blood and oxygen supply to the brain, and therefore brain function. In addition, we saw a decrease in the number of microglial cells, immune system cells that indicate inflammation, which is associated with autism.

“Beyond the neurological findings we discovered, what interested us more than anything was to see whether these improvements in the brain also led to an improvement in social behavior, which is known to be impaired in autistic individuals,” adds Dr. Barak.

“To our surprise, the findings showed a significant improvement in the social behavior of the animal models of autism that underwent treatment in the pressure chamber compared to those in the control group, who were exposed to air at normal pressure, and without oxygen enrichment. The animal models that underwent treatment displayed increased social interest, preferring to spend more time in the company of new animals to which they were exposed in comparison to the animal models from the control group.”

Inbar Fischer concludes: “The mutation in the animal models is identical to the mutation that exists in humans. Therefore, our research is likely to have clinical implications for improving the pathological condition of autism resulting from this genetic mutation, and likely also of autism stemming from other causes. Because the pressure chamber treatment is non-intrusive and has been found to be safe, our findings are encouraging and demonstrate that this treatment may improve these behavioral and neurological aspects in humans as well, in addition to offering a scientific explanation of how they occur in the brain.”

Reference: “Hyperbaric Oxygen Therapy Alleviates Social Behavior Dysfunction and Neuroinflammation in a Mouse Model for Autism Spectrum Disorders” by Inbar Fischer, Sophie Shohat, Gilad Levy, Ela Bar, Sari Schokoroy Trangle, Shai Efrati and Boaz Barak, 21 September 2022, International Journal of Molecular Sciences . DOI: 10.3390/ijms231911077

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144 comments on "autism breakthrough: new treatment significantly improves social skills and brain function".

So how do they know that the effect is caused by the pressure and not by the oxygen?

A very promising news.

if this was true then i’d expect to see this news everywhere i look, not just on this one site truth is, there isn’t enough research on this right now to truly say if this can help manage autism lets just treat autistic people like normal, aye?

do your own reading if you like: https://www.nice.org.uk/donotdo/do-not-use-hyperbaric-oxygen-therapy-to-manage-autism-in-any-context-in-children-and-young-people https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5471082/ https://asatonline.org/for-parents/becoming-a-savvy-consumer/hyperbaric-oxygen-therapy/

i feel like if this was legit we’d be seeing news about this everywhere (which i’m not seeing) doing my own research concludes that this “treatment” is shaky at best, and hasn’t been given the proper scientific investigation it may or may not deserve

i don’t think i’m allowed to share links here, so just search up “hyperbaric chamber autism” and do your own research for now, let’s just not try to alienate autistic people aye?

Begs the question…. how long does the improved behavioral and neurological improvements last–days, weeks, months, years? Are additional hyperbaric treatments needed to maintain these improvements?

Maybe i don’t want to be social. Maybe my autism doesn’t need to be “fixed”.

If you’re happy as you are, that’s genuinely awesome, you don’t need to try it. But there are lots of people who would love to have it better managed than what is currently offered.

What you want might not be what the next person wants, though.

Allow me to clarify what Danielle might have been getting at. The characteristics of autism are part of us. Sure, learning life skills through OT, doing speech therapy, etc can be super useful and good for people with ASD to have a better quality of life. But neurotypicals trying to “fix” their autism because their autistic-ness doesnt fit in with society. The problem here isnt that people with autism are perfectly happy with their quality of life. Being autistic in this society sucks. Its horrible. But what a lot of autistics want is for society to change- being more inclusive, accepting, and accessable- not constantly hear how neurotypical society thinks they can and need to change us.

Exactly! Society disables us…we don’t need treatments or cures, just understanding.

You don’t need those things. But some autistic people do.

Please make room for *their* lived experience of autism, as you would like other people to make room for yours.

It’s a disability and many of us would like to treat or cure certain aspects to make our day to day life easier.

Well said! Articles like this give me rage.

Maybe the autistic people in the study were more regulated because the sensory environment of the hyperbaric oxygen tanks was ideal for them? And maybe there is nothing wrong with autistic people’s socialization, maybe it’s just different.

So my question is what the expectations are and how will preparations be made in the outcome of humans treated with this method in correlation to the absence of consciousness in a person. How will the transition be for the peraon treated. Would it be like the person experiencing birth? What are the difficulties of this?

This is fascinating to see used as a treatment. The implications and subsequent results would constitute being better classified as a cure. As for the people with negative responses to this, this is a new study, not going to see a lot of news, still in lab trials, for the one that doesn’t want autism fixed, ignorance is bliss, but please keep that ignorance to yourself. My specific form of autism is quite painful. Increasing my brain function would be fantastic. If you find that insulting, that is awesome. What are you doing looking at cures and treatments for something you are comfortable with? Wouldn’t you find something positive to occupy yourself with?

This research presents autism as a genetic weakness that needs to be cured which it is not it is neurodiversity which in many cases is proven to be an advantage Elon musk, Isaac Newton, Albert Einstein and many more had autism and they flourished. We need to help the disadvantages that autism brings and nurture the extraordinary things it does not try to eliminate it all together. This project is a pure example of fascism the belief that one group of people is superior to another. I feel sorry for the people and animals that have and will be in this experiment.

Anything that helps me achieve my goals is good for me. I want to more easily relate to others. I want a family. I don’t want people to feel like they were born with a disease, but I’d like options on how my own brain functions. It’s possible that given the nature of excess throughout history people will take this too far. However we need more options now and we can try to be better to reach other as we go on.

I’m going to need to see this replicated on more than a human sample size of one. When you treat one single person with something you will not be able to fully generalize their result/success rate to a population as diverse as the autism one, and the scientists even acknowledge it themselves, saying autistic behavior comes from so many different sources but are grouped together under one diagnostic label.

Why try to fix us? We are humans with a different ways of understanding and as far as I know you’ll never find an autistic tyrant or something worse We as people have a right as everyone yet it’s a problem to be fixed and if it’s just a model then I guess soon you’ll be wanting people so you’ll as parents for volunteers yeah right I’m dyslexic/autistic person who has finally accepted myself for who I am I’m a person not a problem to be fixed.

Wow I have seen the different reactions from people who are autistic and wonder if there is a need for further research and diversity and maybe direction as to the source of this (difference) in structure and function of the brain that leads to the classification of autism. If there is a seemingly a discovery of a treatment or protocol that will make for a better life for such people, why shoot it down.

Hey there sheeple! Just FYI in 99% of the times Autism is a vaccine injury induced by aluminum breaching the blood brain barrier using Polysorbate 80. Also, there are protocols to detoxify the brain and effectively cure Autism using heavy metals chelators such as Chlorine Dioxide . You can find more info all over Telegram

This is idiotic. Take your BS elsewhere.

Go get a booster it’s good for your sheeple heart and will rid us of your carbon

Useless conspiracy theorist idiots wouldn’t understand science if it slapped them.

Absolute crap… I was born autistic, as was every other autistic person. Autism existed before vaccines and is an evolutionary development.

$CIENCE! IT’S ALL FAKE BS shilling for pharma companies

Why is this drivel even being published? The premise upon which this nonsense is based is flawed as it is treating being autistic as something that needs to be “cured”. The people conducting the study are clearly not up to date in their understanding of what it means to be autistic as they seem to think that only 20% of autistic people’s neurology is due to genetic mutation and seems to dismiss any idea that autistic parents have autistic kids. That would,of course require them to admit that autistic people are full members of society who can have families, jobs etc.

I wonder where the funding for this nonsense came from.

You are defensive. No one is forced to do anything. Simple as hyperbaric oxygen is, it definitely has positive short term effects on cognition. Now that makes this interesting g to those open to learn. All autism is not the point… maybe some cases benefit in ways some autistic individuals will find beneficial. You don’t get to decide that for the universe. You should just step out if this thread if that’s your oersodctive.

Wow…it is quite incredible to observe, as a neurodivergent person within the spectrum, how certain individuals have such immature reactions due to a biased position. No one said that the persons under the spectrum constitute a problem, because they aren’t, indeed, we are different and wonderful in so many ways. But it is a SPECTRUM and there are persons within its range, that suffer intensely and actually would benefit from certain forms of therapy. If the quality of life ( which was the actual PROBLEM that was addressed ) can be increased for certain individuals that do face different problems and difficulties and their life, that’s great news. For your own good, learn to think outside yourself, because from what I see there can exist the tendency to negate somebody else’s reality and struggles when you are generalising.

Well said Vanilla Cat

Thank you for saying that so well.

Freddy, easy for you to say until it affects your own child and you have to help them function daily. Not all autistic people get along just fine without treatment and support and to assert that they can is privileged and ignorant.

I have 2 children on the spectrum and one full blown moderate to severe ASPERGERS. I have been a Critica Care , Clinical Care Specialty Nurse for 30 years, we came before Nurse Practioner’s , yes I am old.

I am familiar with hyperbaric therapy, obviously for lung conditions.

As one who has done much research on my Children’s Conditions, they were all adopted, 2 from Ukraine, 1 from China and my most complex child was a domestic adoption, we adopted Danny at 7 days old, he is 19. He has a rare Genetic Disorder, Partial Trisomy 3Q29 and Epilepsy, and a Chiari 1 Brain Malformation, and Cortical Visual Impairment with depth perception problems. He has severe global and cognitive delays and Autistic Spectrum, and my 24 year old from Ukraine Fetal Alcohol Disorder, Lily 13 year old daughter is the Asperger’s.

Yes super smart but cannot get a bath and get dressed in the morning without me.

So just because this has not been researched on AUTISM very well I’m this country, does not mean we have to sit around and say “ well I guess I wait 20 years and then find out it could have helped my kids tremendously, no we rally as advocates for our loved ones and say, to Teaching Learning Hospitals, John’s Hopkins University Hospital, Jefferson University Hospital, University of Penn Hospital and petition some neurological, Autism Specialist, neuropsychology , Autism Psychiatrist who treat the very hard cases of ADHD/Asperger’s.

If this study gets more oxygenated blood to the brain, which let’s face it any medical and lay person knows that is a good thing, and if the pressure aspect is studied more in detail, this could be a breakthrough!!

I could have children that can actually feel emotions and can think about other people before their own needs. Autism is just not about being more social, it is a neurodevelopmental disorder just as ADHD.

All the sensory, odd behaviors, ticks, and with life skills and social skills if their is something as simple as pressure and oxygen that can even help these kids/Adults think better and feel better and understand themselves better, we should definitely push for more research.

Most parents and family of severely affected Autistic loved ones will understand this, High Functioning Autism Adults or teens who can function in the real world obviously, I am not including them, but like my A+ child who cannot get dressed or get on the run and she is 14 in 3 months, we will take all the help we can get.

If you do not live 24/7 with Autistic, several children, you will not understand a word I am saying, I live it, breath it, have gone to Doctors for decades, and if my kids could stop picking her head, Tick, my son could stop slapping his tongue and my oldest one paces and talks to himself, I really am going to advocate for this.

I have been in special needs, Disabled child Medicaid, IEP’s, Social Security fighting my butt off for years for my kids. So the question is where are the hyperbaric chambers located, we start their first.

Just a word from a beyond experienced SN Mom and a seasoned Specialist in Critical Care, I use ICP drains, I k ow what brains pressures can do.

Let’s put this together and it either does or does not work, what’s the worst that can happen your child remains absolutely the same, well you already have that down.

The “do your own research” BS has to STOP! It’s embarrassing. You can read what’s available but you ARE NOT doing “your own research”! Ask questions, read, inquire, but that is NOT research.

Do you think that a two year old would be able to deal with this treatment? This toddler can’t stand noise.

Hospitals use a 95%oxygen/5%carbon dioxide gas mixture on their coma patients. Would using that gas mixture, instead of the 100% oxygen in this hyperbaric treatment, make it even more effective?

How long will it take. My grandson would get anxious in a confined space for too long. Is it safe for someone to be in the chamber with them like a diving bell of something?

It’s garbage. It’s another scitech fairytale.

As a member of the autistic community articles like this are just plain offensive.

Your grandson is not defective, he’s not broken, he doesn’t need fixing. I know it can be challenging but give him the right stimulus and he’ll show you how awesome he can be.

@Andy: You don’t get to speak for everyone with Autism, or those that live with and/or help them. It’s not the case of treating all Autism as a problem, so that’s a false premise to begin with; sure some people may view it that way, but not all (and I doubt most) do.

As most that have experience with it know – It is a wide-spectrum: some can function just fine in society (with or without A-typical behaviour) and occasionally with advantageous developments in areas; these people are likely to be, and feel just fine about themselves and their role in society. They are more akin to the healthy autist that’s just a bit different (neurodivergent), but is otherwise happy/healthy/thriving; certainly not a problem to be fixed, but they are also not the typical case either.

Again, not all autists are the same; some thrive, some just need a bit of help, but some are genuinely unhappy with themselves and their condition and would like help – you don’t get to deny that reality for them.

On the other side of things; some can be severely inhibited (not just in wider society, but in the day-to-day tasks required to live, let alone thrive). What about the child that wants to give/have a hug, to have that closeness, but can’t stand the feeling on their skin and gets frustrated at themselves for it (sometimes to the point of self-harm)? Or the child that’s trying desperately to process language and communicate well enough so that those not in her immediate family can also understand her?

I’m sure it’s outrageously expensive.

I think this study sounds fascinating and I can totally see it working. I would love to know where this treatment will be offered. I think its definately worth a try.

Makes sense to me, an HFA. I always felt so much better after scuba diving and hyperbaric tanks recreate the pressures experienced when scuba diving.

Hyperbaric oxygen therapy provides a higher concentration of oxygen delivered in a chamber or tube containing higher than sea level atmospheric pressure. Case series and randomized controlled trials show no evidence to support the benefit of HBOT for children with ASD. Only 1 randomized controlled trial reported effectiveness of this treatment, and those results have yet to be repeated.

I tried this for my son on 2011. He was 7 years old at the time. I went with him in the chamber and laid down for about approx 2.5 hours each day. It was horrible being confined in a capsule like chamber. No effect. Spent thousands of money.

I’m okay the way I am. I’ve lived a long and sometimes difficult life caused by “normal” people who wanted to change me, punish me, fix me, and otherwise make me well aware that I am undeserving of the benefits and respect of the mainstream. This is more of the same bullying, and these scientists can go to Hell.

Very interesting lies, unaware people who don’t understand or experience sh*t would believe, but meditation and a little weed are the only things you need to fix THE TRAUMA DISORDERS AUTISM, AND ADHD. B**** *** **** hiding that most important fact from everyone. You baby was traumatized at some point at birth during birth,that’s autism and adhd

The connection between inflammation in the brain and autism is a big deal.

It would be great if this process could be created for individual use at home somehow. I also wonder about long term treatment or maintenance.

Zac Brace, professorC, etc al.: IF autism is indeed the result of inflammation of the brain, then this is not simply an example of “neurodiversity” but of an abnormal physiological condition. For every Elon Musk, Albert Einstein or Isaac Newton in history, there are thousands (perhaps millions) of autistic souls suffering throughout their lives and failing to optimize their potential. The significant disabilities of an autism spectrum disorder for many individuals warrants continued research for viable treatments. If you, as an autistic, have a satisfying rewarding, & independent life, good for you but don’t make the mistake of believing your autism parallels that of all others. My guess is your autism is not very significant, which would make you (yes) “neurodiverse”, not disabled.

Completely agree with your statement. It’s unbelievable that some would think that just because something works for them, that everyone else should be OK too. Ridiculous, we need advancements in autistic treatment now. My niece is suffering along with her sister who doesn’t understand why her autistic sister won’t play with her. It’s sad for both children.

I see people are still trying to FIX “the Autism problem”…

It’s only neurotypicals who experience anything other than what they perceive as normal as a problem that needs fixing.

Please do some research on what autism does to a parent that has a 4 year old that is non verbal, violent to self and others, hits. Screams and is completely unable to socialize in almost any type of surroundings. Many only sleep 2 or 3 hours a night, won’t eat and refuses potty training. Then you can decide that this is not good news. Until then your negative comments are very unhelpful and you come off as unfeeling towards the suffering of thousands of kids and their parents.You ATA

Id like to know more. What exsactly does the improved brain function help with. Only social issues? What about theself harm part? Would more oxygen and pressure help with the biting himself or smashing his head in the walls? Is this only for higher functioning autstics or can it help the more severe people too. I dont care about a cure so much as I would love to see my child enjoy life more and stop hurting himself as much. I love seeing more research on autism.

Jess, you don’t get to answer for everyone on the spectrum. Maybe higher functioning people will choose not to make any changes to themselves and that should totally be supported. But some on the spectrum cannot talk, function, ever hold a job, are violent to themselves and/or others. They deserve a chance to live a better life. What happens when my husband and I die? Who will care for my son so that he can be happy and not destructive? I have seen enough abuse of seniors and disabled to know he won’t stand a chance.

No offense, but some of us have been doing this for years for our kids with autism. It’s definitely not new.

I’m not quite sure how to address this article from this so called online magazine I have to stand thoroughly disgusted there’s nothing to fix I’m fine maybe it’s everyone else and maybe we’re just fine the way we are you can just sit in your hyperbolic chamber and eat Doritos and watch TV and we’ll do important things thank you

And yet again switch posting absolute garbage. I’ve seen more accurate reporting on Fox News.

I mean for a start autism is a genetic condition, usually inherited from parents even if they don’t present with autistic traits. Our brains function just fine, quite often better than NT peers, we just tend to be a bit more focused.

If you think autistic people are defective take every mechanical, electronic or other modern gadget out of your house because I can guarantee they were either designed, engineered, coded or otherwise created by people who are probably on the spectrum.

Articles like this are on the same level as Trump suggesting intravenous UV and Klorox.

Autistic people aren’t a defective kind of neurotypical people, we are whole people in our own right, we just have a different neurotype. Before nts say I’m ‘not like their autistic child’, just know that I’m regularly non verbal, unfit to work, and at times I often self harm and sui*. I’m also able to travel alone, I’ve a great network of friends, and go to clubs, pubs, gigs, and write poetry – its not black and white. What causes autistic people is sex. Not brain injury. Animals simply can’t be autistic, at least not in the way humans are, as they have different brains, and behaviours. It’s ableist to imply otherwise and this is hack science taking advantage of vulnerable autistic people and their hopeful parents and care givers.

Not all people with autism are high functioning. Many have significant behaviors and would benefit. My son did thus when he was young and it helped. But some of the positives fade. I think you need to do treatment long term like medication.

I have autism L2 and Fibromyalgia,It has been adviced that the same treat may help relieve pain of fibro.

Gods forbid another Albert Einstein, Michelangelo, Charles Darwin, Emily Dickinson, Bill Gates, Isaac Newton, Nikola Tesla, Vincent Van Gogh, Steven Spielberg, Jerry Seinfeld, Benjamin Franklin, Beethoven, Mozart, or Jane Austen use the brains they were born with to create groundbreaking art, science, literature, music, comedy, or anything else. Far more important to make them conform to neurotypical standards of social acceptability, amirite?

Oh, and if this so-called ‘treatment’ makes Autistic kids more neurotypical, then I guess we can expect them to become ruthless social climbers who are better liars, more dispassionate about their interests, more underhanded and conniving, and more willing to accept obsolete social rules without questioning them. But at least they’ll smile and make eye contact!

You see it from the social aspect alone. As a father of a 12 years old who can not use even the potty, has no speech, keep inflicting injuries on himself can’t sleep without tranquilizer most of the time not even aware of his our existence,you will realize that it is not just about socializing and eye contact. It is about self help. You may be on the mild end but I tell you a lot more are on the severe end and needed anything that gives a glimpse of hope.

Treat inflammation thru diet.

Autism is a very generic and diverse classification. I am certainly no expert, but I have seen totally nonfunctional autism and I have seen those who are capable of self-regulating function. It is very important that we help those who are in need of a basic quality of life.

I remember seeing a research presentation for hyperbaric oxygen chamber at a biomedical conference back in 2005. It sounded promising for certain case studies, but did not offer generalized results. What is new here?

Many with autism have texture phobias, balance issues and sometimes a little ADD, ADHD, some will spin, focus too much or too little on tasks at hand, some can be more sensitive to change in environment and like to take things apart or line em up rather than put them together. The pressure room can help regulate some of that because it can give them more balance and forthcoming control over movement and therefore à less interrupted thought process, not just deflaming the brain.. great idea.

Very interesting. Don’t see any harm in giving this option to those who are on the autism spectrum, and are interested and find this method may be useful to them. I find conversation much more interesting and intellectually stimulating when talking to friends who may be on the spectrum. There may be huge positives and some negatives (like all people) as we are all different. So with that being said it’s wonderful for scientists to study everything. To ask questions. To discover. Humans are fasting, so are our brains. Let’s be supportive. What one may see as minuscule and lacking in importance could change another life for the better!

So, if we decrease systemic inflammation, would that be another avenue?

I think it’s great news to be moving in the direction of either a cure or helping with the symptoms that affect many autistic children. Where would one find more information or how are clinical studies going to be done soon? Is I let available to everyone?

Stop trying to cure different. Your eugenics is showing. Different is not bad. Rather than trying to cure our existence why not try accepting us with understanding. Your pity looks like a tombstone.

I doubt very much the same treatment can possibly cure a spectrum of symptoms of varying degree, not necessarily interrelated and which may stem from environmental factors. Are we capable of changing a person’s character; the way they think; their likes; dislikes; their empathy, and whether others value their company? Of course not!

So autism could be symptom of neuro- inflammation?

It is very discouraging to see the high functioning autistic people on here be so negative about autism treatments! Not every autistic person has a choice if they want to be fixed or not. My son whom is 14 and can’t speak and still isn’t completely potty trained with major social deficits could certainly benefit from any breakthrough or treatments offered up. So many other severely autistic children and adults in the world that deserve to be free from the frustration and anxiety of extreme sensory overload and inability to communicate.To all of the higher functioning autistic I say this….you poor tortured souls that want to bask in your autism…go for it! But for the sake of the lower functioning or severely affected autistics that need help; be freaking respectful and mindful of what you say! (In honor of my son)

There is no such thing as “high functioning autistic people”… We are all just Autistic and present differently.

We don’t need treatments or cures. We are a different neurotype… We don’t have a disease! 🙄

Stephanie Brown you read my mind!! My grandson is severely autistic… he’s almost 6, doesn’t speak & isn’t potty trained. The difference between high functioning autism & the severely autistic is so profound they might as well be to different diagnoses. High functioning autistic individuals can speak for themselves, the severely autistic need their family to speak for them. I for one think this research is promising & just because it’s brand new & not all over the media doesn’t mean it’s false. For goodness sake it takes YEARS for changes to trickle down & be put into practice in the medical field. I’m hopeful to hear studies like this are happening & hopeful there will be something in the future that can help my grandson. I know there’s no such thing as “fixing” him but something that could help his enormous anxiety, confusion & anger. Something that’ll help him feel comfortable in his own body & this world.

“High functioning” autism is not a thing. Autism is Autism, and some Autistic people present differently. Stop using outdated labels.

How do I get some for my very hard to diagnose problem with hydrocephalus to take care of my adult dependent with Autism? He says he isn’t going in there. I think I need to at least try?

How long do the effects last outside the pressure chamber? Would one need to wear a pressurized diving helmet with a 100% oxygen feed to ‘cure’ one’s autism?

I fully agree with you Zak Brace.

Autism in the severest form is what this is about not functioning autistics. It bothers me that high ASD people would even comment in here the way they have. Live with a non verbal person and meltdowns then understand we need this kind of research. But I think vitamin e works just as well with relieving swelling in brain. Please research this

This supports the findings of the first “autistic researcher,” Temple Grandin, who invented a similar idea based on pressure, she called the Squeeze Machine.(See the movie made by HBO “Temple Grandin.”)

It also mentions the immune system relation to autism that was named in 2003 to associate autism with one of the 5 immune system disorders, called Common Variable Immune System Disorder, – which I was born with in 1949, and later assessed as caused by DDT poisoning of my mother when she was pregnant. (There was a LOT of crop dusting in the rural S. TX town we lived in.)

I am so happy to hear of this development and especially for my grandson who has autism and lives in Israel. And yes. I too would prefer people were treated in a real, loving expression toward each other and there more value in that enough that we had “application” training available.

I think the article refers to capacity. As in autistic people we’ll have a higher capacity for being social. I don’t think it means that they have to be social.

How do I get hepl

How can you test an animal for autism. That ridiculous. An animal can’t talk or anything. You need to test on adult who want to be tested. Testing animals is NOTHING like on a human being it’s common sense. If there were more help out there for autism more educational HELP. Then maybe they will learn how to deal with this world because this world is having a hard time dealing with autism or any type of Special need human. That’s where these people with these paper hanging on there walls ( Bachelor degree ) should start educating others how to help the proper way for Special need people. This Article is all False hope for autism.

This article doesn’t tell how many people were studied in total. In fact, the scientific study’s title is “…a mouse”. Singular. Everyone knows you need to have a large sample study in order to gain any type of conclusion. Nothing is conclusive here, in my opinion.

What those people with autism commenting here fail to realize is that this autism of a thing is a spectrum. All of you here are not having this condition as far as am concern. My son is 12 with a case of regressive autism has lost every single skill he previously acquired and is mostly inflicting injuries on himself can’t use the toilet, is out of school, infact I doubt if he aware that he is alive. So you expect me not to worry about finding way out? Please scientists go on with anything that will better the life of these children. If my child is high functioning like you guys, I will have nothing to worry about. So you need to realize that autism is a spectrum. It affects people differently.

People sitting talking smack about us “high functioning” (which we are not and don’t use that term for this reason) autistics, clearly aren’t seeing what the problem we have is. It’s not that we don’t know that this could benefit people with very high needs. We aren’t stupid. It’s more frustrating that we’ve been forgotten when it comes to autistic studies. They don’t ask us what we need help with to better understand our issues. As someone with a non verbal son with high needs, I know the struggle, but you aren’t the victim here, they are. I have to advocate for my son but I can’t get the same respect because I’m too “normal”. “High functioning” autistics are offin themselves at an alarming rate because we can’t stand to exist in a world that doesn’t care. Have some compassion on an issue you don’t fully understand.

This begs the question: Do we have to risk getting “The Bends” just because we stim or pace? For the father of the 12 year old who cannot use the toilet, do you think they can tolerate being in the chamber for who knows how long?

Judgmental. If you have autism and are happy with it than more power to you. However for some of us it is debilitating.

I looked up one of those chambers, no way am I getting into that claustrophobic thing. Like you keep trying to “cure” us but how about just try being nice perhaps? Being understanding and non-judgemental does loads more for my social anxiety than a pressure cooker ever will. Maybe we should work on curing societys rudeness first. Also, I only skimmed the article so it’s on me probably but what exactly is an autism animal model I’ve never heard that before

Not every autistic person is able to function like you are. My daughter is essentially nonverbal and has bad behavioral episodes caused by frustration by being unable to communicate her wants and needs. Something like this, if it works as they said, would make it 100000% easier on everyone. These types of therapy aren’t for everyone and are likely best for people that are so severe on the spectrum that they can’t even function on their own. Consider yourself blessed to be able to read, write and communicate with those around you in an understandable way. You don’t understand how helpful this would be to my family. I’d have a child that can actually understand what is being said to her and can respond back in some verbal and coherent form. I’d probably cry if she suddenly went from nonverbal to talking after 40hrs of this treatment. If it effectively stopped or extremely reduced her aggression and behavior episodes, I’d be ecstatic. And who wouldn’t be?? No more worries about her hurting teachers at school or potentially someone else cause she couldn’t control herself.

Our autistic daughter is frequently made miserable by her autism. She talks about her brain not letting her do what she wants, about being constantly frustrated by the way her autism affects her subjective experience of living in her own head.

We would do anything that *she* wanted, to help her feel better in the ways that *she* feels miserable. But, so far, we’ve all found limited success.

Not all people with autism are unhappy about it. And many people with autism are unhappy because of the way society treats people with autism. But *some* people with autism are miserable *because of their autism*, in ways that their context can do nothing to improve.

Please don’t exclude my daughter’s lived experience, in your perfectly understandable desire to push back against the way that our society pathologizes autism even when it causes no intrinsic distress in the person experiencing it. For some people, autism itself hurts. 😢

Some are missing the point of these treatments. My grdaughter is autistic but she does not socialize, speak unless directed right ar her, does not really know how it is to do anything without instruction. Some people leaving comments say they are autistic but they are able to read on their own and they know what they are reading. If my grdaughter could do that, I would not even consider her autistic.

This sounds like a gimmick. My sons and I have ASD my eldest and I are verbal and my youngest is not. He has agoraphobia issues so something like this chamber may scare the heck out of him. For those talking about people trying to change them I feel miss the point. I would accept any help for my kids and myself. While our thinking and perception is unique to ourselves, our health issues are not. By the time we reach adult hood 1 in 4 of us will acquire a neurological disease like Parkinson’s or dementia. I’m assuming it’s because our gut flora is highly dysfunctional and does not work properly ( Gut theory). Also compared with the neurotypical population our lifespans are much shorter. On average classical autism patients see to live up to 39 yrs of age where as people with aspbergers level diagnosis reach to see 57 on average. I would like to see our lifespan reach somewhat of a normal frame and is riddled with less neurological problems .

How does one do about being involved in the study as a participant?? I’d be genuinely interested to join along with my daughter and see the effects on us. I’m pretty sure I’m on the spectrum and my daughter is on the moderate to severe side with behavioral and nonverbal symptoms.

How lucky so many of those responders are who are aware of their diagnosis enough to make choices in and out of relationships! But they call it a Spectrum for a reason. For those un-diagnosed or unaware in neurodiverse relationships, further that may share other dx-s unaware or untreated, relationships and families are often destroyed in time. All that aside, for those becoming aware something is wrong and trying to identify it through therapy with the many angels beginning to specialize in the higher levels of the Spectrum, these researchers findings could be miracles for the future! Jobs, friendships, marriages, children who feel abandoned, I’ve seen it all. Look into AANE and read the forum emails! Join the groups. We NEED this research even if you don’t. Keep up your good work and self care. You’re clearly doing well and must be happy.

5 mg Lexapro was like someone blew 75% of his severe autism quirks away

This isn’t a new treatment for ASD, nor is it effective. It gives people false hope and may even cause more harm than good. There is not a shred of empirical evidence proving it to be effective. If there was then it would have been all over the news by now. It’s been around for well over a decade.

So they tested it on some autistic mice and one little girl. Promising.

My son has severe autism. He suffers daily from an inability to communicate, insomnia, chronic constipation, self-injury, aggression, and anxiety. He attacked me driving down the road related colon cramps. He sometimes withholds his stool for 21 days straight. Yes, I think he would love treatment to make his life 20-30 percent better. I love him more than anything in the world; it breaks my heart to watch how much he suffers. We do not live in a high-functioning world. Of course, I would do anything to take away his pain if it worked. Unfortunately, there are minimal options for people with severe autism that take them to even a moderate level of functioning. He will need daily living support probably for the rest of his life. It absolutely kills me to think of his life once I’m dead and gone. People like my son are vulnerable to predators. I hope they find more treatments that are humane to help him.

Very well said Zac 👏

Most of the children I see – who have autism or other issues would be traumatized by being places in such a chamber for an hour x 40. “The girl”? How old was she? In what way and to what degree did autism effect her? You can put a mouse in a hyperbaric chamber – no problem . How did you place this child in one?

Autism is not a disease. Stop trying to ‘treat’ it and maybe put all that time and effort into listening to actually autistic people and putting a stop to damaging nonsense like this. Jesus christ, people with so much education behind and yet they still don’t bloody get it.

Listen to the full R’s talk about ground breaking progress to help millions… like narcissistic children indoctrinated in new age anti progressive cult think akin to the psychological operation that is the manufactured trans/lgbtq societal gender war. “Are you saying im not perfect because I wont make eye contact, cant function in society and have been a tremendous burden on my loved ones who have fought an unwinnable fight my whole life, sacrificing theirs for mine… well words are violence and you’re racist. Dont assume my dogs gender. Im fine. We are fine. Neuro diversity is good and that kid not being able to talk… that builds character?” This is wonderful and if you think otherwise or feel personally attacked… head to the nearest pressurized chamber with a shower to wash the sand out.

I bought a hyperbaric chamber over 10 years ago for my then 6yr old son who was diagnosed on the lower end of the autism spectrum. He was doing ABA treatment at the time, I asked all the doctors and specialist back then about what I was researching and they told me that it was not going to work because autism is genetic, but he wasn’t barely progressing in ABA. Even my husband was a skeptic because we were spending almost $13,000 with conversion from $US to $CAD but I didn’t care because I refused to believe that nothing could be done for my son who was progressing normally and started regressing at age 2. Within a week of usage he went from barely 10 words per day to over 100 words the therapist were witnessing. He was potty trained a month later in 1 week never haven’t had an accident since, started reading in 6 months, changes in food choices in around a year and more importantly vast improvement in his behaviour. I tried telling them what I was doing but they didn’t think that hbot was helping so I stopped talking. What does a mother know, I am a not part of a university study. My son was later doing a university study where they were tracking his eye movements. I told them about the chamber nothing. So my son has improved and my information could have helped many parents years ago but now 10 years later this is a headline

This is great news. How is your child doing now? This gives me hope ❤

Maybe the school system should be more inclusive of neurodiversity. Idk. Just a thought. We grow up thinking that school is going to make us well rounded. But they want to keep defunding anything creative. Now we got a jacked left brain and a crippled right. School is a terrible atmosphere for autistic people. Probably because we know at a cellular level that the environment is soul crushing. I don’t think an oxygen chamber would change my mind about that, but this is very Ineresting and would love to hear more.

Not everyone who is autistic is a genius like Einstein. There are autistic people who are non verbal,unlettered, into repetitive, self harming behaviour like head banging, totally dependant on others for their day to day needs and not even aware of all this as they live in their own warped world of pain. If treatments like this one can help them, it would be a huge help for their caretakers. Autism is not cute or just a slight quirk, people!

I think this is an exceptional break through and that hopefully will lead to further break throughs. My son is autistic and I’m almost certain he would like the be neuro appropriate. As a mother of an autistic child, once I leave this world I don’t know for certain how he will be cared for. If he is able to cope socially, my fears will be lessened. Is this selfish, hell yes it is but if he cannot interact in a way to express his feelings to others, will this not cause him more frustration and cause him to withdrawal even more? It most definitely will. This doesn’t mean one has to be more social it just means he would have the ability should he choose to do so. More power to those who have made this discovery. Please don’t stop researching autism. We need you desperately.

My son is 11.5 years old. He barely reads at a kindergarten level and math at grade 1. He will not use any other toilet than home and its a fight to get him to let me clean him up afterwards. For this reason, we hardly leave home. His language is limited and jarbled. He self harms and has meltdowns over the smallest of issues, mainly eats the same 3 foods and will not try anything new, has sensory issues, will not cooperate with doctors or dentists. For those of you that feel he doesn’t need “fixed”, you are greatly mistaken. He probably will never be able to function on his own or support himself. In cases like his, the entire family is evolved. If this treatment could help him in anyway, I would go to earths end to do it. I really hope this therapy proves to be effective for our family could use the help.

Hello, I have twin Autistic sons, age 20.

One twin has a job, drives and works on social settings on his own now. He’s very happy!

Sadly, his brother is VERY LONELY and non verbal. He can push a few buttons on his speaking device.

When asked what he wants??? A FRIEND!

Every person is different. Every Autistic person is different.

Let’s not knock any research the may HELP. So many studies over the past 20 years…we’ve learned how to identify (in utero) in order to abort these children.

I’m grateful for any studies that may one day help my poor, sad son.

Thank you for reading. Ruby

There always has ti be morons in the comment section giving their worthless opinion to feel important. Autism is related to inflammation in the brain which is NOT NORMAL for a human body. So for those of you saying it’s who I am, I was born this way, is completely ignorant. That’s like saying someone who develops severe joint inflammation as a child, i.e. oligoarthritis will be ok with their life and refuse treatment. It is a disability and hinders one in different and important aspects of life that are not healthy. Whether you want to admit that or not. This is breakthrough treatment and will take a few years to “perfect”. All you other pessimists can wallow in your depression because you are antisocial and believe that I’d a healthy lifestyle.

“Fixing autism” shouldn’t be the goal, but reducing brain inflammation is always a good outcome.

All these people saying, “maybe I don’t want to be ‘fixed'”fixed. Ever think of those on the spectrum that are also IDor can never live on their own or have a functional life because of it? Ever think of the CHILDREN who are able to possibly grow up without any difficulties? Many young children with autism struggle so much with communicating with others that they harm themselves, others, their environment, bc they are so frustrated they can’t communicate or their sensory system is in overdrive all the time. It is literally my profession to work part of an autism team to determine intellectual adaptive skills and then help develop a behavioral plan. I see how this impedes a child’s ability to develop socially, academically,communicatively, cognitively, etc, and it can be extreme for more than your realize. Why would we force a child to grow up with so many struggles of they don’t have to? That’s like forcing a child to battle a disease alone. Schools and parents provide intervention services ask the time for children on the spectrum, treatment like this should be no different. And btw, it’s “people WITH autism” not “autistic people”. Autism may be part of you, but it doesn’t define you. YOU define you, autism or not. It may shape you, but it is not the core of you.

Saying that this is essentially your job, is very disheartening. As someone who is autistic. (we actually prefer autistic people, not “people with autism) it should be society that changes to benefit everybody. Not us who change to benefit society. You say you see the impacts daily, yet don’t recognize you’re continuing them. Autism should *not* be likened to a disease. If you truly actually care about the people you work with. Maybe listen to us, instead of things written about us, by Allistics.

So many comment and it’s clear that 99% of them didn’t even read the introduction in the study or they wouldn’t be making the comments they are making.

While pressure therapy has an effect I’m nervous what it really means. Overwhelming the senses with a perfectly even pressure may well seem calming on the surface but lead to deeper issues involving repressed experience to stimulus. Experiments which I conduct on myself are moving in the direction of being open to stimulus rather than further isolating myself from my body. I have had some success in confronting reservoirs of anger and moving past them to a state of mind resembling comfort. On the other hand I would be very interested to test oxygen treatments as I’m sure my mind body disconnect includes shallow breathing patterns that clearly induce extra anxiety.

people in these comments are making great points about autism not necessarily needing a cure. however, the therapy also alleviates inflammation, which is helpful

My son is 21 years old and I would love the opportunity for him. He’s 21 77lbs and non verbal.

Great, more people treating autism as a disease and not something that just is. This biased study also makes the assumption that the autistic brain doesn’t work as well as the Allistics. My gods its 2022 can we stop treating autism like it’s cancer, something to be eradicated??

This is horrifying and extremely worrying to discover this and money has been spent on this?! I hope no one forces autistic people to go through this. ABA and shock therapy is torture enough.

Autism is a different neurotype not a defect! More time should be spent on accommodating autistic people’s needs and making the world suitable for all neurotypes NOT trying to make autistic people neurotypical.

It’s not trying to make us more neurotypical, it’s an attempt to treat aspects that disable us and makes daily life extremely difficult. Stop trying to get in the way of autistic people getting help.

My son is autistic, wonderfully autistic. Although he has made amazing progress and highly functional…his social skills are not. He doesn’t have friends, nor enjoy any sports. I’ll never going to cheer him up in a basketball game, he will not be invited to friends parties, perhaps he’ll never have a family of his own. Gaby doesn’t need a cure, but deserves an opportunity to enjoy these little things that we take for granted.

Funny thing is psychology today and scientific American published articles around the same time condemning this kind of thinking about autism as a disease to cure.

Maybe this can also work for narcissism

This is a great example of how a neurotypical will read a study on neurodivergents and completely miss the point of the scientific study. It is not “The mutation” as the author puts it, it is a mutation, one mutation in one person of 43 known mutations and countless unknown. The more important thing is that the autoimmune portion, which is associated with many people, is treated. Oh wait we already knew if you killed the cells in animal immune systems that those cells would stop attacking parts of the body and make everything feel better for people with autoimmune disorders.

I’d like to know more about the animal models with autistic “mutations.” How was that determined? What were their characteristics before and after “treatment.” What species? What was the duration between the treatment and social interaction? How long did it last? How were the changes measured?

It seems to me that if an animal is confined to a pressure chamber that the mere isolation itself could cause a temporary change in behavior. I would think that being in the chamber would be anxiety inducing, so being let out of it could cause a feeling of relief and maybe even joy. Change in interactions with others may just be a response to not being isolated anymore.

This study should be replicated for people with fibromyalgia who an illness known to be liked to inflimmation in the brain.

I have a autistic child I love her the way she is and I am not putting her through something like that. She already went through a lot of blood test when she was a baby we found out she also has a thyroid condition to I have to give her medicine every day just so she can manage her weight and she does not speak and does not drink a open cup and does not yous silver ware and she is still in pull ups. But I still love her very much and I would like to see her learn without a machine or anything else in that category.

Autistic children seek pressure perhaps this meets this need and helps to relieve the internal pressure they may be feeling. I do not understand why a parent would want to leave their autistic children as is, do we love them less as they are? I hope not. They want friends and relationships I cannot imagine leaving them in such distress. I have seen children at all levels of autism. The anxiety they experience is heartbreaking. We as parents have a responsibility to give them a way to cope and survive. We, the parents, do not live forever and the world is not a kind place.

STOP TORTURING INNOCENT ANIMALS. EXPERIMENT WITH YOURSELF OR YOUR FAMILY MEMBERS

Look, I can empathize with those high functioning autists here who feel that society makes life difficult for them and are butthurt at every suggestion that autism could be healed. I’m a schizoid myself and have often been wronged by ignorant expectations from normies. But this time, you are wrong and doing harm to other autists, because not everyone is as lucky as you. Autism is, as we like to repeat, a spectrum, and it’s one that also includes people where it’s definitely not society’s fault that they can’t function in everyday life and where the only voice they – unable to present their case – have is that of their relatives (whose lives they make extremely difficult). It would be great to have a treatment for that (and if that also gives you the option (no one’s forcing you) to do social stuff easier than before, all the better). Please proritize that over your personal indignation over being called disabled (which technically you are, as you lack certain common abilities, even if you’re fine with that).

You are a beautiful soul. Thank you for this well thought out, heart felt reply. I also have a brilliant one in my life who is schizophrenic. Such an amazing person. I hate when life gets hard for her. She is kind and beautiful and doesn’t deserve it. You give me a lot of hope. God Bless you. ♥️

Interesting research. I don’t think that the chamber benefits are anything new though. Autism mothers have known this for a long time and many already get hyperbaric oxygen treatment for their kids or even have their own chambers at home. Would love to see this research lead to the availability of this treatment and equipment to the average person. I’m not a fan of the negative comments here. I have two with autism, one who is brilliant like Einstein and Elon but would love relief from anxiety and fitting in better. The other has terrible co-morbids and pain that we manage in unique ways but I think the oxygen therapy would help with being non verbal. It’s not lessening them in anyway to only want the best.

Austism is not genetic. Only ~8% of what happens to us is genetically caused. Also, if you wait for a “study” you’ll wait a long time. 99% of all studies prove exactly what the entity paying for the study wants proved so they can sell what they want to make millions on. Very simple equation. It’s like a business who sells Christmas lights, winter jackets, boots, and ladders, which then does a study and lo and behold, they learn to through this ‘”study”‘ that at homes where owners have purchased abc brand Christmas lights, winter jackets, boots and ladders always have the best looking Christmas lights every single year, only when they our base abc brands. This is how a very large percent of so-called studies in America are “designed.”

I don’t get the negative comments at all. Well maybe I do. I am a father of an autistic child, he is 9, he is high functioning. Obviously most of our friends are also parents to autistic children, I’m sure everyone here knows how that goes. But some our friends kids have severe issues and parents are very hopeful for any new treatment, especially non-instrusive treatments. It’s called the spectrum for a reason. We’ve been through a lot raising our kid, he’s came SO far at this point, but some of our friends are in hell, and want nothing more than for their kids to be more manageable, and excepted outside of the home. Blogs and commercials are total BS, it’s what happens in real life that pisses us special needs parents off. Bring on as many treatments as you can to help those parents that are in need of it. Just my opinion

I for one really appreciate this kind of experimentation and hope it leads to something great. I’ve always recognized my inability to properly recognize social cues and nuances and would love to partake in something that improved that.

My brother is 63 years old. He suffers from severe autism. It was a little known term in the 1960s and 70s. As a child I had to explain to people I didnt mean he is “artistic.” If a treatment would have stopped him from beating his face bloody it would have been a God send.

The article claims that the treatment is somehow more or less harmless.

“Harmless” and/or its synonyms are what they always say until it is shown that the treatments and proposed “cures” are actually very harmful!

So, the pressurized chamber works by forcing more Oxygen into the body and therefore more Oxygen into the Autistic person’s brain, eh?! Well, what if that would also cause OXYDATIVE STRESS AND/OR HYPER-PEROXIDATION THAT ACCELERATES THOSE AUTISTIC PERSONS” BRAINS’ AGING PROCESSES AND THUS WOULD DRASTICALLY INCERASE THEIR RISK OF ORGANIC (TRUE) DEMENTIA LATER IN LIFE — EH?!

Those so-called “scientists” are a bunch of Curebie Quacks and it shows!

Those Curebie Quacks of Tel Aviv really should stay away from Autistic people in all countries and of all nationalities! Israel would do well by eventually renouncing those Curebie Quacks — along with all the other Quacks. Also, the sooner that Israel renounces all Quacks, including Curebie Quacks, the better it will be for Israel’s moral and social condition!

That young Autistic girl was a child! What they essentially did to her was to perform a medical experiment on her, using elevated levels of Oxygen as a mind-altering drug or “psychotropic medication” (to use a euphemism). I understand that a certain creep named Mengele also liked to perform experiments with children!

I for one totally despise all Curebie Quacks! Curebie Quacks are evil and dangerous, and some of them are even genuinely sadistic in what they are willing to subject Autistic people to!

By the way, the very phrase “the autistic brain” is a very disturbing expression that symbolically dehumanizes Autistic people by suggesting that our brains be somehow not really Human brains. Imagine what it’s like to be told all your life that you are not fully or truly humsn because your brain is different from that of Joe Neurotupical’s brain! You might find it to be a hopeless and humiliating situation, right?

I suspect that the little girl in the experiment is being more sociable that usual because she wants those horrible treatments to end so that she can go home to go back to living her life! Or maybe she is/was experiencing some sort of Stockholm Syndrome or Trauma Bonding or some variations of those themes! See, she’s stll very young, so that’s why she’s acting more sociable and trying to please the Neurotypical normies. The day will very probably come in which she will see those Curebie Quacks and their accomplices for what they are: Bigots Who Like To Physically And/Or Psychologically Abuse Autistic Persons Under The Guises Of Science And/Or Healing !!!

I don’t think some of you people that are against this possible future therapy are thinking outside of your ‘boxes’. If you’re autistic and you’re capable enough to be typing on a comment section of this article then you may not need as intensive a treatment program as a lot of others out there that might benefit greatly from a treatment like this in the future. My middle child is almost 7 and isn’t talking yet. The prognosis for somebody like him isn’t nearly as good as somebody like my oldest son who’s 11 and is also on the spectrum but can communicate just fine and is sharp as a tack he’s just a bit goofy(aspergers). So I guess what I’m saying is just because you might be well enough to take care of your daily needs and communicate enough to get through life, there’s tens of thousands of others out there that don’t have those abilities and may never without breakthrough treatments like these coming out eventually, and there’s hundreds of thousands if not millions of loved ones of those people that would do anything to get them the help they need to be able to satisfy their daily needs themselves after we’ve passed on. It doesn’t mean ‘neurotypical’ people see autistic people as needing ‘fixed’, it just means we love them and want them to live satisfying and self sufficient lives when we’re no longer around to make sure that happens ourselves…

I understand this is not meant to cure autism, but to improve the quality life. Most parents of autistic children would do anything to get help for their kids. I, as a mother of an autistic child, am concerned about his safety when I’m not around. My Gaby is aware of his condition, he suffers, he does not have control for his outburst, he feels horrible when people get scared if him. Why not try something that promise some hope

Articles like this give me hope! All the neurodivergent folks should stop their inputs on treatments. Clearly they are not impacted as much and doing a lot of disservice to others on the spectrum.

And most autistic kids would need to be sedated to be locked in a chamber! wouldn’t that diminish the effect? Maybe there is another way to flood the brain with oxygen?

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December 5, 2023

This article has been reviewed according to Science X's editorial process and policies . Editors have highlighted the following attributes while ensuring the content's credibility:

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What we know about autism—and how to treat it—could change after new UCSF study

by Jason Fagone, San Francisco Chronicle

By fusing the power of artificial intelligence with new molecular techniques that also seem ripped from science fiction, researchers at UCSF have mapped the microscopic world of autism spectrum disorder in unprecedented detail, pointing toward possible therapies for a subset of patients who have specific genetic mutations, according to a new study.

"This opens up kind of a Goldilocks of potential treatment targets," said one of the study's authors, Matthew State, a UCSF child psychiatrist and geneticist. "It's an opportunity for shots on goal that we just have not had before, because of the complexity of autism."

The results are novel for a few reasons, researchers said. It's the first time that the cellular workings of a neuropsychiatric disorder like ASD have been explored this deeply, opening a door for similar investigations of other neuropsychiatric disorders such as attention deficit hyperactivity disorder and schizophrenia.

The study also combined a basket of new technologies in an original way. Those technologies include stem cells, CRISPR-based genetic tools and AlphaFold 2, the Google AI that predicts the behavior of proteins.

In addition, researchers leveraged a system originally developed at UCSF to study viruses, including the pandemic-causing coronavirus. That platform is able to create comprehensive maps of the interactions between proteins, the biological machines produced by genes that carry out work in the cell.

"We've been at the bleeding edge of putting all this together," said another study leader, Nevan Krogan, director of the Quantitative Biosciences Institute within UCSF's School of Pharmacy, which coordinated the research along with the Department of Psychiatry and Behavioral Sciences.

The paper was posted Monday on bioRxiv.org , a preprint server, and will be submitted to a peer-reviewed journal. UCSF's Jeremy Willsey and Tomasz Nowakowski co-led the work, and Rezo Therapeutics, a biotech company founded by QBI and Krogan, also contributed.

Over the last decade, scientists including State have discovered over 100 mutated genes that are connected to autism. But translating that knowledge into therapies has been difficult, State said. The brain is intricate, and just knowing the right genes isn't enough.

The UCSF-led team took a new approach, focusing on the proteins manufactured by those genes and mapping how they interact with each other.

Researchers found 1,000 proteins and more than 1,800 interactions. About 90% of the interactions "are things we've never seen before," State said.

The team then looked for clues about how the mutations lead to the disorder by using specific mutations from a subset of ASD patients. The scientists exploited AlphaFold's predictive abilities and various molecular techniques to pinpoint the most meaningful interactions, studying how those proteins function in human cells and in "brain organoids" grown from stem cells .

These findings could one day lead to new drugs for patients, State and Krogan said.

"We're shining a brand-new light on autism," Krogan said.

(c)2023 the San Francisco Chronicle Distributed by Tribune Content Agency, LLC.

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Cannabidiol in Treatment of Autism Spectrum Disorder: A Case Study

Affiliations.

• 1 Engineering Science, University of Toronto, Toronto, CAN.
• 2 Health Sciences, Wilfrid Laurier University, Toronto, CAN.
• 3 Family Medicine/Chronic Pain and Medical Cannabis, Private Practice, Toronto, CAN.
• PMID: 36176817
• PMCID: PMC9509693
• DOI: 10.7759/cureus.28442

This case study aims to demonstrate the use of cannabidiol (CBD) with low-dose tetrahydrocannabinol (THC) in managing symptoms associated with autism spectrum disorder (ASD) to increase the overall quality of life for these individuals and their families. ASD is a neurodevelopmental disorder affecting cognitive development, behavior, social communication, and motor skills. Despite the increasing awareness of ASD, there is still a lack of safe and effective treatment options. The study includes a nine-year-old male patient who was diagnosed with nonverbal ASD. He exhibited emotional outbursts, inappropriate behaviors, and social deficits including challenges in communicating his needs with others. Since the patient was unable to attain independence at school and at home, his condition was a significant burden to his caregivers. The patient was treated with full-spectrum high CBD and low THC oil formulation, with each milliliter containing 20 mg of CBD and <1 mg of THC. CBD oil starting dose was 0.1ml twice daily, increased every three to four days to 0.5ml twice daily. Overall, the patient experienced a reduction in negative behaviors, including violent outbursts, self-injurious behaviors, and sleep disruptions. There was an improvement in social interactions, concentration, and emotional stability. A combination of high CBD and low-dose THC oil was demonstrated to be an effective treatment option for managing symptoms associated with autism, leading to a better quality of life for both the patient and the caregivers.

Keywords: adolescent cannabis use; alternate therapy; autism spectrum disorder (asd); autism spectrum disorder and anxiety disorder; cannabidiol (cbd); cannabis (marijuana); child and adolescent psychiatry; pediatrics neurology; psychiatry; tetrahydrocannabinol (thc).

Copyright © 2022, Ma et al.

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• Case Reports

• Copy/Paste Link Link Copied

What are the treatments for autism?

There is currently no one standard treatment for autism spectrum disorder (ASD).

But there are many ways to help minimize the symptoms and maximize abilities. People who have ASD have the best chance of using all of their abilities and skills if they receive appropriate therapies and interventions.

The most effective therapies and interventions are often different for each person. However, most people with ASD respond best to highly structured and specialized programs. 1 In some cases, treatment can greatly reduce symptoms and help people with autism with daily activities.

Research shows that early diagnosis and interventions, such as during preschool or before, are more likely to have major positive effects on symptoms and later skills. Read more about early interventions for autism.

Because there can be overlap in symptoms between ASD and other disorders, such as attention deficit hyperactivity disorder (ADHD), 2 it's important that treatment focus on a person's specific needs, rather than the diagnostic label.

Select the links for more information on each type of treatment for ASD.

• Behavioral management therapy
• Cognitive behavior therapy
• Early intervention
• Educational and school-based therapies
• Joint attention therapy
• Medication treatment
• Nutritional therapy
• Occupational therapy
• Parent-mediated therapy
• Physical therapy
• Social skills training
• Speech-language therapy

If you have a question about treatment, talk to a health care provider who specializes in caring for people with ASD. These resources have more information about treatments for autism:

• The Centers for Disease Control and Prevention describes some treatment options. http://www.cdc.gov/ncbddd/autism/treatment.html
• National Institute of Mental Health. (2011). A parent's guide to autism spectrum disorder. Retrieved March 8, 2012, from http://www.nimh.nih.gov/health/publications/a-parents-guide-to-autism-spectrum-disorder/index.shtml
• Kotte, A., Joshi, G., Fried, R., Uchida, M., Spencer, A., Woodworth, K. Y., et al. (2013). Autistic traits in children with and without ADHD. Pediatrics, 132 (3), e612–e622.

College of Biological Sciences

New research suggests cerebellum may play important role in autism.

NIMH grant will fund studies on how autism risk gene impacts a crucial, but long-overlooked brain area

• by Douglas Fox
• April 02, 2024

Researchers in the College of Biological Sciences have received a grant to study the role of the cerebellum in autism. “We need a more holistic understanding of the brain circuits that drive this disorder,” says Alex Nord, an associate professor of neurobiology, physiology and behavior (NPB), and a researcher at the Center for Neuroscience (CNS). “The cerebellum is a key component that has been largely overlooked until recently.”

Nord partnered with Diasynou Fioravante, also an associate professor of NPB and CNS researcher, and received an R21 grant from the National Institute of Mental Health (NIMH). Announced in November, it will provide $435,000 of funding over the next two years.

With this grant, they will study how a potent autism risk gene, called chromodomain helicase DNA binding protein 8 ( Chd8 ), alters function in the cerebellum, which plays a crucial role in physical movement, and how this drives autism-like behaviors. Their research ties together two emerging trends in autism research.

Surprising discoveries in autism

Researchers long believed that autism involved genes that regulate communications between neurons — especially the synapses, where neurotransmitters carry signals from one neuron to another. But starting in the early 2010s, genetic studies revealed that many autism risk genes actually play a very different role: they encode proteins that reside far from the synapses — in the cell’s nucleus, where the DNA is located, and regulate the activity of hundreds of other genes.

“This was a huge surprise,” says Nord. Chd8 , a typical member of this group, regulates how tightly DNA is packaged and coiled with proteins. As such, it may regulate many genes that govern the formation and function of synapses.

At the same time, another major area of study is advancing the field of autism research. Scientists had assumed that autism was driven by changes in the cerebral cortex, which performs all sorts of tasks, such as recognizing words and faces, and “executive function” — controlling working memory, guiding our spotlight of attention, and making choices — such as whether to act on the impulse to withdraw one's hand when an unfamiliar dog approaches.

But in 2012, researchers reported that mice with mild abnormalities in the cerebellum developed behaviors that resembled autism in humans, such as reduced social interaction with other mice. “The autism field was really rocked by this discovery,” says Fioravante.

People had previously believed that the cerebellum mainly coordinates body movements such as walking, speaking, and typing. “When you damage the cerebellum, it causes profound movement problems, and this probably made it difficult to see more subtle changes in behavior,” says Fioravante.

But she points out that the cerebellum has significant connections with brain structures like the prefrontal cortex, which guides executive function, and limbic system, which regulates sociability, mood and emotions . People with cerebellar injuries often show autism-like changes in their emotions and social interactions.

Then in 2017, Nord and his colleagues reported a discovery that tied together these two intriguing threads : they found that the autism risk gene Chd8 helped guide the development of the cerebellum. Mice with one non-functioning copy of the gene had smaller cerebella.

That discovery “planted the idea of our project,” says Fioravante. She and Nord sat in offices next door to one another. And while Nord studied Chd8 , she worked on the cerebellum. In 2021 they applied for, and received, an earlier NIMH grant, to study how Chd8 influences the development of the cerebellum in mice, before and shortly after birth. Fioravante also received a pilot grant from the Behavioral Health Center of Excellence at UC Davis that launched Chd8 cerebellar studies in adult mice.

Working on these earlier grants from 2021 to 2023, they found that Chd8 mutations in mice triggered changes in the cerebellum and in behavior that resemble what is seen in humans with autism. For example, mice with a mutant copy of the gene had impaired social cognition. While regular mice prefer to explore and interact with mice they have not met before, mice with mutant Chd8 had more restricted interests — preferring mice or objects that they already knew.

New targets for treatment

With the new grant, Fioravante and Nord will pick up where they left off. In adult mice with normally developed cerebella, they will use genetic tools to disrupt Chd8 . They will examine how loss of Chd8 alters gene expression and function in neurons of the cerebellum, and how the connections between it and other brain areas change. They will also study whether disruption of Chd8 causes autism-like behavioral changes, such as reduced social interaction with other mice, or reduced interest in novelty. Cesar Canales, an assistant professional researcher in NPB, who has expertise in cerebellar anatomy, will take part in these studies.

These experiments “will help shed light on the totality of what the cerebellum does,” says Fioravante — getting beyond the traditional narrow view that it mainly coordinates movement. The team also hopes to uncover new strategies for treating autism.

Although autism involves early brain development, the condition usually isn’t diagnosed until children are years older — when the abnormal brain connections are already established, potentially making treatment difficult.

In these upcoming studies, Nord and Fioravante hope to explore whether the treatment window for autism can be extended. “If we see changes in behavior or neural circuits when Chd8 is disrupted in the developed cerebellum, then we know there is a treatment target,” says Nord.

These studies could also shed light on schizophrenia and obsessive-compulsive disorder, which occur more frequently in people with mutations in this gene, says Nord: “It’s a molecular handle, an entry point into the pathophysiology of these other complex diseases.”

Media Resources

• Douglas Fox is a freelance science writer based in the Bay Area.
• Fioravante Lab
• Germline Chd8 haploinsufficiency alters brain development in mouse ( Nature Neuroscience 2017)
• Cognitive-affective functions of the cerebellum ( The Journal of Neuroscience 2023)

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NHS faces ‘avalanche’ of demand for autism and ADHD services, thinktank warns

Nuffield Trust says system for treatment is ‘obsolete’ as number of patients in England awaiting assessment hits record high

The NHS is experiencing an “avalanche of need” over autism and attention deficit hyperactivity disorder (ADHD), but the system in place to cope with surging demand for assessments and treatments is “obsolete”, a health thinktank has warned.

There must be a “radical rethink” of how people with the conditions are cared for in England if the health service is to meet the rapidly expanding need for services, according to the Nuffield Trust.

The thinktank is calling for a “whole-system approach” across education, society and the NHS, amid changing social attitudes and better awareness of the conditions. It comes days after the NHS announced a major review of ADHD services .

Thea Stein, the chief executive of the Nuffield Trust, said: “The extraordinary, unpredicted and unprecedented rise in demand for autism assessments and ADHD treatments have completely overtaken the NHS’s capacity to meet them. It is frankly impossible to imagine how the system can grow fast enough to fulfil this demand.

“We shouldn’t underestimate what this means for children in particular: many schools expect an assessment and formal diagnosis to access support – and children and their families suffer while they wait.”

Figures published by NHS Digital last month revealed that the number of patients waiting for an autism assessment in England was at its highest level since current data started in April 2019.

Some 172,040 people were on waiting lists as of December 2023, up from 117,020 a year earlier and more than five times the 32,220 recorded in December 2019.

Although the National Institute for Health and Care Excellence (Nice) recommends that people with suspected autism should be diagnosed within three months of a referral, statistics show 147,070 patients had been waiting for at least 13 weeks in December, more than six times the 24,250 in December 2019.

New analysis of the data by the Nuffield Trust found that 79% of people who had been waiting 13 weeks or longer had not had their first appointment with a specialist, up from 44% in December 2019.

Between October and December last year, those who had had their first appointment had waited an average of nine months since referral. In December 2019 the wait was an average of four months, the thinktank says.

The Nuffield Trust also warned that the waiting times to be assessed for ADHD could be going unnoticed because of a lack of national published data. It said there had been a 51% rise in the number of people being prescribed medication for ADHD.

The analysis showed a 28% increase in drugs prescribed to 10-14-year-olds, as well as a 146% jump among 30-34-year-olds.

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“We are only now beginning to recognise just how many people are neurodiverse,” Stein said. “The challenge is that we have an obsolete health service model in place to deal with this avalanche of need. The huge rise detailed in our analysis is likely to be down to a combination of changing social attitudes and better awareness.

“We need to urgently understand the different elements of this complex picture and find a whole-system approach across education, society at large and the health service. Pumping more money into the current model certainly isn’t the solution: a radical rethink is required.”

An NHS spokesperson said: “The NHS is fully committed to supporting and improving the lives of those with ADHD and autism, which is why we have published new national guidance to help local areas to manage the 50% increase in referrals they have seen over last year.

“NHS England has also begun important work on investigating challenges in ADHD service provision and last month launched a cross-sector taskforce alongside government, to help provide a joined-up approach for the growing numbers of people coming forward for support.”

• Attention deficit hyperactivity disorder

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Grabrucker AM, editor. Autism Spectrum Disorders [Internet]. Brisbane (AU): Exon Publications; 2021 Aug 20. doi: 10.36255/exonpublications.autismspectrumdisorders.2021.diagnosis

Autism Spectrum Disorders [Internet].

Chapter 2 autism spectrum disorders: diagnosis and treatment.

Ronan Lordan , Cristiano Storni , and Chiara Alessia De Benedictis .

Affiliations

The diagnostic criteria and treatment approaches of autism spectrum disorders (ASD) have changed greatly over the years. Currently, diagnosis is conducted mainly by observational screening tools that measure a child’s social and cognitive abilities. The two main tools used in the diagnosis of ASD are DSM-5 and M-CHAT, which examine persistent deficits in interaction and social communication, and analyze responses to “yes/no” items that cover different developmental domains to formulate a diagnosis. Treatment depends on severity and comorbidities, which can include behavioral training, pharmacological use, and dietary supplement. Behavior-oriented treatments include a series of programs that aim to re-condition target behaviors, and develop vocational, social, cognitive, and living skills. However, to date, no single or combination treatments have been able to reverse ASD completely. This chapter provides an overview of the current diagnostic and treatment strategies of ASD.

• INTRODUCTION

Autism spectrum disorders (ASD) are complex, highly heritable neurodevelopmental diseases characterized by individuals with a combination of behavioral and cognitive impairments. These include impaired or diminished social communication skills, repetitive behaviors, and restricted sensory processing or interests ( 1 – 3 ). Swiss psychiatrist Eugen Bleuler first coined the term autism in 1908 to describe symptoms associated with severe schizophrenia, hallucinations, and unconscious fantasy in infants. Since then, the classification, diagnosis, and meaning of autism have radically changed ( 4 ). Between the 1940s and 1980s, ASD was described as abnormalities in language development, display of ritualistic and compulsive behaviors, and disturbance in interpersonal relationships. In the 1970s, sensory deficits in infancy were recognized in autistic children and became a defining feature of ASD ( 4 ). In 1980, the 3 rd edition of the American Psychiatric Association’s (APA) Diagnostic and Statistical Manual of Mental Disorders (DSM)-III), listed autism as a subgroup within the diagnostic category of pervasive developmental disorders (PDD) to convey the view that there is a broader spectrum of social communication deficits. The PPD contained four categories: infantile autism, childhood-onset PDD, residual autism, and an atypical form ( 5 ). At this point, it was recognized that the previously described symptomatology resembling schizophrenia was not a component of ASD because of the research conducted by Kolvin Rutter and others in the early 1970s. Consequently, childhood schizophrenia was excluded from DSM-III ( 1 , 4 ). In the 1980s, Wing and Gould placed autistic children on a continuum with other abnormal children and discussed autism in behavioral terms rather than psychosis ( 4 , 6 ).

Asperger’s syndrome, an ASD named after Hans Asperger, who first described its symptomatology in 1944, gained prominence in the ASD literature due to the works of psychiatrist Lorna Wing, who coined the term in 1976 ( 4 ). In 1981, Wing proposed that autism is part of a wider group of conditions that share commonalities, including impairments of communication, imagination, and social interactions. Asperger’s syndrome was eventually included in the DSM-IV in 1994 ( 7 ). In the mid to late 1980s, works by Simon Baron-Cohen, Uta Frith, and Alan Leslie led to the hypothesis that autistic children lacked “theory of mind”, which is the ability to attribute mental states to others and ourselves, an essential component of social interaction ( 8 ). In 1990, autism was first classified as a disability ( 9 ). Moving to the present day, due to the difficulty in defining and distinguishing between the various PDD, DSM-5 and the International Classification of Diseases 11 th revision use ‘ASD’ as a blanket term and distinguish individuals using clinical specifiers and modifiers ( 1 ). Our knowledge of pathology, etiology, and behavior of ASD continues to evolve. Nowadays, ASD is widely recognized as a somewhat common condition that, for many, but not all, requires lifelong support ( 2 ).

The diagnostic features historically associated with ASD are a triad of impaired social interactions, verbal and nonverbal communication deficits, and restricted, repetitive behavior patterns. These core features are observed irrespective of race, ethnicity, culture, or socioeconomic status. However, ASD individuals tend to differ from one another, so one feature may be more prevalent than another ( 2 , 10 ) (see Chapter 1 ). Despite recent advancements, there are currently no reliable biomarkers for ASD ( 11 ). Consequently, today’s clinical diagnosis of ASD is based on assessing behaviors as outlined in APA’s DSM-5 criteria ( 2 , 12 ). Other disorders that may co-occur with ASD. These include psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), which is considered the most common comorbidity in people with ASD (~ 28%) ( 13 ), along with other conditions and diseases including anxiety and phobias, dissociative disorders, depression, bipolar disorder, and episodic mood disorders ( 13 , 14 ). Physiological disorders (e.g., gastrointestinal disorders) and genetic disorders (e.g., fragile X syndrome) may also be prevalent ( 2 , 14 ).

Hallmarks of ASD and gender prevalence

In 2010, the prevalence of autism was estimated to be 1 in 132 individuals (7.6 per 1,000), affecting approximately 52 million people globally ( 15 ). However, estimates can vary due to the diagnostic methodologies used and the definition of ASD adopted in studies. It was approximated in 2016 that 1 in 54 children in the USA was diagnosed with ASD ( 16 ). Generally, there appears to be epidemiological evidence of ASD sexual dimorphism. ASD is more prevalent in males than females in a ratio of 3:1, ranging from 2:1 to 5:1 ( 17 ). However, it has been proposed that females are more likely to be diagnosed with ASD later than males or may never be diagnosed ( 18 ). Biological determinants are now under investigation to resolve whether females have better adaptation/compensatory behaviors or if diagnostic biases play a role ( 19 , 20 ).

Persistent issues with social communication can manifest in various contexts. For example, ASD individuals may persistently fail to hold a normal conversation or have an unorthodox approach to social situations. Some ASD individuals may also present deficits in non-verbal communication behaviors such as difficulty maintaining eye contact or abnormalities in using or understanding body language or gestures. ASD individuals may also have trouble understanding relationships or social interactions that may lead them to have difficulties developing and maintaining relationships ( 2 ). Repetitive or restricted behavioral patterns include movements, speech, play, use of objects, resistance to change, and insistence on sameness. In addition, fixations on certain interests with abnormal focus or intensity or periods of hyperactivity and hypoactivity in response to sensory inputs are also associated with ASD. These symptoms are mostly present in early life but may not fully manifest until social interaction is warranted. These symptoms can be somewhat masked later in life by coping strategies learned ( 2 ).

Early signs and symptoms

Early identification and evaluation of ASD in children has become an important public health objective due to the potential association between early intervention and improved development of children with ASD ( 21 – 23 ). Early presentation of ASD often occurs due to parental concerns spurred by recognizing some of the hallmarks of ASD previously outlined ( 24 ), which has increased due to greater awareness of ASD hallmarks among parents, healthcare specialists, and childcare workers ( 25 ). Some video studies suggest that it is possible to identify symptoms of ASD in children as young as 6–12 months old ( 26 , 27 ). There is increased interest to monitor the emergence of ASD prodromes such as reduced motor control or abnormal social development in the first year of life ( 24 , 28 ). As research has developed, it is now known that the prevalence of ASD is particularly high in preterm infants ( 29 ), indicating a requirement for additional vigilance in the preterm population.

Diagnostic tools

Numerous diagnostic guidelines of varying quality are available ( 30 ). The essential features of ASD diagnosis include observing a child’s relationship and exchange with their parents and with an individual unknown to the child during unstructured and structured assessment activities and a detailed history of the child’s development ( 1 ). ASD diagnosis can occur at any age but most frequently occurs early in childhood. Although there is a lack of a universal screening instruments, public health systems in various countries in Europe such as Spain and Ireland have programs in place to identify young children with ASD (~ 18–30 months) using M-CHAT (Modified Checklist for Autism in Toddlers) and similar tools ( 31 ). The sensitivity of these screening methods has been questioned as they fail to identify most children with ASD before their parents have already reported delayed development ( 32 ). There may also be racial disparities in early diagnosis of Black and Hispanic children versus white children, which has been reported in the United States. It was found that the first evaluation of ASD in Black children is less likely to occur by 36 months of age than in white children with ASD (40% early evaluation of black children versus 45% of white children) ( 33 ).

Inconsistencies aside, several standardized screening tools exist to diagnose ASD at an early age, many of which focus on high-risk individuals, e.g., with a family member previously diagnosed with ASD ( 24 ). These include the Screening Tool for Autism in Toddlers and Young Children (STAT™), a 20 min observation of young children, established in 2000. The longer and widely researched Autism Diagnostic Observation Schedule (ADOS™) is a 45 min observation conducted by a professional or clinician to diagnose ASD from 12 months to adulthood ( 31 ). There also exists screening tools suitable for research, such as the Diagnostic Instrument for Social Communication Disorders (DISCO) and the Autism Diagnostic Interview-Revised (ADI-R) ( 31 ) in the UK. Other screening tools such as the Social Responsiveness Scale (SRS), the Social Communication Questionnaire (SCQ), and the Childhood Autism Rating Scale (CARS) can be used to assess a child’s symptoms of ASD. While many tools to screen and diagnose ASD exist, two of the leading autism diagnostic tools in use today are DSM-5 and M-CHAT (Modified Checklist for Autism in Toddlers).

Since 2013, DSM-5 has been used as a diagnostic tool for ASD worldwide ( 1 , 12 ). According to DSM-5, to be diagnosed with ASD, a child must have persistent deficits in the following three areas of social communication and interaction: (i) social-emotional reciprocity; (ii) developing, understanding, and maintaining relationships; and (iii) nonverbal communication. In addition, at least two of the following four behaviors should be present: (i) inflexible to changes in routine; (ii) restrictive or fixated interests that may be abnormal in focus or intensity; (iii) hypo- or hyperactivity in response to sensory input or abnormal fixation with sensory aspects of the environment; and (iv) repetitive movements, speech, or use of items. Symptoms should be present early in the development (in some cases symptoms may be masked in early stages and become prevalent later) and cause clinically significant impairment of function. Finally, ASD may be suspected if the symptoms cannot be better explained by other causes of intellectual disability or developmental issues.

DSM-5 is unique in that it classifies ASD as a spectrum that now also includes Asperger’s syndrome. DSM-5 also recognizes that early symptom onset can occur or that the manifestations of ASD may not be recognized until later in childhood or even adulthood, even in those who were monitored early in life ( 34 ). Furthermore, under the repetitive and restrictive diagnoses domain, sensation-seeking behavior, and hypo-sensory and hyper-sensory responsiveness are now included in DSM-5 in contrast to earlier iterations ( 1 , 35 ). DSM-5 also allows for dual diagnoses of ASD and other comorbidities such as ADHD (28% of ASD individuals have ADHD) or other co-occurring conditions such as psychiatric disorders (e.g., anxiety, depression, aggression) or genetic disorders (e.g., fragile X syndrome) ( 31 ). As a result, DSM-5 is one of the most reliable diagnostic tools of ASD and is trusted internationally. DSM-5 is also used by the Centers for Disease Control and Prevention in the USA ( 30 ), UK’s National Institute for Health and Care Excellence Guideline ( 36 ), and New Zealand’s Autism Spectrum Disorder Guidelines ( 37 ).

M-CHAT, derived from the less sensitive Checklist for Autism in Toddlers (CHAT), and the less common Communication and Symbolic Behavior Scales (CSBS) ( 38 ) have become mainstream among parents and even professionals due to their low-cost and accessibility ( 39 ). M-CHAT is reliable and has been independently assessed in primary care settings ( 40 , 41 ). M-CHAT is available internationally in several different languages ( 42 , 43 ), and it can now even be accessed electronically via tablet devices ( 44 ). The M-CHAT is intended to screen children aged between 16 and 30 months. It contains 23 ‘yes/no’ items that span several developmental domains and encompasses an interview with parents to clarify parent questionnaires and reduce the possibility of false positives ( 24 ). This checklist relies on the parent’s report of the child’s behaviors and skills rather than the observations of a professional. Since 2009, the M-CHAT-revised with follow-up (M-CHAT-R/F) has been validated and is used widely ( 39 ). The M-CHAT-R/F) now has 20 ‘yes/no’ items, includes a component for a professional such as a clinician to review, and only necessitates a follow-up interview for those who are perceived to be of medium ASD risk ( 39 ).

Whether and to what extent ASD can or should be treated is a controversial topic, especially considering the noticeable heterogeneity within ASD children. Many approaches are available to improve the abilities and skills, and quality of life of individuals with ASD ( 45 – 48 ). These approaches involve families, clinical practitioners, and educators ( 49 ). However, to date, information on positive outcomes of a specific intervention, and the mechanism that leads to these improvements is scant ( 50 ). In this section, we provide an overview of the current interventional approaches to treat individuals with ASD.

Behavioral therapy

Depending on the severity and comorbidities, many treatment approaches are available but only a few of these approaches are considered ‘evidence-based’ with proven benefits ( 51 ).

Educational and behavioral interventions play a central role in addressing communication, social skills, play, daily living competencies, academic skills, and inappropriate behavior ( 52 – 54 ). The varied symptoms and functioning levels of autistic individuals requires individualized treatments ( 55 ). There is consensus on the importance of providing therapy as soon as possible, immediately after diagnosis or even in the case of suspected diagnosis ( 56 – 61 ). The involvement and training of parents ( 62 – 64 ), siblings, and peers are also important ( 65 ).

Applied Behavior Analysis (ABA) is one of the widely used evidence-based approaches ( 66 ). ABA interventions operate under the principle of re-conditioning target behavior. The main principle is breaking down specific skills or activities into small elements, and teaching these in a progressive and systematic manner through reinforcement. It has shown substantial improvements in language, IQ, and academic skills ( 67 , 68 ). Discrete Trial Training (DTT), Early Intensive Behavioral Interventions (EIBI), Pivotal Response Training (PRT), and Verbal Behavioral Intervention (VBI) are different types of ABA intervention. DTT is for preschool (3–5 years old) individuals, and it is conducted in a classroom setting ( 69 ). It breaks down learning outputs and uses trials of 5 parts to simplifying instructions and teach skills. The parts include cue, prompt, response, consequences, and inter-trial intervals to teach a desired response. EIBI are used for early detection in children who are younger than three years old. VBI involves various protocols that target language and speech ( 70 – 72 ). ABA and DDT are criticized for targeting certain behavior but not the inner motivations underlying such behavior, and its moderate effectiveness in adaptive behavior and socialization ( 73 ). Koegel et al. developed a more naturalistic approach to compensate for some of these limitations: the Pivotal Response Treatment (PRT) ( 73 ). While ABA is highly structured and led by a therapist, PRT targets key areas (rather than individual behavior) such as motivation, self-management, and initiative in social interaction through play-based and child-initiated activities. The goal is to produce a positive change in the pivotal behaviors that are supposed to lead to improvements in social, communication, and play skills. Often used to complement ABA or DTT approaches in structured settings, PRT is offered in natural environments.

TEACCH (Treatment and Education of Autistic and related Communication-Handicapped Children) is commonly used in association with ABA for early intervention ( 74 , 75 ). This framework was developed in the 70s by Scholper and colleagues. It targets the development of vocational, social, and living skills and teaches these skills in a structured environment where a sequence of activities is organized predictably, often associated with visual prompts (e.g., individualized visual schedules), to support the establishment of learning routines. TEACCH can be used across different environments.

Developmental models focus on teaching skills essential to a child’s development, such as emotional relationship and regulation, social communication, and various cognitive abilities. These models usually involve clinical observation of a child’s social responses, review of the child’s developmental history and evaluation of the child’s response to treatments, and in some cases, biomedical evaluation (e.g., genetics). Several developmental models are currently available that show positive outcomes: the Denver Model, the Early Start Denver Model (ESDM), the developmental individual difference (DIR), the Relationship developmental intervention (RDI), and the Responsive Teaching (RT).

The Denver model is one of the most studied developmental models developed initially by Rogers et al. ( 76 ). Therapists focus on deficit areas, particularly at the level of imitation, understanding and sharing emotions, theory of mind, and social perception but follow the developmental sequence of normally developed children. Interventions aim at creating a warm environment and positive relationship between children and adults. Teaching mainly occurs in naturalistic settings, involving parents as co-therapists. As the vital role of early intervention is widely acknowledged and the benefits of the Denver Model appreciated, the model has been adapted to toddlers and preschoolers, giving way to the ESDM. Significant improvements in adaptive behavior, language, and IQ were identified in randomized control trials ( 77 ).

DIR was developed by Dr. Greenspan in the 1980s and his focus was on ‘floor time’ and ‘child-led’ play. DIR also focuses on the child’s development. It comprises a series of strategies to enhance relationships and social/emotional communication to support cognitive and emotional development. Instead of identifying deficits, it focuses on meeting the child at his/her developmental levels (e.g., in terms of shared attention and self-regulation, engagement and relating, back and forth interactions and communications, play and symbolic thinking). It also acknowledges the different sensory and motor profiles of the individual by assessing and working on motor planning and sequencing, sensory processing (visual, auditory, proptioceptual), and modulation. Finally, it leverages the children’s strengths by establishing relationships and environments that support such strengths to develop emotional, social, and cognitive capabilities. Growing evidence seems to support this approach ( 74 , 78 ).

RDI focuses on activities that facilitate interactive behavior and positive engagement in social relationships to motivate the child to learn social skills and sustain social relationships ( 74 ). The program is based on the assumption that autistic children lack flexible thinking, and so it helps them develop dynamic intelligence to cope with changes and new information. RDI has six objectives: emotional referencing, social coordination, declarative language, flexible thinking, relational information processing, foresight and hindsight. Evaluations of this approach seem promising, showing reductions in autistic symptoms and increased mainstream placement ( 79 ).

Other developmental approaches under the label of “Skill-based developmental training” are also available. These include PECS (Picture Exchange Communication System) and PBS (Positive Behavior Support). PECS is used in children who are non-verbal as it is an augmentative communication system based on exchanging flashcards with images (replacing or integrating speech). It is based on the ABA principles of prompt, reinforce, reward success/correct, and error. Evidence supporting this approach is accumulating ( 80 ), but more evidence is needed ( 81 ). PBS is a comprehensive intervention that include ABA, normalization/inclusion movements, and person-centered values ( 82 ). The main goal is to help the children become more autonomous and less dependent on family members and therapists. One of the distinguishing features of this approach is the idea that changes must occur in the social system and the surrounding environment in which the individual is in, rather than the individual alone ( 83 ). This more ‘humanistic’ approach to treatment tries to focus on manipulating antecedent triggers to maladaptive behavior rather than showing the adverse effects of such behavior. Two PBS techniques have been developed: one is called the antecedent-based techniques ( 84 ) and involves the use of visual schedules to build activity patterns and offer choice ( 84 ), and the other focuses on understanding the problem behavior and developing educational strategies and reinforcements to improve lifestyle ( 85 ).

Several approaches with unproven benefits are also available. These include sensory integration therapy, auditory integration, music therapy, and animal-based therapy. Sensory integration therapy focuses on the neurophysiological processing of sensory information, which is known to be different in autistic individuals. The goal is not to teach a skill or correct behavior but to allow the child to interact with an environment in an adaptive way, thus developing a coping mechanism to correct the underlying sensory-motor dysfunctions ( 86 ). The treatment involves engagement of full body movements in environments designed to offer tactile, proprioceptive, gravitational, auditory, visual, and vestibular stimulation. Auditory integration therapy is based on sensory abnormalities and language disorders often associated with auditory issues. Treatment involves exposing children to filtered and modulated music (in terms of volume and pitch). It is based on the assumption that continued exposure to modulated sounds can functionally modify the central auditory processing system, thus impacting language and behavior ( 87 ). Animal-based therapy is another intervention that has generated enthusiasm ( 88 ). There are several types of animal-based intervention, involving dogs, horses, and dolphins. For example, dolphin-therapy consists of interacting with dolphins in captivity ( 51 ). It is believed that these animals can help humans communicate better with one another. Horse-riding therapy is another animal-based intervention based on the idea that it involves multiple functioning domains, including social, cognitive, and gross motor ( 89 ). It is also believed that the movements during riding help children self-regulate and demonstrate improvements in distractibility, attention, and social motivation ( 90 ). Horse-riding is also called exercise intervention (along with jogging, martial arts, swimming, or yoga/dance), which can result in improvements in numerous behavioral outcomes, including stereotypical behavior, social-emotional functioning, cognition, and attention ( 91 ). Music therapy is based on the assumption that certain processes in musical improvisation and coordination with other music players may help autistic individuals develop social interaction and communicative skills. Music therapy may help in the emotional and motivational responses of the involved individuals, though conclusive results are still lacking ( 92 ).

Pharmacological and dietary interventions

The most commonly prescribed drugs for individuals with ASD are Abilify (aripiprazole) and Risperdal (risperidone). While the FDA has approved these drugs for use in individuals with ASD, they have not been developed specifically to treat ASD. For example, aripiprazole is an atypical antipsychotic ( 93 ). In addition, comorbidities such as gastrointestinal problems (reflux, chronic constipation, and diarrhea) occur in 46–85% of children with ASD ( 94 , 95 ). Seizures occur in 11–39% of ASD cases ( 96 ). Sleep problems, depression, emotional reactions and behaviors, sinusitis, headaches, mood swings and bipolar disorders are other observed comorbidities ( 97 ). Melatonin could effectively treat sleep disturbance and insomnia by improving sleep onset ( 98 – 101 ). Pediatric insomnia is also treated using antihistamines, alpha-2-agonists, benzodiazepines, and chloral hydrate ( 102 ). In addition, valproic acid has been used to treat mood swings and bipolar disorders and seizures in people with ASD ( 103 ). Another drug for seizures is dimethylglycine ( 104 ).

The effects of chelation therapy with 2,3-dimercaptosuccinic acid (DMSA) or 2,3-dimercaptopropane-1-sulfonate (DMPS) to bind and eliminate heavy harmful metals ( 105 ), intravenous immunoglobulins to regulate immune response ( 106 , 107 ), and hyperbaric oxygen therapy to decrease the inflammation by increasing the oxygen levels ( 108 ) have been equivocal. Gastrointestinal therapy is a diet program that aims to introduce a gluten-free/casein-free diet, considering that peptides derived from gluten and casein may be involved in the origins of autism. No significant beneficial results were reported after this intervention ( 109 ). Diet interventions also include introducing vitamins and minerals to restore metal homeostasis, which is crucial for the normal neurodevelopment and brain function. Vitamins B6, C, magnesium, and Omega-3 fatty acids may be linked with improvements in the behavior of children with ASD ( 110 – 113 ).

Several experimental therapies are currently in development. For example, the use of ampakines in the treatment of ASD is presently investigated. Ampakines act as positive modulators of synaptic AMPA-type glutamate receptors. Pre-clinical studies have shown that the ampakines CX1837 and CX1739 can improve learning, memory, and social behaviors in animal models of ASD ( 114 ). Insulin-like growth factor 1 (IGF-1) is altered in ASD. Besides many other physiological functions, IGF-1 reduces inflammation by modulating cytokine levels and synapse function. IGF-1 was shown to have beneficial effects in Rett syndrome and ASD ( 115 , 116 ). Similarly, intranasal insulin has shown promising effects in children with Phelan McDermid Syndrome (22q13.3 deletion syndrome), a disorder with frequently occurring autistic behaviors ( 117 , 118 ). Insulin and IGF-1 activate insulin receptors. Intranasal insulin thereby modulates the Ras-MAPK pathway. Trofinetide (NNZ-2566), currently in phase 3 for Rett syndrome and phase 2 for Fragile X syndrome, is a modified form of glypromate, a protein fragment resulting from IGF-1 metabolism in the brain ( 119 ). AMO-01 is another RAS-MAPK modulator that has been shown to rescue the neuronal phenotype in multiple knockout mouse models of intellectual disability. This drug is currently in Phase 2 clinical trials ( 120 ). Thus, targeting IGF-1 signaling seems a promising strategy for the future treatment of ASD.

ASD is a lifelong condition that may result from different genetic and environmental factors. ASD phenotypes vary considerably from one person to another, complicating the diagnosis and treatment strategies. Although significant results have been achieved in the ASD diagnosis, there are no consistent ASD biomarkers at the moment. Over the years, the diagnostic tools have increased. Early identification of children with ASD allows selecting a suitable treatment to improve communication, social and living skills, and reduce maladaptive behaviors and comorbidities. Although significant progress has been made, the therapeutic options to treat individuals with ASD remain limited.

Acknowledgment: This research was supported by funding from NIH (NIH.3247) and NHC (Ref. No. VYB89). Ronan Lordan would like to thank Ms. Eimear Conway for her valuable discussions.

Conflict of interest: The authors declare no potential conflicts of interest with respect to research, authorship, and/or publication of this manuscript.

Copyright and permission statement: The authors confirm that the materials included in this chapter do not violate copyright laws. Where relevant, appropriate permissions have been obtained from the original copyright holder(s), and all original sources have been appropriately acknowledged or referenced.

Doi: https://doi ​.org/10.36255 ​/exonpublications ​.autismspectrumdisorders.2021.diagnosis

Licence: This open access article is licenced under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) https://creativecommons.org/licenses/by-nc/4.0/

• Cite this Page Lordan R, Storni C, De Benedictis CA. Autism Spectrum Disorders: Diagnosis and Treatment. In: Grabrucker AM, editor. Autism Spectrum Disorders [Internet]. Brisbane (AU): Exon Publications; 2021 Aug 20. Chapter 2. doi: 10.36255/exonpublications.autismspectrumdisorders.2021.diagnosis
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New Research Suggests Cerebellum May Play Important Role in Autism

Nimh grant will fund studies on how autism risk gene impacts a crucial, but long-overlooked brain area.

• by Douglas Fox
• April 02, 2024

Researchers in the College of Biological Sciences have received a grant to study the role of the cerebellum in autism. “ We need a more holistic understanding of the brain circuits that drive this disorder , ” says Alex Nord , an associate professor of neurobiology, physiology and behavior (NPB); psychiatry and behavioral sciences; and a core faculty member at the Center for Neuroscience (CNS). “ The cerebellum is a key component that has been largely overlooked until recently . ”

Nord partnered with Diasynou Fioravante , also an associate professor of NPB and core faculty member at CNS, and received an R21 grant from the National Institute of Mental Health (NIMH). Announced in November, it will provide $435,000 of funding over the next two years.

With this grant, they will study how a potent autism risk gene, called chromodomain helicase DNA binding protein 8 ( Chd8 ), alters function in the cerebellum, which plays a crucial role in physical movement, and how this drives autism-like behaviors. Their research ties together two emerging trends in autism research.

Surprising discoveries in autism

Researchers long believed that autism involved genes that regulate communications between neurons — especially the synapses, where neurotransmitters carry signals from one neuron to another. But starting in the early 2010s, genetic studies revealed that many autism risk genes actually play a very different role: they encode proteins that reside far from the synapses — in the cell ’s nucleus, where the DNA is located, and regulate the activity of hundreds of other genes.

“ This was a huge surprise , ” says Nord. Chd8 , a typical member of this group, regulates how tightly DNA is packaged and coiled with proteins. As such, it may regulate many genes that govern the formation and function of synapses.

At the same time, another major area of study is advancing the field of autism research. Scientists had assumed that autism was driven by changes in the cerebral cortex, which performs all sorts of tasks, such as recognizing words and faces, and “executive function” — controlling working memory, guiding our spotlight of attention, and making choices — such as whether to act on the impulse to withdraw one's hand when an unfamiliar dog approaches.

But in 2012, researchers reported that mice with mild abnormalities in the cerebellum developed behaviors that resembled autism in humans, such as reduced social interaction with other mice. “ The autism field was really rocked by this discovery , ” says Fioravante.

People had previously believed that the cerebellum mainly coordinates body movements such as walking, speaking, and typing. “ When you damage the cerebellum, it causes profound movement problems, and this probably made it difficult to see more subtle changes in behavior , ” says Fioravante.

But she points out that the cerebellum has significant connections with brain structures like the prefrontal cortex, which guides executive function, and limbic system, which regulates sociability, mood and emotions . People with cerebellar injuries often show autism-like changes in their emotions and social interactions.

Then in 2017, Nord and his colleagues reported a discovery that tied together these two intriguing threads : they found that the autism risk gene Chd8 helped guide the development of the cerebellum. Mice with one non-functioning copy of the gene had smaller cerebella.

That discovery “ planted the idea of our project , ” says Fioravante. She and Nord sat in offices next door to one another. And while Nord studied Chd8 , she worked on the cerebellum. In 2021 they applied for, and received, an earlier NIMH grant, to study how Chd8 influences the development of the cerebellum in mice, before and shortly after birth. Fioravante also received a pilot grant from the Behavioral Health Center of Excellence at UC Davis that launched Chd8 cerebellar studies in adult mice.

Working on these earlier grants from 2021 to 2023, they found that Chd8 mutations in mice triggered changes in the cerebellum and in behavior that resemble what is seen in humans with autism. For example, mice with a mutant copy of the gene had impaired social cognition. While regular mice prefer to explore and interact with mice they have not met before, mice with mutant Chd8 had more restricted interests — preferring mice or objects that they already knew.

New targets for treatment

With the new grant, Fioravante and Nord will pick up where they left off. In adult mice with normally developed cerebella, they will use genetic tools to disrupt Chd8 . They will examine how loss of Chd8 alters gene expression and function in neurons of the cerebellum, and how the connections between it and other brain areas change. They will also study whether disruption of Chd8 causes autism-like behavioral changes, such as reduced social interaction with other mice, or reduced interest in novelty. Cesar Canales, an assistant professional researcher in NPB, who has expertise in cerebellar anatomy, will take part in these studies.

These experiments “will help shed light on the totality of what the cerebellum does , ” says Fioravante — getting beyond the traditional narrow view that it mainly coordinates movement. The team also hopes to uncover new strategies for treating autism.

Although autism involves early brain development, the condition usually isn ’t diagnosed until children are years older — when the abnormal brain connections are already established, potentially making treatment difficult.

In these upcoming studies, Nord and Fioravante hope to explore whether the treatment window for autism can be extended. “ If we see changes in behavior or neural circuits when Chd8 is disrupted in the developed cerebellum, then we know there is a treatment target , ” says Nord.

These studies could also shed light on schizophrenia and obsessive-compulsive disorder, which occur more frequently in people with mutations in this gene, says Nord: “ It ’s a molecular handle , an entry point into the pathophysiology of these other complex diseases . ”

Media Resources

• Douglas Fox is a freelance science writer based in the Bay Area.
• Fioravante Lab
• Germline Chd8 haploinsufficiency alters brain development in mouse ( Nature Neuroscience 2017)
• Cognitive-affective functions of the cerebellum ( The Journal of Neuroscience 2023)

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