Psychological Medicine

Original Articles

Striatal function in relation to negative symptoms in schizophrenia

S. Ehrlicha1a2a3 c1, A. Yendikia1, D. N. Grevea1, D. S. Manoacha1a2, B.-C. Hoa4, T. Whitea5, S. C. Schulza5, D. C. Goffa2, R. L. Golluba1a2 and D. J. Holta1a2

a1 MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA

a2 Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA

a3 Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany

a4 Department of Psychiatry, University of Iowa, Iowa City, IA, USA

a5 Department of Psychiatry and the Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA


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 January 06 2011)

(Revised May 20 2011)

(Accepted June 06 2011)

(Online publication July 07 2011)


c1 Address for correspondence: S. Ehrlich, M.D., Massachusetts General Hospital/Harvard Medical School, Athinoula A. Martinos Center for Biomedical Imaging, Psychiatric Neuroimaging Research Program, CNY Building 120, Suite 100, Charlestown, MA 02129-2000, USA. (Email: