title: Fronto-striatal dysfunction during reward processing in unaffected siblings of schizophrenia patients.
abstract: Schizophrenia is a psychiatric disorder that is associated with impaired functioning of the fronto-striatal network, in particular during reward processing. However, it is unclear whether this dysfunction is related to the illness itself or whether it reflects a genetic vulnerability to develop schizophrenia. Here, we examined reward processing 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 correlated with sub-clinical negative symptoms. During the outcome of reward, siblings showed increased activation in the ventral striatum and orbitofrontal cortex compared to controls. Our finding of decreased activity in the ventral striatum 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 schizophrenia. 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.
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands mleeuw5@umcutrecht.nl.
authors.forename: Max
authors.initials: M
authors.lastname: de Leeuw
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Vink
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000503:physiopathology; D003463:Cues; D005260:Female; D005625:Frontal Lobe / Q000503:physiopathology*; D059907:Functional Neuroimaging; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009044:Motor Cortex / Q000503:physiopathology*; D017072:Neostriatum / Q000503:physiopathology; D012201:Reward; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D035781:Siblings; D066328:Ventral Striatum / Q000503:physiopathology*
keywords: cue processing; genetic vulnerability; monetary incentive delay task; orbitofrontal cortex; ventral striatum; ventromedial prefrontal cortex