Reward-Related Brain Function as an Endophenotype in the Mood-Psychosis Spectrum

Function of the striatal reward system has been implicated in both psychotic and bipolar disorders. We aimed to test whether ventral striatum (VS) activation during reward anticipation meets criteria of an endophenotype of these disorders. We hypothesized VS activation to be lower in patients than controls, with non-affected relatives in between. We also expected negative associations of VS activation with polygenic risk scores and with depressive and negative psychotic symptoms. 127 patients, 66 controls and 51 first-degree relatives completed the monetary incentive delay task during fMRI. Diagnoses were confirmed with clinical interviewing, and polygenic risk scores of schizophrenia, bipolar disorder and major depressive disorder were calculated from DNA-testing of whole blood. Neural activation in the VS during reward anticipation was the main outcome. Linear mixed effects models tested 1) group differences (patients, relatives, controls), and effects of 2) manic, depressive, and positive and negative psychotic symptoms (accounting for group for depressive symptoms), and 3) polygenic risk scores. Groups did not differ significantly in VS activation during reward anticipation. Current symptom levels were not significantly related to VS activation, also not in interaction with group. Polygenic risk scores were not significantly associated with VS activation. Findings were consistent after controlling for substance use and medication use. We did not find evidence that VS activation during reward anticipation meets criteria of an endophenotype of bipolar and psychotic disorders. Future research should examine associations between neural activation and symptom levels across diagnostic boundaries in a more symptomatic sample.