Striatal function in relation to negative symptoms in schizophrenia

Background. Previous studies have suggested that motivational aspects of executive functioning, which may be disrupted in schizophrenia patients with negative symptoms, are mediated in part by the striatum. Negative symptoms have been linked to impaired recruitment of both the striatum and the dorsolateral prefrontal cortex (DLPFC). Here we tested the hypothesis that negative symptoms are associated primarily with striatal dysfunction, using functional magnetic resonance imaging (fMRI). Method. Working-memory load-dependent activation and gray matter volumes of the striatum and DLPFC were measured using a region-of-interest (ROI) approach, in 147 schizophrenia patients and 160 healthy controls. In addition to testing for a linear relationships between striatal function and negative symptoms, we chose a second, categorical analytic strategy in which we compared three demographically and behaviorally matched subgroups: patients with a high burden of negative symptoms, patients with minimal negative symptoms, and healthy subjects. Results. There were no differences in striatal response magnitudes between schizophrenia patients and healthy controls, but right DLPFC activity was higher in patients than in controls. Negative symptoms were inversely associated with striatal, but not DLPFC, activity. In addition, patients with a high burden of negative symptoms exhibited significantly lower bilateral striatal, but not DLPFC, activation than schizophrenia patients with minimal negative symptoms. Working memory performance, antipsychotic exposure and changes in gray matter volumes did not account for these differences. Conclusions. These data provide further evidence for a robust association between negative symptoms and diminished striatal activity. Future work will determine whether low striatal activity in schizophrenia patients could serve as a reliable biomarker for negative symptoms. Received 6 January 2011; Revised 20 May 2011; Accepted 6 June 2011; First published online 7 July 2011