Fronto-striatal Dysfunction During Reward Processing in Unaffected Siblings of Schizophrenia Patients

Schizophrenia is a psychiatric disorder that is associ-ated with impaired functioning of the fronto-striatal net-work, in particular during reward processing. However, it is unclear whether this dysfunction is related to the ill-ness itself or whether it reflects a genetic vulnerability to develop schizophrenia. Here, we examined reward process-ing in unaffected siblings of schizophrenia patients using functional magnetic resonance imaging. Brain activity was measured during reward anticipation and reward outcome in 27 unaffected siblings of schizophrenia patients and 29 healthy volunteers using a modified monetary incentive delay task. Task performance was manipulated online so that all subjects won the same amount of money. Despite equal performance, siblings showed reduced activation in the ventral striatum, insula, and supplementary motor area (SMA) during reward anticipation compared to controls. Decreased ventral striatal activation in siblings was corre-lated with sub-clinical negative symptoms. During the out-come of reward, siblings showed increased activation in the ventral striatum and orbitofrontal cortex compared to con-trols. Our finding of decreased activity in the ventral stria-tum during reward anticipation and increased activity in this region during receiving reward may indicate impaired cue processing in siblings. This is consistent with the notion of dopamine dysfunction typically associated with schizo-phrenia. Since unaffected siblings share on average 50% of their genes with their ill relatives, these deficits may be related to the genetic vulnerability for schizophrenia