Reward Processing as an Indicator of Vulnerability or Compensatory Resilience in Psychoses? Results From a Twin Study

Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where one twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this. We used Danish registries to identify twin pairs with at least one twin having a schizophrenia spectrum disorder diagnosis and control twin pairs matched on age, sex and zygosity. The analyses include data from 34 unaffected co-twins (16 females), 42 probands with schizophrenia spectrum disorder (17 females), and 83 control twins (42 females). Participants performed a modified incentive delay task during functional magnetic resonance imaging. Whole-brain group differences were analyzed by performing comparisons between co-twins and control twins. Correlations with cognitive flexibility were tested. Compared to control twins, co-twins showed no differences in striatal regions, but increased signal in the dorsolateral prefrontal cortex (DLPFC) during missed target contrast was observed. In co-twins, increased DLPFC signal was associated with lower intra-extra dimensional set-shifting scores indicative of higher cognitive flexibility. The unaffected co-twins did not have decreased striatal activity during anticipation as previously reported for patients with schizophrenia. Instead, they showed increased activity in DLPFC during evaluation of missed target contrast, which correlated with their level of cognitive flexibility. Importantly, the unaffected co-twins had no diagnosis at a mean age of 40. This could indicate that greater cognitive flexibility and increased activity in the right DLPFC during processing of unexpected negative outcome represents a compensatory resilience mechanism in the predisposed twins.