- Ward, Heather;
- Beermann, Adam;
- Xie, Jing;
- Yildiz, Gulcan;
- Felix, Karlos;
- Addington, Jean;
- Bearden, Carrie;
- Cadenhead, Kristin;
- Cannon, Tyrone;
- Cornblatt, Barbara;
- Keshavan, Matcheri;
- Mathalon, Daniel;
- Perkins, Diana;
- Seidman, Larry;
- Stone, William;
- Tsuang, Ming;
- Walker, Elaine;
- Woods, Scott;
- Coleman, Michael;
- Bouix, Sylvain;
- Holt, Daphne;
- Öngür, Dost;
- Breier, Alan;
- Shenton, Martha;
- Heckers, Stephan;
- Halko, Mark;
- Lewandowski, Kathryn;
- Brady, Roscoe
BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.