latest research on schizophrenia

Potential schizophrenia treatment, discovered at Vanderbilt and being developed by Neumora Therapeutics, entering Phase 1 clinical trial 

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Dec 4, 2023, 12:49 PM

A potential schizophrenia treatment discovered through the Warren Center for Neuroscience Drug Discovery has been cleared by the U.S. Food and Drug Administration for use in phase 1 clinical trials—the third WCNDD therapeutic to reach that benchmark.  

“Vanderbilt is proud that a discovery by our researchers at the Warren Center is now a significant step closer to helping improve the lives of people with schizophrenia,” Chancellor Daniel Diermeier said. “Our work with Neumora is the very definition of translational research and the work we aim to do every day, which is applying innovation and discovery to help address the world’s most complex challenges.”   

The clinical trial has been initiated by Neumora Therapeutics Inc. , a clinical-stage biopharmaceutical company founded to confront the global brain disease crisis by taking a fundamentally different approach to the way treatments are developed. Vanderbilt and Neumora signed an exclusive, worldwide license and a research collaboration agreement for two novel series of M4 receptor modulator compounds, including NMRA-266, in February 2022.  

Vanderbilt’s agreement with Neumora was centered around the M 4 muscarinic receptor, which NMRA-266 targets through positive allosteric modulation. In preclinical studies conducted by Conn and Lindsley, NMRA-266 was found to be highly selective to the M 4 receptor, the area of the brain that regulates neurotransmission of dopamine. Overactive transmission of dopamine is connected to the positive, negative and cognitive symptoms of schizophrenia.   

“The M 4 PAM story has been a Homer-style Odyssey to get to this point and represents almost 20 years of research funded by National Institutes of Health, the William K. Warren Foundation and pharmaceutical companies,” said Lindsley, also a University Professor of pharmacology, biochemistry and chemistry who holds the William K. Warren, Jr. Chair in Medicine. “This mechanism and NMRA-266 represent a potential game-changer for schizophrenic patients and their families. Moreover, this success is a testament to the virtue of academic drug discovery and Vanderbilt’s commitment to supporting the WCNDD, a clinical-stage biotech enterprise within the university.”  

For the WCNDD to have such regular production of clinical assets when up against diverse neuroscience pipeline is unprecedented among academic drug discovery centers, according to Lindsley.  

“NMRA-266 entering phase 1 trials highlights the complementary relationship between university researchers and industry partners,” said Vice Provost for Research and Innovation Padma Raghavan. “By pairing our faculty’s ingenuity with the private sector’s commercialization know-how, we are able to bring life-changing discoveries to patients in need faster.”  

Schizophrenia spectrum disorders affect 3.7 million U.S. adults, a figure up to three times higher than previously understood, according to a recent study . This fundamentally different mechanism that NMRA-266 acts through is very selective for brain circuits involved in schizophrenia, which means in is unlikely to have the adverse effects of current dopamine antagonists—resulting in an improved standard of care for people with schizophrenia.  

“The initiation of this phase 1 study is an important step in the development of NMRA-266. In pre-clinical studies NMRA-266 demonstrated a favorable pharmacologic profile that includes high potency and selectivity for the M 4  receptor subtype, meriting its advancement into the clinic,” Dr. Robert Lenz, executive vice president and head of research and development at Neumora, said in a  release . “With its pre-clinical profile and clinical validation of the M 4  muscarinic receptor class in treating schizophrenia, we believe that NMRA-266 has strong potential as a treatment for neuropsychiatric disorders.”  

Human clinical trials are a significant advancement in a five-step  drug development process . Drug discovery research begins in the lab and is followed by preclinical research to answer basic questions about safety. Then there is clinical research to ensure that the treatment is safe and effective. The FDA then reviews all submitted data. If approved, the therapeutic will be made available for use by the public and be monitored for safety by the FDA for as long as it is available.  

The Vanderbilt-Neumora collaboration was facilitated by the   Center for Technology Transfer and Commercialization . Vanderbilt researchers who contributed to research around NMRA-266 and the power of academic drug discovery include Darren W. Engers , Aaron Bender ,  Olivier Boutaud ,  Thomas Bridges , Julie Engers ,  Alison Gregro , Carrie Jones ,  Colleen Niswender ,  Jerri Rook and Kayla Temple .  

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Landmark study implicates specific genes in schizophrenia

Scientists analysed dna from more than 300,000 people with and without the psychiatric disorder.

The largest ever genetic study of schizophrenia has identified large numbers of specific genes that could play important roles in the psychiatric disorder.

A group of hundreds of researchers across 45 countries analysed DNA from 76,755 people with schizophrenia and 243,649 without it to better understand the genes and biological processes underpinning the condition.

The Psychiatric Genomics Consortium study, led by scientists at Cardiff University, found a much larger number of genetic links to schizophrenia than ever before, in 287 different regions of the genome, the human body's DNA blueprint.

Furthermore, they showed that genetic risk for schizophrenia is seen in genes concentrated in brain cells called neurons, but not in any other tissue or cell type, suggesting it is the biological role of these cells that is crucial in schizophrenia.

The research team say this global study sheds the strongest light yet on the genetic basis of schizophrenia. It is published today in the journal Nature .

"Previous research has shown associations between schizophrenia and many anonymous DNA sequences, but rarely has it been possible to link the findings to specific genes," said co-lead author Professor Michael O'Donovan, from the Division of Psychological Medicine and Clinical Neurosciences at Cardiff University.

"The present study not only vastly increased the number of those associations, but we have now been able to link many of them to specific genes, a necessary step in what remains a difficult journey towards understanding the causes of this disorder and identifying new treatments."

Schizophrenia is a serious psychiatric disorder that starts in late adolescence or early adulthood and at any one time affects around one in 300 people worldwide, according to the World Health Organization.

In the largest genome-wide association study to date, the research team identified a "substantial increase" in the number of genomic regions associated with schizophrenia. Within these regions, they then used advanced methods to identify 120 genes likely to contribute to the disorder.

As well as being the largest study of its kind, the researchers included more than 7,000 people with either African American or Latino ancestries in what they say is a small step towards making sure advances that come from genetic studies can benefit people beyond those of European ancestries.

Although there are large numbers of genetic variants involved in schizophrenia, the study showed they are concentrated in genes expressed in neurons, pointing to these cells as the most important site of pathology. The findings also suggest abnormal neuron function in schizophrenia affects many brain areas, which could explain its diverse symptoms, which can include hallucinations, delusions and problems with thinking clearly.

The team's ability to link to specific genes and areas of biology was enhanced by co-ordinating their work with a companion study involving many of the same scientists, including those from Cardiff University, led by the Broad Institute of Harvard and MIT, and published in Nature in parallel.

That study looked at mutations that, while very rare, have large effects on the small proportion of people that carry them, and found overlapping genes and overlapping aspects of biology.

Professor James Walters, co-lead author on the Cardiff-led paper and Director of the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University, said: "Whilst people with schizophrenia can recover, many do not respond well to treatments, experience long-term problems with their mental and physical health, as well as impacts on relationships, education and work.

"We hope the findings in this, and the companion studies, can be used to advance our understanding of the disorder and facilitate the development of radically new treatments. However, those processes are often not straightforward, and a lot of work by other neuroscientists is needed to translate the genetic findings into a detailed understanding of disease mechanisms."

The Psychiatric Genomics Consortium is funded by the National Institute of Mental Health (NIMH) of the USA and work in Cardiff was additionally supported by the Medical Research Council.

Dr Joshua Gordon, Director of NIMH, said: "These results, achieved through a global collaboration unprecedented in scope, mark an important step forward in our understanding of the origins of schizophrenia. The findings will allow researchers to focus on specific brain pathways in the ongoing hunt for novel therapies for this serious mental illness."

This study has demonstrated the importance and power of large samples in genetic studies to gain insights into psychiatric disorders. The team are now seeking to recruit more research participants and build larger, more diverse datasets to further advance our understanding of schizophrenia.

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Materials provided by Cardiff University . Note: Content may be edited for style and length.

Journal Reference :

• Vassily Trubetskoy et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia . Nature , 2022; DOI: 10.1038/s41586-022-04434-5

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The Pharmacologic Treatment of Schizophrenia—2021

• 1 Nathan Kline Institute for Psychiatric Research, NYU Langone Health, NYU Grossman School of Medicine, New York, New York
• 2 Associate Editor, JAMA
• JAMA Patient Page Schizophrenia Cara M. Borelli, DO; Hugo Solari, MD JAMA
• Original Investigation Comparative Effectiveness of Adjunctive Psychotropic Medications in Patients With Schizophrenia T. Scott Stroup, MD, MPH; Tobias Gerhard, PhD; Stephen Crystal, PhD; Cecilia Huang, PhD; Zhiqiang Tan, PhD; Melanie M. Wall, PhD; Chacku Mathai, AAS; Mark Olfson, MD, MPH JAMA Psychiatry
• Review Schizophrenia—An Overview Robert A. McCutcheon, MRCPsych; Tiago Reis Marques, PhD; Oliver D. Howes, PhD JAMA Psychiatry
• Viewpoint Ranking Antipsychotics for Efficacy and Safety in Schizophrenia Christoph U. Correll, MD; John M. Kane, MD JAMA Psychiatry

Schizophrenia is a chronic psychotic disorder with typical onset in early adulthood and a lifetime prevalence of approximately 1%. In addition to the hallmark symptoms of psychosis (delusions, hallucinations, disordered thinking), individuals may experience negative symptoms (apathy, loss of emotional expression) and cognitive deficits. In the past, people with schizophrenia often were confined life-long to psychiatric hospitals; however, the introduction of effective antipsychotic drugs, starting with chlorpromazine (Thorazine) in 1954, followed by the federal Community Mental Health Act of 1963 resulted in deinstitutionalization of an estimated 92% of hospitalized patients by 1994. Although outpatient treatment has been largely successful in allowing people with schizophrenia to live in the community, a shortage of treatment and rehabilitation services and housing, combined with reluctance of some to accept services, has contributed to high rates of homelessness and incarceration among those with schizophrenia in the US.

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Goff DC. The Pharmacologic Treatment of Schizophrenia—2021. JAMA. 2021;325(2):175–176. doi:10.1001/jama.2020.19048

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December 8, 2021

A potential new approach for the treatment of schizophrenia

by Wendy Bindeman , Vanderbilt University

A new study led by Jeff Conn, Lee E. Limbird Chair in Pharmacology, James Maksymetz, a former graduate student in the Conn laboratory, and other collaborators at the Warren Center for Neuroscience Drug Discovery has identified a protein in the central nervous system, known as mGlu1, as a potential target for novel treatments of schizophrenia.

Schizophrenia, which affects approximately 1 percent of the global population, has been historically difficult to treat. Current clinically approved antipsychotics are effective at reducing "positive symptoms" like hallucinations and delusions in some patients, but they fail to treat "negative symptoms," such as social withdrawal, lack of motivation and cognitive deficits associated with the disease. The new research focused on identifying a new approach that would treat positive and negative symptoms, Maksymetz said.

Schizophrenia is thought to occur when a region of the brain called the prefrontal cortex becomes abnormally active because interneurons, which connect neuron circuits or neuron groups, become dysfunctional and stop regulating neuronal activity. Conn's team sought to modulate the activity of those cells.

After identifying mGlu1—an abbreviation of metabotropic glutamate receptor subtype 1—as a potentially druggable target, they tested it with a compound that enhances its function: a positive allosteric modulator. The PAM was previously developed by Conn in close collaboration with other labs in the WCNDD, including those of Craig Lindsley, University Professor of Chemistry and Pharmacology, and Colleen Niswender, associate professor of pharmacology. Using this compound, they found that enhancing the activity of mGlu1 selectively increased the activity of specific inhibitory interneurons, restoring their ability to inhibit the neuronal circuits they control.

Further, the researchers saw that by working with the PAM, symptoms characteristic of schizophrenia in human patients were reversed. These results suggest that using a PAM to enhance mGlu1 activity is an effective treatment for schizophrenia.

Why it matters

Schizophrenia is an important clinical and societal concern. "Inadequate treatment responses and failures to address 'negative symptoms' and cognitive deficits result in poor patient outcomes," Maksymetz said. "And they incur a huge financial burden on the U.S. and global economies."

Researchers hope that this novel treatment strategy "may eventually provide relief for patients, allow them to reintegrate into and contribute to society, and diminish the burden on our health care systems." The results of this research are particularly exciting because the drug reverses working memory deficits, a hallmark of schizophrenia for which there is currently no treatment.

Today's pharmaceutical schizophrenia treatments were serendipitously discovered half a century ago and were not derived from good understanding of disease biology. Decades of clinical findings have improved researchers' understanding of the biological basis of the disease, opening the door for the development of better-targeted, more efficacious drugs. "We reasoned that if we addressed the underlying disease biology by boosting the function of these interneurons, then we might be able to rescue cognitive deficits associated with prefrontal cortex dysfunction," Maksymetz said.

What's next

The results of this study raise a number of questions about mGlu1 biology. Ongoing studies in the Conn lab are investigating the role and effects of mGlu1 in various regions within the brain.

To translate these findings to the clinic, scientists will need to investigate the efficacy of PAMs when used chronically rather than in the short term, evaluate potential side-effects, and determine whether enhancing mGlu1 reduces other symptoms in schizophrenia, especially "negative symptoms" like a lack of motivation and social withdrawal, which are frequently treatment -resistant.

"We think this study is a good foundation to build upon," Maksymetz said. "Hopefully we will be able to test the hypothesis that mGlu1 PAMs can actually treat patients with schizophrenia someday soon. I truly believe that understanding how neural circuits function and dysfunction will lead to a revolution in treating neuroscience-related diseases, and I'm excited to be a part of it."

The research was published in Cell Reports .

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Evidence Links Abnormally Formed Proteins With Schizophrenia Pathology in Some Patients

Posted: May 30, 2019

Research on Antioxidant Role in Schizophrenia and Psychosis Points to Possible Therapeutic Value of Compound Found in Broccoli

Posted: April 09, 2019

In a Comparison of Two Kinds of Cognitive Training, One Appeared to Help Schizophrenia Patients More

Posted: January 30, 2019

Adding Guanfacine Boosted Benefits of Cognitive Remediation Therapy in Schizophrenia Spectrum Disorder

Posted: January 14, 2019

Researchers Study ‘Background’ Mutations That Can Impact Schizophrenia and Autism

Posted: November 05, 2018

The Brain Continues to Develop in Young People With Schizophrenia

Posted: October 22, 2018

Computer-Delivered Cognitive Training Significantly Helped Schizophrenia Patients in Rehab Setting

Posted: October 17, 2018

A Revealing Genetic Comparison of Schizophrenia and Bipolar Disorder

Posted: October 09, 2018

Boosting Motivation and Cognitive Deficits in Mental Illness

Posted: September 11, 2018

Machine-learning Helped Identify Newly Diagnosed Schizophrenia Patients and Predicted Treatment Response

Posted: August 29, 2018

Medicinal Herb May Relieve Worsening Symptoms of Schizophrenia

Posted: August 13, 2018

“Disorganized Thinking” in Psychosis is Linked to Brain Processing Problem in Cerebellum

Posted: July 27, 2018

Study Suggests Cannabis Compound Can Make Schizophrenia Medication Less Effective

Posted: July 25, 2018

Folic Acid-Fortified Foods During Pregnancy May Support Child’s Brain Development After Birth

Posted: July 12, 2018

Genetic Variations Reveal Which Patients Will Have Cognitive Benefits From Antipsychotic Medications

Posted: June 26, 2018

Schizophrenia-Linked Genes Leave Developing Brains Vulnerable During Complicated Pregnancies

Posted: June 20, 2018

Impairments in Brain’s White Matter Linked to Core Cognitive Deficits in Schizophrenia

Posted: April 03, 2018

Large Gene Expression Study Sheds Light on Causal Factors in Five Brain Disorders

Posted: March 20, 2018

A 21st-Century Approach to Treating Psychosis and Other Adolescent Mental Health Disorders

Treating Psychosis Patients Early and Comprehensively Has Resulted in Improved Outcomes

Molecular Picture Points the Way to Better Antipsychotic Medications

Posted: March 12, 2018

NAC Medication Improves Working Memory in Schizophrenia and Bipolar Patients with Psychosis

Posted: February 26, 2018

Social Impairment Levels Remain Stable in Patients with Psychotic Disorders

Posted: February 05, 2018

Analysis Reveals Accelerated Rates at Which the Brain’s Gray and White Matter Deteriorate in Schizophrenia

Posted: November 28, 2017

Genome-Wide Studies Aid Investigation of Dual Diagnosis of Schizophrenia and Substance Use Disorder

Posted: November 07, 2017

Researchers Uncover Neural Circuit that Underlies Interest in Novelty

Posted: October 24, 2017

Studying Psychotic Symptoms in Marijuana Smokers at High Psychosis Risk

Posted: September 18, 2017

Research Shows ‘Exquisite’ Complexity of a Cell Network Regulating a Fear Circuit

Posted: August 29, 2017

New Calculator Helps Predict Risk of Developing Psychosis Across Diagnoses

Posted: July 18, 2017

New Technique Lets Researchers Watch Human Brain Circuits Begin to Wire-Up

Posted: June 26, 2017

Study Uncovers Role for Cerebellum in Cognitive Defects in Schizophrenia

Posted: June 05, 2017

New Class of Drugs Shows Promise for the Treatment of Schizophrenia in Animal Models

Posted: May 31, 2017

Study Reveals Weaker Brain Connections in Patients Who Did Not Receive Prompt Treatment for Psychosis

Posted: March 15, 2017

Diabetes Risk is Increased Even at the Start of Schizophrenia, Study Finds

Posted: February 22, 2017

Two New Studies Offer Alternative Explanation of Impaired Cognitive Function in Schizophrenia

Posted: February 15, 2017

Neurofeedback App Improves Early Cognitive Deficit in People with High Psychosis Risk

Posted: February 14, 2017

Study of Psychosis Relapses Among Schizophrenia Patients Suggests Preventive Potential of Frequent In-Person Check-ins

Posted: February 08, 2017

Sleep Disturbances Linked to Symptom Severity Among Those At High Risk for Psychotic Disorders

Posted: January 30, 2017

Research Indicates Cognitive Impairments are Early Symptoms of Psychotic Disorders

Posted: January 27, 2017

Mouse Study Reveals How Critical Connections Are Built in Early Brain

Posted: January 23, 2017

Blocking Overactive Enzyme Could Treat Schizophrenia Symptoms

Posted: January 19, 2017

New Research Defines Molecular Pathway That May Cause Psychosis in Some Types of Schizophrenia

Posted: January 10, 2017

New Way of Studying DNA as it’s Bundled in Cells Reveals New Schizophrenia Risk Genes

Posted: November 17, 2016

Researchers Catalog Subtle but Widespread Schizophrenia-Associated Differences in Gene Activity

Posted: November 02, 2016

Researchers Pinpoint Neurons That Cause and Maintain Wakefulness

Posted: September 30, 2016

New Technique Recreates Large-Scale Genetic Errors Linked to Neurodevelopmental Disorders

Posted: August 30, 2016

Study Finds Some Autism and Schizophrenia Related Genes May Also Be Involved in Bipolar Disorder

Posted: August 19, 2016

New Tool Calculates Patients’ Personal Psychosis Risk

Posted: July 27, 2016

Women Have More Gene Copy Number Variations Than Men, But This Doesn’t Increase Schizophrenia Risk as Expected

Posted: July 19, 2016

Doubt is Cast on the Contribution of Older Fathers’ Gene Mutations to Increased Mental Illness Risk in Their Children

Posted: July 13, 2016

Infections During Pregnancy Could Cause Developmental Disorders in Children

Posted: June 21, 2016

Prenatal Nicotine Exposure Raised Odds of Schizophrenia in Children

Posted: June 09, 2016

Gut Bacteria's Vital Role in Prefrontal Cortex, Brain's White Matter

Posted: May 24, 2016

Could Anti-Inflammatory Meds Prevent Immune-Linked Brain Disorders?

Posted: May 16, 2016

Blood Markers Indicate High Inflammation Levels in People with Schizophrenia, Bipolar Disorder and Depression

Posted: May 05, 2016

Researchers Reverse Cognitive and Behavioral Deficits in New Mouse Model for Schizophrenia

Posted: May 02, 2016

How Genes May Help Determine Response to Antipsychotic Medications

Posted: May 01, 2016

Testing a Simple Strategy To Prevent Schizophrenia via Dietary Supplements

New Biotypes Classify Psychosis Cases According to Measurable Biological Features

Onset of Psychotic Disorders Differs Among Ultra-High Risk Groups

Posted: April 29, 2016

Children’s Schizophrenia Risk Correlated with Their School Performance vs. Family Members

Posted: April 12, 2016

New Experiments Reveal Brain Circuitry Behind Inability to Experience Pleasure

Posted: April 05, 2016

Immune Activity During Pregnancy Tied to Neuronal Defects, Anxiety, and Cognitive Impairments

Posted: March 21, 2016

A Role for Spontaneous Mutations in the Development of Childhood-Onset Schizophrenia

Posted: March 07, 2016

Abnormalities in a Highly Duplicated Genome Region May Reveal Continuities in Symptoms of Schizophrenia and Autism

Posted: January 28, 2016

A Milestone in the Search for Schizophrenia’s Causes

Posted: January 15, 2016

Overactive Immune Cells Precede Schizophrenia Diagnosis

Posted: January 11, 2016

Animal Study Offers New Clues to the Genetics of Schizophrenia

Posted: December 01, 2015

Connectivity Problems May Indicate Which Individuals are at Greatest Risk for Schizophrenia

Posted: November 20, 2015

Imaging Studies Reveal Affected Brain Regions in Schizophrenia

Posted: November 06, 2015

New Insights into the Genetic Basis of Schizophrenia

Posted: October 22, 2015

Hopeful News on Comprehensive Team Treatment of Early Psychosis

Posted: August 26, 2015

Non-Invasive Stimulation Reworks Brain Waves, Improves Cognition

Posted: July 31, 2015

Genes Linked to Abnormal Brain Waves in Schizophrenia, Psychotic Bipolar Disorder

Posted: July 20, 2015

New Compounds Show Promise in Treating Schizophrenia Symptoms

Posted: July 15, 2015

Can Smoking Tobacco Lead to Schizophrenia?

Posted: July 07, 2015

Schizophrenia-Related Gene Mutation Impairs Fear Processing in Mice

Posted: July 06, 2015

Genetic and Brain Structure Abnormalities Linked in Schizophrenia

Posted: June 26, 2015

Innovative Analysis Finds Unique Brain Structure Patterns in People with Schizophrenia

Posted: June 23, 2015

Brain Connectivity Problems Linked with Psychotic Disorders are Present in Youth with Less Severe Symptoms

Posted: June 16, 2015

Large Study Confirms Major Hypotheses in Schizophrenia Research

Posted: June 09, 2015

Estrogen Drug Improves Cognition in Schizophrenia Patients

Posted: June 01, 2015

Large-Scale Gene Mutation Disrupts Brain Development During Key Period

Posted: May 18, 2015

Gene Associated With Cognitive Deficits a Possible Target For Drug Treatment

Posted: May 11, 2015

Genetic Disorder Points to Cellular Communication Problems in Schizophrenia

Posted: April 24, 2015

Tracing a Circuit Between Two Brain Areas Points To New Schizophrenia Treatment Targets

Posted: April 21, 2015

Three-Month Dosage of Injectable Antipsychotic Prevents Return of Schizophrenia Symptoms

Posted: April 13, 2015

Neurosteroid Treatment Reduces Schizophrenia-Like Symptoms in Mice

Posted: April 10, 2015

Understanding the Link Between White Matter Abnormalities and Schizophrenia Symptoms

Posted: April 06, 2015

Imaging Reveals Specific Brain Circuit Differences in a Subtype of Schizophrenia

Posted: March 23, 2015

Early Cognitive Decline Predicts Later Psychosis in Children With a DNA Deletion Syndrome

Posted: March 20, 2015

Digging Deeper into the Cause of Cognitive Deficits in Schizophrenia

Posted: March 17, 2015

New Clues About How Healthy Circuits Form in Developing Brains

Posted: March 10, 2015

New Clues About a Brain Receptor, a Neurotransmitter, and Schizophrenia

Posted: February 05, 2015

Study Finds Brain-Wave Increase in People With Schizophrenia

Posted: January 30, 2015

Multiple Psychiatric illnesses Share the Same Perturbed Biological Pathways

Posted: January 22, 2015

To Better Understand Mental Disorders, Researchers Reverse Engineer Schizophrenia “in a Dish”

Genetic signals emerging on schizophrenia risk, targeting the d1 dopamine receptor to improve working memory in schizotypal personality disorder.

Posted: January 21, 2015

Early-Stage Schizophrenia Associated With Increased Prefrontal Cortex Connectivity That is Reversed Following Treatment

Posted: January 20, 2015

Wiring Anomalies in the Fetal Brain Due To a Faulty Protein May Be a Causal Factor in Schizophrenia

Posted: January 08, 2015

New Pharmaceutical Approach Shows Potential Benefit in More Narrowly Targeting Antipsychotic Medicines

Posted: January 07, 2015

Problems with Attention Traced to Specific Brain Circuit

Posted: December 18, 2014

Researchers Discover New Regions of the Genome That Contribute to the Risk of Schizophrenia

Posted: December 09, 2014

IQ Study Finds Environmental and Genetic Factors in Schizophrenia Risk

Posted: December 03, 2014

Psychotic Symptoms in Young People Foreshadow Later Problems

Posted: November 22, 2014

Developing Risk Profiles for Schizophrenia

Posted: November 05, 2014

The Life of a Spine: Neuron Communication and Schizophrenia

Posted: October 23, 2014

What Causes the Placebo Effect in Clinical Trials of Antipsychotic Medications?

Posted: October 16, 2014

Study Offers New Insight into What Causes Learning Impairment in Schizophrenia

Posted: October 10, 2014

World Mental Health Day: “Living with Schizophrenia”

Posted: September 29, 2014

International Collaborative Effort Develops the Beginnings of a Blood Test for Psychosis

Posted: September 25, 2014

Stem Cell Technology Offers New Insight into Brain Mechanisms Underlying Schizophrenia

Posted: September 18, 2014

Bolstering Reading Skills Could Improve Outcomes in Schizophrenia

Posted: September 16, 2014

Electroconvulsive Therapy, with Clozapine, Shows Promise for Patients with Treatment-Resistant Schizophrenia

Posted: September 10, 2014

Finding Common Roots Across Spectrum of Psychosis May Improve Early Intervention Techniques

Posted: September 08, 2014

Congratulations to Mary-Claire King, Ph.D., Foundation Scientific Council Member, for 2014 Lasker Award!

Posted: September 04, 2014

Psychosocial Training Shows Promise as Supplemental Treatment for Schizophrenia

Posted: September 02, 2014

Resting State Brain Imaging Points to Differences in Early- and Late-Stage Schizophrenia

Posted: August 27, 2014

NARSAD Grantee Discovers Clues to New Pathways for Treatment of Schizophrenia

Posted: August 25, 2014

Can Antioxidants Help Prevent and /or Treat Symptoms of Schizophrenia?

Posted: August 21, 2014

With New Technology, Researchers See How Faulty Human Brain Cells Develop

Posted: August 15, 2014

Foundation-Funded Researcher Identifies Brain “Switchboard” that May Malfunction in Autism, Schizophrenia

Posted: August 08, 2014

Foundation-Supported Research Finds “Helper” Cells in Brain Actually Support Memory Function

Posted: July 25, 2014

“Reprogramming” of Genes Causes Some Symptoms of Mental Illness—May Be Reversible

Posted: July 22, 2014

Advancing Genetics Offer Promise for Developing Risk Profiles, Better Treatments for Schizophrenia

Posted: July 17, 2014

Maternal Infection, Inflammation during Pregnancy Linked to Baby's Risk for Schizophrenia

Posted: July 15, 2014

Stem Cell Technology Offers Rare Inside View of Brain Development and Schizophrenia

Posted: July 07, 2014

New Global Study Quantifies Risk of Mental Illness from Genetic Deletion Syndrome

Posted: July 03, 2014

Dr. Sanjay Gupta of CNN Quotes Foundation President in Articles on Schizophrenia

Posted: July 02, 2014

Gender Differences in the Adolescent Brain that May Link to Mental Illness

Posted: July 01, 2014

New Technique Identifies Genetic Underpinning of Disrupted Brain Connectivity in Schizophrenia

Posted: June 20, 2014

Researchers Complete Picture of How Brain Mechanism Linked to Depression, Schizophrenia Functions

Posted: June 19, 2014

Gene Linked to Bipolar Disorder, Schizophrenia Plays Key Role in Brain Development

Posted: June 17, 2014

NARSAD Grantees Advance Knowledge of Genetics and Early Brain Development in Schizophrenia

Posted: June 05, 2014

Released Today: New Insight into Root Cause of Auditory Hallucinations in Schizophrenia

Posted: June 02, 2014

Foundation-Funded Research Suggests Prenatal Beginnings of Schizophrenia, Could Aid Early Diagnosis

Posted: May 30, 2014

Genetic Sequencing Technology Helps Identify Mutations Linked to Development of Schizophrenia

Posted: May 19, 2014

Transplanting Brain Cells, Researchers Discover Potential Approach to Treat or Prevent Psychosis

Posted: May 08, 2014

Novel Approach Leads to Discovery of Disruption in Brain Connectivity in Schizophrenia

Posted: April 30, 2014

Study on Genetic Variability in Schizophrenia May Improve Prevention and Treatment Strategies

Posted: April 17, 2014

Foundation-Supported Research Advances Technology to Study Developmental Mechanisms of Schizophrenia

Posted: April 10, 2014

Misfiring Brain Signals in Schizophrenia Distort View of Reality

Posted: April 07, 2014

NARSAD Grantee Finds Experimental Compound Reverses Schizophrenia Symptoms in Mice

Posted: March 19, 2014

Brain Mapping Furthers Understanding of Why Imitation is Difficult in Schizophrenia

Posted: March 17, 2014

Scalp EEG Test May Be Able to Predict Future Psychosis

Posted: March 10, 2014

Genetic Analysis Offers New Insight into Memory Impairment in Schizophrenia

Posted: March 07, 2014

NARSAD Grantee Develops 3-D Picture of Protein Important in Schizophrenia

Posted: March 05, 2014

Integrated Approaches to Develop Improved Schizophrenia Therapies

Fine-tuning the circuitry in the brain and intervening early on: exciting next-generation treatment possibilities.

Posted: February 13, 2014

Crossed Wires in the Brain as Potentially Reversible Cause of Schizophrenia

Posted: January 27, 2014

New Understanding of Genetics Behind Schizophrenia From International, Collaborative Research Efforts

Effective brain communication impeded by “new” genetic mutations, progress in identifying sets of genes linked to schizophrenia, solving the schizophrenia puzzle, what makes some genes disrupt brain development, next generation therapies for schizophrenia: from specific genetic mutations to targeting repair pathways.

Posted: January 17, 2014

2013 Baer Prizewinner With a Dream: "To Re-Connect the Soul to the Mind... the Soul to the Brain" - Watch Video

Posted: January 13, 2014

New Technology Assesses Brain Plasticity, May Help with Schizophrenia, Depression

Posted: January 09, 2014

New Research Shows “Jumping Genes” Could Contribute to Schizophrenia

Posted: January 02, 2014

2013 NARSAD Grant Supports Discovery of Genetic Overlap Between Schizophrenia and Cognitive Ability

Posted: December 17, 2013

NARSAD Grant Furthers Exploration of Link between Older Fathers and Mental Illness

Posted: December 16, 2013

NARSAD Young Investigator Grantee Invents New Technology to Study Brain Plasticity

Posted: December 12, 2013

Chicken or Egg? New Research Shows Men and Women’s Brains are Wired Differently

Posted: December 02, 2013

Why do Antibodies Found in the Blood Only Sometimes Link to Neuropsychiatric Illness?

Posted: November 22, 2013

Discovery of First Genetic Protective Factor for Schizophrenia

Posted: October 25, 2013

Esteemed Schizophrenia Researcher, Marc G. Caron, Awarded with 2013 Lieber Prize

Posted: October 24, 2013

Electrical Stimulation Can Improve Cognitive Performance―May Help in Schizophrenia, Bipolar Disorder

Posted: October 23, 2013

Founding Foundation Scientific Council Member Awarded International Mental Health Prize

Posted: October 22, 2013

Researchers Find Way to Increase Neuroplasticity and Treat “Negative” Symptoms of Schizophrenia

State of md supports foundation scientific council member’s early intervention in psychosis program.

Posted: October 21, 2013

Looking for What May Cause Disordered Thinking (“Cognitive Deficits”) in Schizophrenia

Posted: October 08, 2013

Defining Psychotic Disorders―Mood Disorders and Schizophrenia―by Symptom Course and Long-Term Outcome

Posted: October 04, 2013

Pre-Term Birth Associated with Higher Risk of Mental Illness, But Also for Siblings

Posted: September 26, 2013

Long-Term Study of Children Shows Progressive Nature of Thinking Difficulties in Schizophrenia

Posted: August 15, 2013

New Schizophrenia Genes Discovered Through Innovative Genetic Sequencing Approach

Serotonin discovery via x-ray crystallography points toward more precise treatments.

Posted: August 02, 2013

Parent’s Diet May Impact Child’s Mental Health Shows NARSAD Grantee Generational Study

Posted: July 18, 2013

Genetic Sequencing Technology Helps Uncover New Potential Causes of Schizophrenia

Posted: July 16, 2013

Foundation Grantees Link Oxidative Stress with Mental Illness Risk Gene

Posted: July 05, 2013

Brain & Behavior Research Foundation-Funded Study Links Schizophrenia, Inflammation & Bacteria

Posted: July 03, 2013

Is Smoking Self Medication? New NARSAD Grant Research Provides Critical Insights

Posted: July 01, 2013

NARSAD Grant-Funded Discoveries Offer New Treatment Target for Schizophrenia

Posted: June 27, 2013

NARSAD Grantees Discover Potential for Treatment to Reverse Schizophrenia Symptoms

Posted: June 24, 2013

NARSAD Grantee Co-Leads Mammoth Effort to Dissect Mental Illness Risk Gene

Posted: June 20, 2013

NARSAD Grant-Funded Research Helps Identify Mechanisms To Improve Schizophrenia Treatment

Posted: June 14, 2013

Discovery Using Optogenetics May Help Fine-Tune Treatments for Schizophrenia Symptoms

Posted: June 10, 2013

New Computational Method Helps Decode Complex Circuitry of the Brain

Posted: June 07, 2013

Cutting-Edge Stem Cell Technology Offers New Insight Into Development of Schizophrenia

Posted: June 06, 2013

Relapse & Antipsychotic Treatment in Schizophrenia Change Brain

Posted: May 30, 2013

NARSAD Grantees Reverse Schizophrenia Symptoms in Adult Animals

Posted: May 21, 2013

Damaged Protective ‘Net’ May Cause Malfunction in Brain Cells in Schizophrenia

Posted: May 13, 2013

FDA Expedites New Psychosis Treatment Developed by Scientific Council Member

Posted: May 09, 2013

A New Window to Study Mental Illness: Stem Cells Converted to Brain Cells

Posted: May 02, 2013

The Nose May Know: Study Finds New Potential Way to Diagnose Schizophrenia

Posted: April 29, 2013

Foundation-Funded Study Identifies Schizophrenia Early Warning Sign

Posted: April 18, 2013

How Studies With Children Are Helping Identify Early Developmental Links to Mental Illness

Intervening in early psychosis with computer-based brain training.

Posted: April 17, 2013

NARSAD Grantee Maps Brain Navigation – Insights May Help Treat Schizophrenia

Posted: April 16, 2013

Understanding Healthy Brain Function Furthers Progress in Identifying Causes of Schizophrenia

Posted: April 03, 2013

New Schizophrenia Genes Discovered Through Innovative Genetic Sequencing

Posted: March 29, 2013

NARSAD Grantees Link Altered Brain Activity to Schizophrenia Cognitive Symptoms

Posted: March 21, 2013

New Technology Enables New Insights Pointing toward Safer Schizophrenia Medications

Posted: March 14, 2013

NARSAD Grant-Funded TMS Now Found Effective in Treating Schizophrenia Symptoms

Posted: March 12, 2013

NARSAD Grantee Discovers Predictor of Psychosis in Bipolar Disorder, Schizophrenia

Posted: March 06, 2013

Single Gene Plays Defining Role in Schizophrenia Symptoms and Outcomes

Posted: March 01, 2013

Recovery Interventions that Promote Productive Lives

Posted: February 25, 2013

NARSAD Grantee Helps Uncover Schizophrenia Warning Sign

Posted: February 19, 2013

NARSAD Grantee ‘2012 Editor’s Choice’ for Work on Recovery from Schizophrenia

Posted: February 12, 2013

Discovery Links Inflammation to Schizophrenia Onset, May Aid Early Intervention/Prevention

Posted: February 07, 2013

Foundation Grantees Develop Brain Atlas to Aid Understanding of Autism, Schizophrenia

Posted: February 01, 2013

Identifying What Keeps Electrical Impulses in the Brain Balanced—Linked to Schizophrenia

Posted: January 25, 2013

NARSAD Grant-Funded Research Identifies New Genetic Link to Development of Schizophrenia

Posted: January 21, 2013

Foundation-Funded Research Helps Identify How Adolescent Stress Can Cause Mental Illness

Posted: January 18, 2013

Schizophrenia Research Forum Features Paper with Discoveries on Genetic Deletion Syndrome

Posted: January 15, 2013

Released Today: Supplement Shows Promise for Preventing Schizophrenia

Posted: January 14, 2013

Learning About Individual Genetics Alleviates Suffering for Patients with Schizophrenia

Posted: December 27, 2012

2012 Highlights: A Sampling of NARSAD Grants at Work

Posted: December 17, 2012

Cells and Circuits: Neurotransmission with a Focus on Dopamine

Cognitive remediation activates neuroplasticity and improves social cognition in schizophrenia.

Posted: November 30, 2012

NARSAD Grantees Lead Study Pointing To Novel Pathways for Treatment of Schizophrenia

Posted: November 29, 2012

2008 Lieber Prizewinner Wins 2013 Grawemeyer Award for Schizophrenia Research

Posted: November 27, 2012

NARSAD Grant-Funded Research Furthers Understanding of What Makes Us Human

Posted: November 26, 2012

Dr. Walters Receives Sidney R. Baer, Jr. Prize for Innovative Schizophrenia Research

Posted: November 02, 2012

Dr. Michael Owen Recognized for Outstanding Achievement in Schizophrenia Research

Narsad grant-funded research identifies where empathy originates in the brain.

Posted: November 01, 2012

Prestigious Lieber Prize for Schizophrenia Research Goes to Dr. Michael O’Donovan

Posted: October 15, 2012

NARSAD Grantee Identifies New Pathway to Treat Schizophrenia

Posted: October 11, 2012

NARSAD Grantees Identify New Genetic Mutations that Cause Schizophrenia

Posted: September 24, 2012

Premature Birth Heightens Risk for Mental Illness

Comprehensive identification of key genetic players in schizophrenia, a natural laboratory: using an isolated population to study schizophrenia genes, translating epigenetics into novel therapies for autism and schizophrenia.

Posted: August 23, 2012

NY Times: New Study Confirming Risk of Autism and Schizophrenia Increases with Father’s Age

Posted: August 07, 2012

Creating a New Window to Study Synaptic (Dys)Function in Brain and Behavior Disorders

Posted: July 20, 2012

NARSAD Grantee Leads Team That Links Two Risk Factors for Schizophrenia

Posted: July 05, 2012

NARSAD Grant-funded Research Finds Links Between Schizophrenia, Bipolar and Autism

Posted: July 03, 2012

NARSAD Grantee Discusses Innovative Work to Understand and Better Treat Mental Illnesses

Posted: June 28, 2012

FDA to Evaluate Computer-Based Treatment for Cognitive Symptoms in Schizophrenia

Posted: June 19, 2012

NARSAD Grant-Funded Research Identifies Genetic Links in Weight Gain from Antipsychotics

Posted: June 04, 2012

NARSAD Grant-Funded Research Finds Premature Birth Increases Risk for Mental Illness

Posted: May 17, 2012

NARSAD Grantee Leads Breakthrough Research that Identifies the Genetic Code of Schizophrenia

Posted: March 29, 2012

New Discovery On Link Between Early Life Stress and Genetic Susceptibility in Schizophrenia

Posted: March 20, 2012

New Computer Program Improves Behavioral Symptoms and Brain Activity in Schizophrenia

Posted: March 12, 2012

25 Years of Outstanding Schizophrenia Research: The Lieber Prize

Posted: February 29, 2012

NARSAD Grantees Make Breakthrough to Improve Cognition in Schizophrenia

Posted: February 07, 2012

Scientific Council Member Outlines the Progress in – and Need for – Mental Health Research

Posted: January 20, 2012

SC Member Makes Discovery About Teen Susceptibility to Depression and Schizophrenia

Posted: January 19, 2012

A New, Quick Approach to Predict Future Course of Psychosis

Posted: January 06, 2012

Foundation-funded Discovery: Early Childhood Immigration Linked to Psychotic Disorders

Posted: January 05, 2012

NARSAD Grantee Makes New Discovery About Brain Malfunction in Schizophrenia

Posted: December 30, 2011

Basic Research and Novel Therapeutic Treatments Pave the Road to Cures for Mental Illness

Posted: December 05, 2011

Foundation Web-based Schizophrenia Research Forum Honored by ACNP

Posted: November 30, 2011

A Scientist Writes About Autism, Schizophrenia and their Causes

Posted: November 29, 2011

Foundation-funded Investigator Honored for Mental Illness Research Achievements

Posted: November 21, 2011

World-Renowned Investigator’s Personal Connection to Schizophrenia

Posted: November 18, 2011

BBC “Mental Health Revolution” Features Foundation-Funded Psychiatry Research

Posted: November 15, 2011

Coping with Psychosis: Using CBT to Manage Persistent Symptoms

‘father of cbt’ demonstrates its effectiveness treating low-functioning schizophrenia patients, genome-wide studies identify 11 new genetic links to schizophrenia and bipolar disorder.

Posted: November 09, 2011

Breakthrough in Schizophrenia Research by Foundation's 2011 Outstanding Prizewinner

Posted: November 03, 2011

Scientific Council Member Leads Effort that Reprograms Skin Cells to Grow Brain Cells in Lab

Brain & behavior research foundation scientific council member discovers key dopamine receptor structure.

Posted: October 24, 2011

New Understanding of Autism and Schizophrenia in Adolescence?

Posted: October 10, 2011

Outstanding Achievement Prizewinner Makes Discovery, Progressing Research for New Schizophrenia Treatments

Posted: October 06, 2011

NY Times Features Breakthrough in Treatment of Schizophrenia by Foundation-funded Scientist

Posted: October 03, 2011

A “GPS” System for Brain Cells is Created by 2011 NARSAD Distinguished Investigator Grantee

Posted: September 26, 2011

Understanding Why Identical Twins Are Not Carbon Copies in Mental Illness

Posted: September 22, 2011

Foundation Honors Scientists For Outstanding Achievements in Mental Illness Research

Posted: September 15, 2011

The Saturday Evening Post features NARSAD Grantees’ breakthrough insight on link between maternal infection and mental illness

Posted: August 26, 2011

NARSAD Distinguished Investigator Demonstrates Working Memory Can Be Restored in Elderly Primates

Foundation-funded discovery points toward genetic networks that predispose to schizophrenia.

Posted: July 26, 2011

Foundation-funded Study Supports Hypothesis That Davunetide Prevents Cortical Thinning in Brains of Schizophrenia Patients

Posted: May 26, 2011

Brain and Behavior Research Foundation-Funded Study Provides Explanation for Why People with Schizophrenia Have Difficulty with Social Cues

Posted: April 11, 2011

Leading Researcher Uses Innovative Ways To Improve Treatments

Twenty-year career leading discoveries into the complex circuitry of the brain points toward more effective treatments, foundation-funded discovery of new schizophrenia gene could lead to new diagnostic and therapy possibilities.

Posted: March 23, 2011

NARSAD Investigator Makes Major Breakthrough in Understanding Brain Function

Posted: March 01, 2011

Stem Cells Offer New Insight into Helping the Brain Regenerate

Narsad-funded research breakthrough could improve treatment of schizophrenia.

Posted: February 17, 2011

Upcoming Conference: “Advancing Drug Discovery for Schizophrenia”

Posted: February 07, 2011

Hearing from NARSAD Young Investigators (Part 2)

Posted: February 04, 2011

The NARSAD Feed: NARSAD-Funded Discoveries, Economics of (Mental) Health Care Reform, Meditation and Your Brain

Posted: February 01, 2011

NARSAD Supports Innovative Technologies That Improve Treatment of Mental Illness

Narsad scientific council member discovers key dopamine receptor structure.

Posted: January 03, 2011

NARSAD-Funded Research Suggests Brain Scans Could Predict Onset of Schizophrenia

Posted: December 13, 2010

A very grand vision: “We will discover the causes of mental illnesses so that we can someday develop prevention protocol to keep people from developing these illnesses”

Posted: November 01, 2010

NARSAD-Funded Research Identifies New Gene Candidate for Schizophrenia

Can studies of substance abuse in schizophrenia lead to better medications, leading the way - a brilliant mind in schizophrenia research sees cause for optimism.

Posted: October 01, 2010

NARSAD Researcher Makes Progress Toward His Goal of Prevention of Schizophrenia and Other Mental Illnesses

Posted: September 01, 2010

NARSAD Researcher Makes Discovery in Brain’s Decision-Making Process

Posted: April 10, 2010

Schizophrenia: Is Recovery Possible?

‘retraining the brain’ in patients with schizophrenia.

Posted: April 01, 2010

Mary-Claire King and Judith Rapoport: New Hope From Discovery of Rare Genetic Mutations in Schizophrenia

Aaron beck: reducing schizophrenia’s negative symptoms.

Posted: April 25, 2008

Discovery of Important Genetic Links to Schizophrenia

Posted: November 01, 2003

Identification of Genes Associated with Schizophrenia

Posted: April 01, 1996

Discovery of Novel Gene-Regulating Molecule (Transcription Factor) that Mediates Effects of Stress

Posted: December 01, 1989

Approval of Clozapine to Treat Resistant Schizophrenia

Key figures.

3.5 million adults (1.1%) of the US Adult population live with schizophrenia*

* Source: National Institute of Mental Health

More than 21 million people worldwide are affected by schizophrenia*

* Source: World Health Organization (WHO) 

Featured Tweet

New risk genes for #schizophrenia have been discovered by studying DNA in highly compressed bundles. TWEET

Meet a Researcher

Thomas W. Weickert, Ph.D.

Senior Research Scientist of Neuroscience and Physiology

SUNY Upstate Medical University

2016 Independent Investigator Grant

Ask an Expert

Huda Akil, Ph.D.

Gardner Quarton Distinguished University Professor of Neuroscience and Psychiatry

Co-Director, Molecular and Behavioral Neuroscience Institute

2007 Goldman-Rakic Prize for Outstanding Achievement in Cognitive Neuroscience

In your work with the Pritzker Neuropsychiatric Research Consortium, have you uncovered any new genes that you think might be related to mental illnesses besides major depression?

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Learn More About the Foundation

The Brain & Behavior Research Foundation is a global nonprofit organization focused on improving the understanding, prevention and treatment of psychiatric and mental illnesses.

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Efficacy and effectiveness of antipsychotics in schizophrenia: network meta-analyses combining evidence from randomised controlled trials and real-world data

Affiliations.

• 1 Institute of Primary Health Care, University of Bern, Bern, Switzerland; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Department of Psychiatry, University of Oxford, Oxford, UK.
• 2 Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; School of Pharmacy, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska Institutet, Stockholm, Sweden.
• 3 Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska Institutet, Stockholm, Sweden; Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain; Early Psychosis, Interventions and Clinical Detection Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
• 4 Department of Psychiatry and Psychotherapy, School of Medicine and Health, Technical University of Munich, Munich, Germany.
• 5 Department of Medicine, School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain; Department of Psychiatry, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands; Sant Pau Mental Health Group, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; Department of Clinical Psychiatry, School of Medicine, University of Panama, Panama; Adult Outpatient Clinic, Fundació Pere Mata Terres de l'Ebre, Amposta, Tarragona, Spain.
• 6 Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain.
• 7 Department of Psychiatry and Anatomy & Neurosciences, Amsterdam University Medical Centre, location Vrije Universiteit Amsterdam, Amsterdam, Netherlands; Amsterdam Public Health, Mental Health Program and Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Netherlands; GGZ inGeest Mental Health Care, Amsterdam, Netherlands.
• 8 Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska Institutet, Stockholm, Sweden.
• 9 Sant Pau Mental Health Group, Institut d'Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain; Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain.
• 10 Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Division of Insurance Medicine, Karolinska Institutet, Stockholm, Sweden.
• 11 Early Psychosis, Interventions and Clinical Detection Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; OASIS Service, South London and Maudsley NHS Foundation Trust, London, UK.
• 12 Department of Psychiatry, University of Oxford, Oxford, UK; Oxford Health NHS Foundation Trust, Warneford Hospital, Oxford, UK; Oxford Precision Psychiatry Lab, NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
• 13 Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, University of Barcelona, Barcelona, Catalonia, Spain; Department of Psychiatry and Psychology, Hospital Clinic, Neurosciences Institute, University of Barcelona, Barcelona, Catalonia, Spain.
• 14 Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland; Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Psychiatry Research, Stockholm City Council, Stockholm, Sweden.
• 15 Department of Psychiatry, UMC Utrecht Brain Centre, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands; Amsterdam Public Health, Mental Health Program and Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, Netherlands; GGZ inGeest Mental Health Care, Amsterdam, Netherlands; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University Medical Centre, Maastricht, Netherlands; Outpatient Second Opinion Clinic, GGNet Mental Health, Warnsveld, Netherlands. Electronic address: [email protected].
• PMID: 38215784
• DOI: 10.1016/S2215-0366(23)00366-8

Background: There is debate about the generalisability of results from randomised clinical trials (RCTs) to real-world settings. Studying outcomes of treatments for schizophrenia can shed light on this issue and inform treatment guidelines. We therefore compared the efficacy and effectiveness of antipsychotics for relapse prevention in schizophrenia and estimated overall treatment effects using all available RCT and real-world evidence.

Methods: We conducted network meta-analyses using individual participant data from Swedish and Finnish national registries and aggregate data from RCTs. The target population was adults (age >18 and <65 years) with schizophrenia and schizoaffective disorder with stabilised symptoms. We analysed each registry separately to obtain hazard ratios (HRs) and 95% CIs for relapse within 6 months post-antipsychotic initiation as our main outcome. Interventions studied were antipsychotics, no antipsychotic use, and placebo. We compared HRs versus a reference drug (oral haloperidol) between registries, and between registry individuals who would be eligible and ineligible for RCTs, using the ratio of HRs. We synthesised evidence using network meta-analysis and compared results from our network meta-analysis of real-world data with our network meta-analysis of RCT data, including oral versus long-acting injectable (LAI) formulations. Finally, we conducted a joint real-world and RCT network meta-analysis.

Findings: We included 90 469 individuals from the Swedish and Finnish registries (mean age 45·9 [SD 14·6] years; 43 025 [47·5%] women and 47 467 [52·5%] men, ethnicity data unavailable) and 10 091 individuals from 30 RCTs (mean age 39·6 years [SD 11·7]; 3724 [36·9%] women and 6367 [63·1%] men, 6022 White [59·7%]). We found good agreement in effectiveness of antipsychotics between Swedish and Finnish registries (HR ratio 0·97, 95% CI 0·88-1·08). Drug effectiveness versus no antipsychotic was larger in RCT-eligible than RCT-ineligible individuals (HR ratio 1·40 [1·24-1·59]). Efficacy versus placebo in RCTs was larger than effectiveness versus no antipsychotic in real-world (HR ratio 2·58 [2·02-3·30]). We found no evidence of differences between effectiveness and efficacy for between-drug comparisons (HR ratio vs oral haloperidol 1·17 [0·83-1·65], where HR ratio >1 means superior effectiveness in real-world to RCTs), except for LAI versus oral comparisons (HR ratio 0·73 [0·53-0·99], indicating superior effectiveness in real-world data relative to RCTs). The real-world network meta-analysis showed clozapine was most effective, followed by olanzapine LAI. The RCT network meta-analysis exhibited heterogeneity and inconsistency. The joint real-world and RCT network meta-analysis identified olanzapine as the most efficacious antipsychotic amongst those present in both RCTs and the real world registries.

Interpretation: LAI antipsychotics perform slightly better in the real world than according to RCTs. Otherwise, RCT evidence was in line with real-world evidence for most between-drug comparisons, but RCTs might overestimate effectiveness of antipsychotics observed in routine care settings. Our results further the understanding of the generalisability of RCT findings to clinical practice and can inform preferential prescribing guidelines.

Funding: None.

Copyright © 2024 Elsevier Ltd. All rights reserved.

Publication types

• Meta-Analysis
• Antipsychotic Agents* / therapeutic use
• Benzodiazepines
• Haloperidol / therapeutic use
• Middle Aged
• Network Meta-Analysis
• Olanzapine / therapeutic use
• Randomized Controlled Trials as Topic
• Risperidone
• Schizophrenia* / drug therapy
• Antipsychotic Agents
• Haloperidol

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Research articles

RNA-sequencing suggests extracellular matrix and vasculature dysregulation could impair neurogenesis in schizophrenia cases with elevated inflammation

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Socioeconomic status, personality, and major mental disorders: a bidirectional Mendelian randomization study

Differences in schizophrenia treatments by race and ethnicity—analysis of electronic health records

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Association of cytokines levels, psychopathology and cognition among CR-TRS patients with metabolic syndrome

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Racial disparities with PRN medication usage in inpatient psychiatric treatment

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Variations to plasma H 2 O 2 levels and TAC in chronical medicated and treatment-resistant male schizophrenia patients: Correlations with psychopathology

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Transplantation of gut microbiota derived from patients with schizophrenia induces schizophrenia-like behaviors and dysregulated brain transcript response in mice

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The Ethiopian Cognitive Assessment battery in Schizophrenia (ECAS): a validation study

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Further clarification of cognitive processes of prospective memory in schizophrenia by comparing eye-tracking and ecologically-valid measurements

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Visualizing threat and trustworthiness prior beliefs in face perception in high versus low paranoia

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Mapping the landscape: a bibliometric analysis of resting-state fMRI research on schizophrenia over the past 25 years

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Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia

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Genetic overlap between schizophrenia and cognitive performance

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The relationship between visual hallucinations, functioning, and suicidality over the course of illness: a 10-year follow-up study in first-episode psychosis

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Schizophrenia Research: Latest Findings

Schizophrenia research is ongoing, and new developments are consistently being made. For some people with schizophrenia, findings can introduce new interventions that may significantly affect their lives at critical points, possibly improving schizophrenia symptoms and functioning. 

Researchers suggest that genetic and environmental factors play a role in the development course of schizophrenia and look to examine the ways such factors might be mitigated with interventions. Other research might focus on prevention, brain changes in particular stages of the illness, or psychotic symptoms. 

Schizophrenia research

Considered the official journal of the Schizophrenia International Research Society (SIRS), the Schizophrenia Research journal gathers findings from multiple studies in one place, featuring various clinical trials, systematic reviews, and meta-analyses. 

For example, one recent study focused on the relationship between negative symptoms and motivation toward monetary rewards. The study in question looked at both bipolar disorder and schizophrenia and suggested that negative symptoms were linked with lower motivation for goal-oriented, monetary rewards.

Early psychosis research

A global network of researchers called Accelerating Medicines Partnership Schizophrenia (AMP SCZ), which was launched in 2020, is presently working to study young, at-risk people for schizophrenia .

Mount Sinai has announced that this network of researchers is entering a new phase of testing preventive measures and interventions for addressing schizophrenia symptoms. According to Mount Sinai, "MP SCZ is collecting data on biomarkers that could predict which individuals are at risk for developing psychosis." The participants, who are between 12 and 30, are spread across 13 countries. 

On June 2023, Mount Sinai researchers from around the world presented findings on "new psychosis risk biotypes, cannabidiol as a novel treatment for psychosis, and new clinical interventions for early-stage mental illness."

First episode psychosis

One recent study involving 404 persons aged 15 to 40 years old with non-affective first episode psychosis (FEP) participated in a program called the Recovery After Initial Schizophrenia-Early Treatment Program. The program notes that early intervention services have been shown to improve symptoms and functioning in (FEP), but research hasn't yet examined these services' impact on cognitive functioning. To test their theory, participants were put in either community care (CC) or an early intervention program called NAVIGATE for a period of two years. 

The program's findings suggest that early intervention programs may not be as significant in improving cognitive functioning for older FEP patients but showed effectiveness in improving working memory in younger FEP patients. Participants aged 15 to 19 in the early intervention program indicated significant improvement in working memory. Moreover, improvements in cognitive functioning noted in the first year correlated with reduced symptom severity. The study concluded that "interventions targeting cognition may be required to enhance cognitive functioning in most FEP patients."

Differences in brain structure

A structural and functional MRI study sought to examine progressive changes in the brain throughout the illness course. The study had 115 participants with different stages of schizophrenia, divided according to how long they've had the illness (five, 15, and 25 years). These three groups were matched with a control group of 230 people without schizophrenia or another mental disorder. 

All groups were evaluated using two structural and functional MRI analysis methods, and each group of patients with schizophrenia was compared with the control groups. These methods indicated that brain abnormalities become present at different stages of the illness. The researchers noted that "individual functional abnormalities occur in limited brain areas initially, functional connectivity and gray matter density abnormalities ensue later in wider brain areas, and structural connectivity abnormalities involving almost all white matter tracts emerge in the third decade of the course in schizophrenia."

The study tested the possible effect of long-term usage of antipsychotic medication on the brain. Its findings suggested no "significant correlation" between accumulative exposure to medication and observed brain abnormalities. Currently, brain scans are not considered a reliable method of diagnosis for any mental illness. 

Cognitive symptoms

The cognitive impairment associated with schizophrenia symptoms has been a source of interest for researchers. Current findings suggest that cognitive impairment seems to be distinct from positive and negative symptoms . Using a five-factor model (positive, negative, disorganized, excited, and depressed), the Positive and Negative Syndrome Scale (PANSS) is often used to assess the structure of symptoms. Research indicates the disorganized factor is associated with more cognitive impairment. 

Mental health services

A cross-sectional observational study assessed how diagnosed schizophrenia patients had their first contact with mental health services . The study included 150 schizophrenia patients between 12 and 60 years old. It found that faith healers were the most common "pathway to care," and factors such as family members' education and socioeconomic background influence the choice and perception of psychiatric care. The researchers suggest that "while planning mental health services, emphasis should be made on collaboration between psychiatric and nonpsychiatric services."

Healthcare providers 

A systematic review of the role of primary care physicians in managing schizophrenia in low- and middle-income countries suggests that appropriate training of primary care physicians to address schizophrenia may reduce the treatment gap and introduce interventions for improving quality of life. The review indicates a need for more integrated care of various professionals who encounter individuals at risk for schizophrenia. 

Safeguarding your mental health

Speaking to a therapist may be valuable when struggling with daily life challenges. A therapist can help clients manage stress and find ways to navigate symptoms. If in-person sessions are inconvenient or not easy to access, online therapy can be an accessible way to receive therapy.  

Online therapy through platforms like BetterHelp can be a convenient and easy-to-use option for some people grappling with schizophrenia symptoms across the spectrum. Clients can choose between phone, video, or in-app messaging sessions and access resources like support groups and worksheets. 

A review and synthesis of relevant factors of online psychosocial interventions for psychosis noted that "increased engagement is associated with improved outcomes," but other factors (individual, environmental, and type of intervention) also influence engagement. The synthesized findings suggest that "interventions should be flexible, easy to use , aim to promote motivation, and incorporate some form of support."

Schizophrenia research findings may introduce new interventions that may significantly affect the lives of people with schizophrenia at critical points, improving symptoms and functioning. 

Researchers suggest that genetic and environmental factors play a role in the development course of schizophrenia and look to examine the ways such factors might be mitigated with appropriate interventions. Research may focus on various areas related to schizophrenia, including brain changes in particular stages of the illness, psychotic symptoms, and environmental factors. 

Considered the official journal of the Schizophrenia International Research Society (SIRS), the Schizophrenia Research journal gathers findings from multiple studies into one place — a source for those looking for the latest on schizophrenia-related findings. Schizophrenia research is ongoing, and new developments are on their way. Speaking to a therapist can also be helpful when struggling with challenges that affect your well-being, regardless of your diagnostic status.  

• How To Establish A Schizophrenia Care Plan Following Diagnosis Medically reviewed by Andrea Brant , LMHC
• Schizophrenia Suicide Rate: How To Address Risk Medically reviewed by April Justice , LICSW
• Schizophrenia
• Relationships and Relations

New study into identical twins suggests a possible treatment for people with schizophrenia disorder

Research led by prof. shani stern at the university of haifa unveils genetic discrepancies in schizophrenia discordant monozygotic twins, offering insights for treatment..

Schizophrenia genetics

Transforming the understanding and treatment of mental illnesses.

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Mental Health Matters Podcast: Pathways to Recovery: Psychosis and Schizophrenia

May 9, 2024 • 75th Anniversary

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Episode summary.

Psychosis, a condition marked by a loss of touch with reality, is distressing for those who experience it and their loved ones. If left untreated, psychosis can have serious impacts on people's lives. But the good news is there's hope. In this episode, we talk with Dr. Robert Heinssen, a leader in the development and adoption of coordinated specialty care for treating psychosis. We learn about the signs and symptoms of psychosis, discuss coordinated specialty care, and explore how NIMH research in psychosis and schizophrenia fundamentally changed the health care landscape.

Dr. Heinssen : People may start not so much by hearing voices, but they might hear sounds or their name being called, and they can look around and check and see, "Well, I don't know where that came from." They may become a little bit anxious and attentive of what's going on in their environment, and maybe they start being a little afraid and suspicious that people around them might be observing them or monitoring them in some way. So changes in all of those areas would be some of the early signs that something is amiss.

Dr. Gordon : Psychosis, a condition marked by a loss of touch with reality, is distressing for both those who experience it and their loved ones. If left untreated, psychosis can have serious impacts on people's lives. But the good news is there's hope. Hello, and welcome to Mental Health Matters, a National Institute of Mental Health podcast. I'm Dr. Joshua Gordon, Director of NIMH, and today we'll be talking with Dr. Robert Heinssen, a leader in the development and adoption of coordinated specialty care for treating psychosis. In this episode, we'll learn about the signs and symptoms of psychosis, talk about coordinated specialty care, and discuss how NIMH research in psychosis and schizophrenia fundamentally changed the healthcare landscape. Welcome to Dr. Robert Heinssen of the National Institute of Mental Health. Bob, it's a pleasure to have you here today.

Dr. Heinssen : Dr. Gordon, thank you for this opportunity, and I am equally pleased to be here with you.

Dr. Gordon : Today we're going to talk about psychosis, which is a serious mental condition, of course. Can you talk about what that is exactly?

Dr. Heinssen : Sure. So, psychosis is a condition that affects an individual's perception of reality, their thinking, and their functioning. So to unpack that a little bit, people who are experiencing psychosis may see or hear things that aren't apparent to other individuals. They may have difficulties in their thinking in terms of memory or concentration. Those difficulties may impede their ability to converse with somebody in a fluent way, which has some impact on the person's social relationships, interpersonal relationships. And that can get to be a problem in situations like school and work.

Dr. Gordon : It sounds like it's a real challenge and a burden for those who have it. What causes psychosis?

Dr. Heinssen : Well, there are a variety of pathways to psychosis. You could have a medical condition or an acute infection, a fever that would, in some cases, cause some of these symptoms. Sometimes abuse of substances or alcohol can cause psychotic symptoms. And there are some conditions that are independent of those causes that are mental disorders that start usually in late adolescence and, if untreated, can progress into the person's young adult and adult life.

Dr. Gordon : One of the mental illnesses we often think of as associated with psychosis is schizophrenia. Can you talk about the relationship between psychosis in general and schizophrenia specifically?

Dr. Heinssen : Sure. So, schizophrenia is a very disabling condition, but it includes among the symptoms of that condition, psychosis is a central feature. To make a diagnosis of schizophrenia, professionals require a period of time where psychotic symptoms are present before they'll make the determination that it's clearly schizophrenia. So, for a young person, some of those cognitive problems and perceptual problems might become a barrier to them functioning effectively in a school situation. The anxiety and distress that they feel may cause them to withdraw from other people around them, their friends, other students, even their family members. And that would create the social difficulty and isolation that is often seen later in schizophrenia. And again, without intervention, this can spiral into a set of symptoms and then functional problems that really impede the person's ability to achieve expected developmental milestones of education, relationships, work, and so forth.

Dr. Gordon : So psychosis, and in particular the psychosis that accompanies schizophrenia can be devastating. It can really prevent people from being able to lead normal lives.

Dr. Heinssen : I think devastating is the right word. It's devastating for the individual who is experiencing these symptoms. It's devastating to family members who observe changes and often are unsure of what is driving those changes.

Dr. Gordon : What's one thing you'd want people to understand about psychosis?

Dr. Heinssen : One thing I'd want people to understand is that behind the symptoms are human beings that have hopes and dreams and aspirations just like the rest of us. The symptoms sometimes create a barrier between the person with psychosis and others. If you look behind those symptoms, you see the promise of a human being, of an individual who wants the same things that you want out of life and has the same aspirations, the same type of goals, and the same type of prospects. So if we look beyond the symptoms to the human being, we'll perhaps have more compassion to offer this kind of assistance that help people get to the kind of futures that we all want.

Dr. Gordon : Can people recover from a psychotic episode? Can people get better?

Dr. Heinssen : So, Josh, a little bit of history here. If you asked me that question in 1990, I, like most mental health professionals, would say, "Well, people will get better with treatment. Their chances for full recovery are probably slight." And that was the message that healthcare professionals delivered in the late 1980s, early 1990s. But through research that has identified a critical period for intervention in the early stages of psychosis, we now have a very different story, a much more optimistic story that early intervention can really help people gain control of these symptoms, to get back on track with things like school and relationships and work. And with enduring care, over time, they can expect to lead productive, fulfilling, and meaningful life. So yes. Short answer, yes, recovery is possible.

Dr. Gordon : Tell me about ways that we might be able to help people recognize that something is wrong.

Dr. Heinssen : It's not always clear that something that it's a start of an illness or a disorder, it could just be people might say the child is going through a phase or having a rough spot, but educating the individuals who are experiencing the condition, the parents or caregivers who were surrounding them, the health care providers that would be the first professionals to come in contact and then mobilizing our healthcare system so that there are open doors when individuals present for a consultation and potential care that they have rapid access to those services, that the services can rapidly perform an evaluation and then, when indicated, can rapidly start the treatment. All of those things reduce the interval between the onset of symptoms and the initiation of treatment. And we know from NIMH-supported research that intervals, often called the duration of untreated psychosis, is an important factor in determining how well people will respond to treatment and to what extent they will recover in the long term.

Dr. Gordon : So it's important to detect risk for psychosis early because getting people into treatment early means that they can have better outcomes.

Dr. Heinssen : Yes, time is our enemy. The faster we can identify and intervene, the much more potent are our existing interventions.

Dr. Gordon : Let's say someone does have psychosis. They have schizophrenia, so not necessarily the first episode. What's the role of medication and other forms of treatment for individuals with psychosis?

Dr. Heinssen : We do have individual treatments that do help with components of the experience of psychosis. So antipsychotic medications are an effective strategy for dealing with some of the perceptual problems, the hallucinations that people might be seeing or hearing things that others don't see. They are all also affected with some of the distortions and thinking, some of these ideas that others are monitoring them, there are suspiciousness or worries in that regard. Antipsychotic medications can help with that component of psychosis. Psychotherapies, particularly cognitive and behavioral psychotherapies, are a very effective way of dealing with the distress that people feel and for managing the disruption that has occurred in their lives.

The cognitive and behavioral therapies can help the person, one, come to terms with the experience that they're having. It can reinstill an optimism that recovery is possible and it can help them map out a treatment plan that will set out a roadmap and goals for resuming their normal activities. In addition to that, we know that family education and support is very crucial in helping the family be a support to the individual and help them as they negotiate or navigate their recovery from these episodes.

Dr. Gordon : An important effort in understanding how best to care for these young people who are experiencing their first episode of psychosis was funded by NIMH. The recovery after an initial schizophrenia episode or RAISE Study. What were the main findings? What was involved in getting that off the ground?

Dr. Heinssen : So, a little historical context. By the late 1990s, researchers throughout the world were actually recognizing this idea that early intervention in this critical window could make a real difference. It could help people recover from their initial episode of psychosis and could put them onto a path of more normal functioning. So there were a number of research studies that were exploring how this could be done, and in those, they were testing various models that had these multiple components to address the various symptoms of psychosis. So a number of us at NIMH were looking at these results and thinking, if this could work in the United States, this really could be a very big advance for young people with psychosis and their families.

So three research aims, feasibility, effectiveness, and scalability, were at the heart of the recovery after an initial schizophrenia episode initiative. And NIMH launched that in 2008 and we ended up funding two studies. One of them was a comparative effectiveness study. This took place in 34 community clinics throughout the United States. And 17 of these clinic programs were assigned to that type of coordinated treatment. And then the remaining 17 clinics provided treatment as usual. That study addressed the questions of feasibility and effectiveness. And then a second study, an implementation study, explored what would be potential barriers to implementing such a coordinated approach in public health settings across the U.S.

And that study identified barriers, but more importantly, they developed approaches to be able to surmount those barriers and make it possible that this intervention would be able to be delivered with fidelity and to be done on a broad scale. We had stunning success in both studies. Coordinated treatment was more effective than treatment as usual in terms of improving quality of life and reducing distressing symptoms, and helping individuals return to school and work. These programs led to the adoption of coordinated specialty care by the states of New York and Maryland immediately after the research was concluded. So those two studies set a foundation for a broad implementation of this new approach across the United States.

Dr. Gordon : Can you talk about what effect the RAISE Study has had on mental health care, in particular for health care for first-episode psychosis in the U.S.?

Dr. Heinssen : Sure. I'll start this by saying that NIMH science has been a very critical element in this success story. But it's one element and one thing that I learned is as terrific as our science is, if we don't have partnerships with key stakeholders, it's not a given that science will actually make its way into the healthcare system. So in this case, we did this study in the context of growing awareness among federal partners, among advocacy groups, among private foundations, that early intervention was really a new concept that should be exploited.

And we worked very hard with all of those stakeholders to be able to translate the science into new clinical practice. And hats off to our partners at the Substance Abuse and Mental Health Services Administration who embraced this new scientific approach and partnered with us in disseminating the new approaches, in training people in being able to implement them, and then providing the resources or channeling the resources that Congress provided through their community mental health block grant to fund these new programs, these coordinated specialty care programs via a set aside to their block grant program.

So all of this came together, the science, the partnerships, and the coordinated effort to move the science into practice. And today, it's a much different world. In 2008, we know that there were only two states that had committed to early intervention as a state policy in mental health care. And we estimate that there were only about a dozen high-quality specialty care programs in the United States at that time. A dozen years later, there are over 350 of these programs in all 50 states, and they today serve tens of thousands of young people each year.

Dr. Gordon : Can you compare what treatment and prognosis is like for individuals experiencing their first episode of psychosis before and after RAISE?

Dr. Heinssen : So if we look back in the United States in the late 1990s and early 2000s, in academic circles, there was recognition that early intervention was the way to go, and people were studying ways to do that, but that message had not gone to the broader community. So if you were somebody experienced a first episode psychosis, in all likelihood, your symptoms would really not be recognized until some sort of crisis occurred that required either an emergency department visit or an unplanned inpatient treatment, or in some cases, contact with the police that might result in arrest and involuntary commitment to one of these treatment facilities.

Once you got into treatment, the chances were that you were going to be evaluated and treated by somebody who didn't have a wealth of experience in early psychosis. So your care would likely be fragmented. It may not have been up to the guidelines that existed for medication treatment at that point, and it would not have been continuous. You would have been discharged from an inpatient facility and left on your own, perhaps with the help of your family, to try to navigate outpatient services. Now, today, the best-case scenario is very different. In these programs that have established referral networks in the community, very often, a person can be referred to a first-episode psychosis program before an initial hospitalization. So the differences are really kind of night and day, and the outcomes are also night and day.

Dr. Gordon : Early intervention is key. Before RAISE, before these clinics, did people have to wait a long time for care in order to get it?

Dr. Heinssen : Yeah. In the United States, believe it or not, a person could be psychotic for anywhere between one and three years.

Dr. Gordon : Years?

Dr. Heinssen : Years.

Dr. Gordon : Wow.

Dr. Heinssen : In the RAISE program, the average amount of time a person waited was 18 months. And think about that. Psychotic symptoms, they're very dramatic, and they're very disabling, and they are associated with a lot of distress and pain. And for people experiencing those symptoms for that period of time, it's just astounding that was the state of care.

Dr. Gordon : So RAISE showed us that we can reduce the time to treat psychosis, and we can get people better and keep them better if we get them into a coordinated specialty care treatment and ensure continuity of care. What has NIMH been up to try to solidify that success of RAISE, to make sure that we're doing the best we can to treat individuals in their first episode of psychosis?

Dr. Heinssen : So the results of the RAISE study, the principal results started to become available around 2014, 2015. I think at that point there were maybe somewhere around 50 or 60 of these programs nationwide. So we started thinking there's 50 or 60 of these programs, and it would be great if we had 50 excellent programs in the United States. But imagine what would happen if you linked those programs together so that they could talk to one another, they could share data, they could share learning. So that became the beginning of an idea that we imagined, an Early Psychosis Intervention Network, or EPINET. And the idea started in 2015. And then we took some lessons learned from the RAISE program in developing that idea. We started funding regional networks in 2019.

So this would be a network of like-minded programs that offered services within a defined area. And then we have linked those regional networks through a national data coordinating center. And so together, this enterprise embraces 8 regional networks, 101 community clinics throughout the United States, well, in 17 states. And we're anticipating that somewhere between 3,000 and 4,000 young people with first-episode psychosis will be enrolled in these programs.

Dr. Gordon : Wow. So 100 clinics, thousands of individuals, all participating in an effort to really understand how best to take care of people with first-episode psychosis, what are they learning?

Dr. Heinssen : I like to think of this. If you're a person with cancer and you go to a cancer clinic that's affiliated with a research program, you go in there and you know that information about your care is going to be utilized by that clinic to help them improve the quality of the care that they offer and then also to offer you opportunities to participate in research that may benefit others by generating increased knowledge about cancer and its treatment. We're building that same kind of culture within the EPINET clinics that people come in there and they're first struck with this idea that this is a different experience. The person who's entering this program will know that I'm in a program that looks at its procedures continuously with an eye towards improvement. That's the kind of system that a person will be entering in.

Dr. Gordon : So these learning health care systems, these clinics, they're not just providing care, they're asking the questions that will help them provide better care in the future. Bob, what's it like for a patient who's in one of these first episode psychosis clinics, from their point of view, what are they getting?

Dr. Heinssen : So they're getting access to a treatment team. So it all starts with conversations about what's happened and what's been disrupted for you. What would you like to return to or what would you like to get out of treatment? And then here are some of the tools that we have that we can make available to you. And then that conversation with the treatment team leads to an individualized treatment plan that usually is a combination of the medication, the psychotherapy, the family intervention, and these rehabilitation or supported employment and education activities. Then the interesting thing, what I hear from people who run these programs, young people are interested in getting back on track with their lives. And they embrace this as their job. Their job is to get better and get back on track.

Dr. Gordon : So how long will a person stay in one of these first-episode psychosis clinics? How long will they be in a program like that?

Dr. Heinssen : I would say between one and three years is probably typical. Most programs organize themselves around two years. Important to note that the treatment plans are individualized. So this is not like you're going through a program and that you have the same program over the course of a year or two years. You have an individualized treatment plan, and that plan adjusts continuously based on your recovery, your emerging needs, and so forth.

Dr. Gordon : What inspires you as a scientist?

Dr. Heinssen : So before I came to NIMH, I worked in a psychiatric hospital that was the center of a community treatment program for serious mental illness, for schizophrenia. And I ran a treatment program for adults with serious mental illness, several hundred adults. And these programs, I thought they were quite good in embracing a lot of the science-based treatments that were available at that time. I was very proud of the fact that we were able to move people out of hospital settings into the community and to help them lead independent lives in the community. One day, I was giving a talk about this treatment program and what was available to people with serious mental illness, and I gave the talk. I was very proud to talk about our programs, about how they were science-based, the outcomes we had achieved. And I was feeling very good about this meeting. There was a long line of people who wanted to speak with me afterwards.

The last person was somebody who looked very familiar to me. The woman introduced herself and she said, " Dr. Heinssen , you might remember me. My son so-and-so was in your program." I immediately remembered who she was talking about, and I was thinking, "Boy, this is going to be great. He did so well." He was a young man who had had schizophrenia for several years by the time he came into our program. But we had helped him to achieve his goal of returning to college. He was going to community college. He was taking a course. He was living in an assisted living facility, but he was living in the community. And he was also working part-time in a grocery store. And I thought this was a great...this is a great outcome. And I was waiting for this feedback, boy, what a great outcome. And the woman started crying and she said, "I know I should be grateful, he's doing so much better than he was but we had hoped for so much more."

And that really arrested me thinking that on the one hand, we did the best that we could do given the current state of knowledge, but hubris was not called for in this situation. Humility was called for. I had the opportunity to come to NIMH very shortly after that, and when I had the opportunity to jump on to this early intervention research, that mother's story was in the back of my mind. Her voice was ringing in my ears that we had hoped for so much more. And I thought, "There's so much more that we need to do." That was the initial impetus and that's been the thing that has kept me in the race for as long as I have been, that it is only through research and then through the hard work of implementing the research that we can hope for better outcomes. That really has been the motivation for me over these 22 years. So to that woman, if you hear this podcast, thank you very much. You changed the whole trajectory of my career.

Dr. Gordon : This concludes this episode of Mental Health Matters. I'd like to thank our guest, Dr. Robert Heinssen, for joining us today. And I'd like to thank you for listening. If you enjoyed this podcast, please subscribe and tell a friend to tune in. If you'd like to know more about psychosis or coordinated specialty care, please visit nimh.gov. We hope you'll join us for the next podcast.

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Reporting by Puyaan Singh in Bengaluru; Editing by Devika Syamnath

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