Neural correlates of reward processing in healthy siblings of patients with schizophrenia

Esther Hanssen, Jorien van der Velde, Paula M. Gromann, Sukhi S. Shergill, Lieuwe de Haan, Richard Bruggeman, Lydia Krabbendam, André Aleman, Nienke van Atteveldt

Deficits in motivational behavior and psychotic symptoms often observed in schizophrenia (SZ) may be driven by dysfunctional reward processing (RP). RP can be divided in two different stages; reward anticipation and reward consumption. Aberrant processing during reward anticipation seems to be related to SZ. Studies in patients with SZ have found less activation in the ventral striatum (VS) during anticipation of reward, but these findings do not provide information on effect of the genetic load on reward processing. Therefore, this study investigated RP in healthy first-degree relatives of SZ patients. The sample consisted of 94 healthy siblings of SZ patients and 57 healthy controls. Participants completed a classic RP task, the Monetary Incentive Delay task, during functional magnetic resonance imaging (fMRI). As expected, there were no behavioral differences between groups. In contrast to our expectations, we found no differences in any of the anticipatory reward related brain areas (region of interest analyses). Whole-brain analyses did reveal group differences during both reward anticipation and reward consumption; during reward anticipation siblings showed less deactivation in the insula, posterior cingulate cortex (PCC) and medial frontal gyrus (MFG) than controls. During reward consumption siblings showed less deactivation in the PCC and the right MFG compared to controls and activation in contrast to deactivation in controls in the precuneus and the left MFG. Exclusively in siblings, MFG activity correlated positively with subclinical negative symptoms. These regions are typically associated with the default mode network (DMN), which normally shows decreases in activation during task-related cognitive processes. Thus, in contrast to prior literature in patients with SZ, the results do not point to altered brain activity in classical RP brain areas, such as the VS. However, the weaker deactivation found outside the reward-related network in siblings could indicate reduced task-related suppression (i.e., hyperactivation) of the DMN. The presence of DMN hyperactivation during reward anticipation and reward consumption might indicate that siblings of patients with SZ have a higher baseline level of DMN activation and possible abnormal network functioning.