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Abstract

Compared with healthy individuals, patients with schizophrenia had greater resting state hippocampal activity that was inversely related to schizophrenia symptoms and cognitive deficits, indicating a possible brain biomarker for developing cognitive therapies in schizophrenia.

Abstract

Objective

Identification of biomarkers for cognitive dysfunction in schizophrenia is a priority for psychiatry research. Functional imaging studies suggest that intrinsic “resting state” hippocampal hyperactivity is a characteristic feature of schizophrenia. The relationships between this phenotype and symptoms of the illness, however, are largely unexplored. The authors examined resting hippocampal activity in schizophrenia patients and healthy comparison subjects and analyzed the relationship between intrinsic hippocampal activity and cognitive function in patients as measured by the MATRICS Consensus Cognitive Battery (MCCB).

Method

Twenty-eight schizophrenia patients and 28 age-matched healthy comparison subjects underwent functional “resting state” 3-T MR scanning. Hippocampal activity was extracted by group independent component analysis. Correlation analyses were used to examine the relationship between hippocampal activity and MCCB composite and domain scores in patients, as well as between hippocampal activity and positive and negative symptoms.

Results

Greater activity of the right hippocampus at rest was observed in patients relative to comparison subjects. In patients, a significant negative correlation was observed between right hippocampal activity and composite MCCB T-score. The correlation was driven by the MCCB domains of attention/vigilance, working memory, and visual learning. Hippocampal activity was positively correlated with negative symptoms. MCCB scores were inversely correlated with negative symptoms.

Conclusions

These findings suggest that greater intrinsic hippocampal activity is a characteristic feature of schizophrenia that is broadly associated with cognitive dysfunction, and they support hippocampal activity as a candidate biomarker for therapeutic development.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 549 - 556
PubMed: 24435071

History

Received: 26 July 2013
Revision received: 18 October 2013
Accepted: 12 November 2013
Published online: 1 May 2014
Published in print: May 2014

Authors

Details

Jason R. Tregellas, Ph.D.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Jason Smucny, M.S.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Josette G. Harris, Ph.D.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Ann Olincy, M.D.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Keeran Maharajh, Ph.D.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Eugene Kronberg, Ph.D.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Lindsay C. Eichman, B.S.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Emma Lyons, B.S.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.
Robert Freedman, M.D.
From the Department of Psychiatry and the Neuroscience Program, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora; and the Research Service, Denver VA Medical Center, Denver.

Notes

Address correspondence to Dr. Tregellas ([email protected]).

Funding Information

The authors report no financial relationships with commercial interests.
Supplementary Material
Supported by NIMH Conte Center Grant MH-086383; the VA Biomedical Laboratory and Clinical Science Research and Development Service; the Brain and Behavior Research Foundation; and the Blowitz-Ridgeway Foundation.

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