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 control participants, with nonaffected relatives in between. We also expected negative associations of VS activation with polygenic risk scores (PRSs) and with depressive and negative psychotic symptoms.

One hundred twenty-seven patients, 66 control participants, and 51 first-degree relatives completed the monetary incentive delay task during functional magnetic resonance imaging. Diagnoses were confirmed with clinical interviewing, and PRSs for 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, control participants), 2) effects of manic, depressive, and positive and negative psychotic symptoms (accounting for group for depressive symptoms), and 3) effects of PRSs.

Groups did not differ significantly in VS activation during reward anticipation. Current symptom levels were not significantly related to VS activation, nor was there an interaction with group. PRSs 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.