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.

Inhibitory control, like most cognitive processes, is subject to an age-related decline. The effect of age on neurofunctional inhibition processing remains uncertain, with age-related increases as well as decreases in activation being reported. This is possibly because reactive (i.e., outright stopping) and proactive inhibition (i.e., anticipation of stopping) have not been evaluated separately. Here, we investigate the effects of aging on reactive as well as proactive inhibition, using functional MRI in 73 healthy subjects aged 30-70years. We found reactive inhibition to slow down with advancing age, which was paralleled by increased activation in the motor cortex. Behaviorally, older adults did not exercise increased proactive inhibition strategies compared to younger adults. However, the pattern of activation in the right inferior frontal gyrus (rIFG) showed a clear age-effect on proactive inhibition: rather than flexibly engaging the rIFG in response to varying stop-signal probabilities, older subjects showed an overall hyperactivation. Whole-brain analyses revealed similar hyperactivations in various other frontal and parietal brain regions. These results are in line with the neural compensation hypothesis of aging: processing becomes less flexible and efficient with advancing age, which is compensated for by overall enhanced activation. Moreover, by disentangling reactive and proactive inhibition, we can show for the first time that the age-related increase in activation during inhibition that is reported generally by prior studies may be the result of compensation for reduced neural flexibility related to proactive control strategies.

A recent Genome-Wide Association Study showed that the rs2514218 single nucleotide polymorphism (SNP) in close proximity to dopamine receptor D2 is strongly associated with schizophrenia. Further, an in silico experiment showed that rs2514218 has a cis expression quantitative trait locus effect in the basal ganglia. To date, however, the functional consequence of this SNP is unknown. Here, we used functional Magnetic resonance imaging to investigate the impact of this risk allele on striatal activation during proactive and reactive response inhibition in 45 unaffected siblings of schizophrenia patients. We included siblings to circumvent the illness specific confounds affecting striatal functioning independent from gene effects. Behavioral analyses revealed no differences between the carriers (n = 21) and noncarriers (n = 24). Risk allele carriers showed a diminished striatal response to increasing proactive inhibitory control demands, whereas overall level of striatal activation in carriers was elevated compared to noncarriers. Finally, risk allele carriers showed a blunted striatal response during successful reactive inhibition compared to the noncarriers. These data are consistent with earlier reports showing similar deficits in schizophrenia patients, and point to a failure to flexibly engage the striatum in response to contextual cues. This is the first study to demonstrate an association between impaired striatal functioning and the rs2514218 polymorphism. We take our findings to indicate that striatal functioning is impaired in carriers of the DRD2 risk allele, likely due to dopamine dysregulation at the DRD2 location.

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Background:Schizophrenia is characterized by impairments in the fronto–striatal network. Underlying these impairments may be disruptions in anatomical pathways connecting frontal and striatal regions. However, the specifics of these disruptions remain unclear and whether these impairments are related to the genetic vulnerability of schizophrenia is not known.Methods:Here, we investigated fronto–striatal tract connections in 24 schizophrenia patients, 30 unaffected siblings, and 58 healthy controls using diffusion tensor imaging. Mean fractional anisotropy (FA) was calculated for tracts connecting the striatum with frontal cortex regions including the dorsolateral prefrontal cortex (DLPFC), medial orbital frontal cortex, and inferior frontal gyrus. Specifically, the striatum was divided into three subregions (caudate nucleus, putamen, and nucleus accumbens) and mean FA was computed for tracts originating from these striatal subregions.Results:We found no differences between patients, siblings, and controls in mean FA when taking the whole striatum as a seed region. However, subregion analyses showed reduced FA in the tract connecting the left nucleus accumbens and left DLPFC in both patients (P=0.0003) and siblings (P=0.0008) compared with controls.Conclusions:The result of reduced FA in the tract connecting the left nucleus accumbens and left DLPFC indicates a possible reduction of white matter integrity, commonly associated with schizophrenia. As both patients and unaffected siblings show reduced FA, this may represent a vulnerability factor for schizophrenia.

Child sexual abuse (CSA) is a worldwide problem with serious consequences. We hypothesized that worrisome sexual behavior and knowledge would frequently be reported in children assessed after CSA. We therefore investigated (A) what types of sexual behaviors and knowledge were reported by parents of young children assessed for CSA; (B) in what cases such behaviors and knowledge were worrisome; and (C) how such children responded verbally and non-verbally during child interviews. We conducted a mixed-methods study, including qualitative inductive content analysis and quantitative analysis. It included 125 children (76 boys, 60.8%; median age 3.3 years, age range 0–11), all involved in the Amsterdam sexual abuse case (ASAC) and examined for highly suspected (n = 71) or confirmed CSA (n = 54). We identified themes from (1) the parent reports: sexual behavior (e.g., self-stimulation, touching others, imitation of sexual acts), fears and anxiety with regard to sexuality, and sexual utterances (sexual slang, references to sexual acts); and (2) the child interviews: behavioral reactions (avoidance, distractive behaviors), emotional reactions (anger, aggression), and verbal reactions (conspicuous utterances, refusal to talk about specific subjects). In 37% of the children the sexual behavior was deemed worrisome or very worrisome. Clinicians who assess children for CSA are advised to focus in particular on sexual behavior problems and inappropriate sexual knowledge.

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