Right caudate deactivation during reward anticipation predicts elevated risk for psychosis in adolescents

Background: Schizophrenia is associated with abnormalities in neurodevelopmental processes. Furthermore, dysfunctional neural circuits involved in reward processing may be linked to the development of symptoms in schizophrenia and are predictive of long-term functional outcome. It is however unknown whether neural signatures of reward processing are detectable in children with an increased risk of psychosis and/or predictive of their prodromal psychosis score. Methods: Using data from the ABCD study 4.1, we defined a healthy control (N=50) and a risk for psychosis (N=50) group with a Prodromal Psychosis Syndrome (PPS) score>3 at baseline (9-10 years) and 2nd-year-follow-up (11-12 years). While undergoing functional MR-imaging, all children completed the Monetary Incentive Delay task. Using the preprocessed ABCD-data, we explore whether behaviour and brain activations for reward and loss anticipation in areas underlying reward processing differed between groups and time-points. Furthermore, we investigated whether those brain activations that showed differences between the groups were predictive of later PPS scores. Results: While behavioural results did not differ, we found that at-risk children demonstrated lower activation during reward anticipation in the caudate for both timepoints, and the nucleus accumbens, the putamen, the dorsolateral and the ventral medial prefrontal cortex for the 2nd-year-follow-up compared to controls. Regression analysis revealed that right caudate deactivation for both timepoints was predictive of later PPS scores. Conclusion: This study reveals that neural alterations during reward anticipation are detectable in children at-risk of psychosis. These dysfunctions in neural activation patterns may serve as a potential predictive biomarker for psychosis.