Robust Brain Correlates of Cognitive Performance in Psychosis and Its Prodrome

• Published in: Biological psychiatry (1969) 2025-01, Vol.97 (2), p.139-147
• Main Authors: Ward, Heather Burrell, Beermann, Adam, Xie, Jing, Yildiz, Gulcan, Felix, Karlos Manzanarez, Addington, Jean, Bearden, Carrie E., Cadenhead, Kristin, Cannon, Tyrone D., Cornblatt, Barbara, Keshavan, Matcheri, Mathalon, Daniel, Perkins, Diana O., Seidman, Larry, Stone, William S., Tsuang, Ming T., Walker, Elaine F., Woods, Scott, Coleman, Michael J., Bouix, Sylvain, Holt, Daphne J., Öngür, Dost, Breier, Alan, Shenton, Martha E., Heckers, Stephan, Halko, Mark A., Lewandowski, Kathryn E., Brady, Roscoe O.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Auditory; Brain - diagnostic imaging; Brain - physiopathology; Clinical high risk; Cognition - physiology; Cognitive Dysfunction - diagnostic imaging; Cognitive Dysfunction - etiology; Cognitive Dysfunction - physiopathology; Cognitive performance; Connectome; Early psychosis; Female; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prodromal Symptoms; Psychosis; Psychotic Disorders - diagnostic imaging; Psychotic Disorders - physiopathology; Resting-state fMRI; Young Adult
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2024.07.012

Neurocognitive impairment is a well-known phenomenon in schizophrenia that begins prior to psychosis onset. Connectome-wide association studies have inconsistently linked cognitive performance to resting-state functional magnetic resonance imaging. We hypothesized that a carefully selected cognitive instrument and refined population would allow identification of reliable brain-behavior associations with connectome-wide association studies. To test this hypothesis, we first identified brain-cognition correlations via a connectome-wide association study in early psychosis. We then asked, in an independent dataset, if these brain-cognition relationships would generalize to individuals who develop psychosis in the future. The Seidman Auditory Continuous Performance Task (ACPT) effectively differentiates healthy participants from those with psychosis. Our connectome-wide association study used the HCP-EP (Human Connectome Project for Early Psychosis) (n = 183) to identify links between connectivity and ACPT performance. We then analyzed data from the NAPLS2 (North American Prodrome Longitudinal Study 2) (n = 345), a multisite prospective study of individuals at risk for psychosis. We tested the connectome-wide association study–identified cognition-connectivity relationship in both individuals at risk for psychosis and control participants. Our connectome-wide association study in early-course psychosis identified robust associations between better ACPT performance and higher prefrontal-somatomotor connectivity (p < .005). Prefrontal-somatomotor connectivity was also related to ACPT performance in at-risk individuals who would develop psychosis (n = 17). This finding was not observed in nonconverters (n = 196) or control participants (n = 132). This connectome-wide association study identified reproducible links between connectivity and cognition in separate samples of individuals with psychosis and at-risk individuals who would later develop psychosis. A carefully selected task and population improves the ability of connectome-wide association studies to identify reliable brain-phenotype relationships.