Groundbreaking Study Shows Promise for Early Detection and Intervention in Psychotic Disorders Such As Schizophrenia

According to new research, cognitive impairments in psychotic disorders, such as schizophrenia and bipolar disorder, are linked to brain network organization. This link between cognition and brain networks is present in individuals considered at-risk for psychotic disorders even prior to their first psychotic break. This groundbreaking study opens in new tab/window in Biological Psychiatry opens in new tab/window, published by Elsevier, suggests an opportunity for early diagnosis and intervention for these treatment-resistant symptoms.

Lead author Heather Burrell Ward, MD, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, explains, "Cognitive impairment is highly prevalent in schizophrenia and other psychotic disorders. There are currently no medications to treat cognitive impairment, resulting in significant disability. This impairment is frequently present by the time an individual has their first psychotic break, making early detection and intervention critical. Our current study is part of our work to understand and treat the medication-resistant symptoms of psychotic disorders."

Several cognitive domains found to be reliably impaired in psychotic disorders have received intensive study, such as overall cognitive ability. To measure cognitive impairment in psychosis, most studies have utilized cognitive tasks originally designed and validated in control populations. However, these studies do not address the question of whether cognitive constructs map onto quantifiable brain substrates. The current research used a cutting-edge MRI analysis approach and a cognitive test designed for people with psychosis to analyze data collected by two consortia of researchers: the Human Connectome Project for Early Psychosis (HCP-EP) and the North American Prodrome Longitudinal Study (NAPLS).

Co-senior author Roscoe O. Brady, Jr., MD, PhD, Harvard Medical School; Department of Psychiatry, Beth Israel Deaconess Medical Center, and McLean Hospital and Harvard Medical School, notes, "We observed that in individuals with psychotic disorders, cognitive impairment is linked to brain network organization. We then attempted something that has not been previously demonstrated: We asked if we can observe this same brain signature of cognitive impairment in individuals prior to their psychotic break. We analyzed data from individuals considered at-risk for psychotic disorders, but who had not yet had their first psychotic episode. We identified this same brain network-cognition relationship only in individuals who would eventually develop psychosis in the future."

Commenting on the implications of the study, John Krystal, MD, Editor of Biological Psychiatry, says, "Researchers of this novel study used the combination of a data-driven connectome-wide multivariate pattern analysis and a disease-informed cognitive assessment to identify a novel and reproducible relationship between brain connectivity and cognitive performance in psychotic disorders, offering important insights for the early detection and intervention of psychotic disorders."

Co-senior author Kathryn E. Lewandowski, PhD, McLean Hospital and Harvard Medical School, concludes, "There is an ongoing international effort to identify biomarkers and targets for intervention in individuals at-risk for psychotic disorders through the Accelerating Medicines Partnership^® Schizophrenia (AMP SCZ). Our discovery of a link between cognition and brain networks, observed even prior to the first psychotic break, suggests an opportunity for early diagnosis and intervention, such as via noninvasive neuromodulation."

Notes for editors

The article is "Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome," by Heather Burrell Ward, MD, Adam Beermann, MA, Jing Xie, BA, Gulcan Yildiz, MD, Karlos Manzanarez Felix, BS, Jean Addington, PhD, Carrie E. Bearden, PhD, Kristin Cadenhead, MD, Tyrone D. Cannon, PhD, Barbara Cornblatt, PhD, MBA, Matcheri Keshavan, MD, Daniel Mathalon, MD, PhD, Diana O. Perkins, MD, MPH, Larry Seidman, PhD, William S. Stone, PhD, Ming T. Tsuang, MD, PhD, DSc, Elaine F. Walker, PhD, Scott Woods, MD, Michael J. Coleman, MA, Sylvain Bouix, PhD, Daphne J. Holt, MD, PhD, Dost Öngür, MD, PhD, Alan Breier, MD, Martha E. Shenton, PhD, Stephan Heckers, MD, Mark A. Halko, PhD, Kathryn E. Lewandowski, PhD, and Roscoe O. Brady, Jr., MD, PhD (https://doi.org/10.1016/j.biopsych.2024.07.012 opens in new tab/window). It appears online in Biological Psychiatry, published by Elsevier.

The article is openly available at https://www.biologicalpsychiatryjournal.com/article/S0006-3223(24)01460-4/fulltext opens in new tab/window.

Copies of this paper and additional information are also available to credentialed journalists upon request; please contact Rhiannon Bugno at [email protected] opens in new tab/window. Journalists wishing to interview the authors should contact:

For Heather Ward, MD: contact Craig Boerner at +1 615 322 4747 or [email protected] opens in new tab/window

For Roscoe Brady, MD, PhD: contact Katie Brace at +1 617 667 7300 or [email protected] opens in new tab/window

For Kathryn E. Lewandowski, PhD: email Ryan Jaslow at [email protected] opens in new tab/window or Tim Sullivan at [email protected] opens in new tab/window

This work was supported by the Sidney R. Baer, Jr. Foundation and Harvard Medical School Department of Psychiatry Norman E. Zinberg Fellowship in Addiction Psychiatry Research, and National Institutes of Health (NIH) grants K23DA059690, KL2TR002245, U01 MH066134, P50 MH066286, 1R01MH120588-01A1, U01 MH081902, U01 MH081857, R01 MH117012, U01 MH109977, U01 MH82022, U01 MH081944, U01 MH066069, R01 MH076989, U01 MH081928, U01 MH081988, and R01 MH116170.

The authors’ affiliations and disclosures of financial and conflicts of interests are available in the article.

John H. Krystal, MD, is Chairman of the Department of Psychiatry at the Yale University School of Medicine, Chief of Psychiatry at Yale-New Haven Hospital, and a research psychiatrist at the VA Connecticut Healthcare System. His disclosures of financial and conflicts of interests are available here opens in new tab/window.

About Biological Psychiatry

Biological Psychiatry opens in new tab/window is the official journal of the Society of Biological Psychiatry opens in new tab/window, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms, and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

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