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Intrinsic Hippocampal Activity as a Biomarker for Cognition and Symptoms in Schizophrenia
Jason R. Tregellas, Ph.D.; Jason Smucny, M.S.; Josette G. Harris, Ph.D.; Ann Olincy, M.D.; Keeran Maharajh, Ph.D.; Eugene Kronberg, Ph.D.; Lindsay C. Eichman, B.S.; Emma Lyons, B.S.; Robert Freedman, M.D.
Am J Psychiatry 2014;:. doi:10.1176/appi.ajp.2013.13070981
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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.

Address correspondence to Dr. Tregellas (jason.tregellas@ucdenver.edu).

Copyright © 2014 by the American Psychiatric Association

Received July 26, 2013; Revised October 18, 2013; Accepted November 12, 2013.

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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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