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Articles   |    
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;171:549-556. doi:10.1176/appi.ajp.2013.13070981
View Author and Article Information

The authors report no financial relationships with commercial interests.

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.

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.

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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FIGURE 1. Hippocampal Activity in Patients With Schizophrenia and Healthy Comparison Subjectsa

a Intrinsic resting hippocampal activity is shown in healthy subjects (panel A) and in patients with schizophrenia (panel B), with the statistical parametric map thresholded at p<0.001. Panel C shows the hippocampal region of interest used. Activity and region of interest are overlaid on a group average anatomical scan for visualization.

FIGURE 2. Intrinsic Resting Hippocampal Activity in Patients With Schizophrenia (N=28) and Healthy Comparison Subjects (N=28)a

a Error bars indicate standard deviation.

FIGURE 3. Associations Between Cognition Measures and Intrinsic Hippocampal Activity in Schizophrenia Patients (N=28)a

a Panel A shows a significant association between cognition, as measured by the composite score on the MATRICS Consensus Cognitive Battery (MCCB) and intrinsic hippocampal activity in patients. Panel B shows results of an exploratory analysis of the relationships between MCCB domains and hippocampal activity.

FIGURE 4. Associations Between Negative Symptoms and Intrinsic Hippocampal Activity in Schizophrenia Patients (N=28)a

a Negative symptoms are assessed with the Scale for the Assessment of Negative Symptoms (SANS).

Anchor for Jump
TABLE 1.Relationships Between Right Hippocampal Activity and MCCB Composite Score, MCCB Domains, and Symptomsa
Table Footer Note

a BPRS=Brief Psychiatric Rating Scale; MCCB=MATRICS Consensus Cognitive Battery; SANS=Scale for the Assessment of Negative Symptoms.

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