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Striatal function in relation to negative symptoms in schizophrenia

Published online by Cambridge University Press:  07 July 2011

S. Ehrlich ,
A. Yendiki ,
D. N. Greve ,
D. S. Manoach ,
B.-C. Ho ,
T. White ,
S. C. Schulz ,
D. C. Goff ,
R. L. Gollub  and
D. J. Holt
S. Ehrlich*
Affiliation:
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA Department of Child and Adolescent Psychiatry, University Hospital Carl Gustav Carus, Dresden University of Technology, Germany
A. Yendiki
Affiliation:
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
D. N. Greve
Affiliation:
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA
D. S. Manoach
Affiliation:
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
B.-C. Ho
Affiliation:
Department of Psychiatry, University of Iowa, Iowa City, IA, USA
T. White
Affiliation:
Department of Psychiatry and the Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
S. C. Schulz
Affiliation:
Department of Psychiatry and the Center for Magnetic Resonance Research, University of Minnesota, Minneapolis, MN, USA
D. C. Goff
Affiliation:
Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
R. L. Gollub
Affiliation:
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
D. J. Holt
Affiliation:
MGH/MIT/HMS Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA
*
*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: [email protected])
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Abstract

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.

Keywords

Dorsolateral prefrontal cortexfunctional MRInegative symptomsschizophreniastriatum
Type
Original Articles
Information
Psychological Medicine , Volume 42 , Issue 2 , February 2012 , pp. 267 - 282
Copyright
Copyright © Cambridge University Press 2011

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