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Hippocampal Resting Activity in Schizophrenia: A Biomarker of Cognitive Dysfunction?
Psych Progress
Hippocampal Resting Activity in Schizophrenia: A Biomarker of Cognitive Dysfunction?
Stephen I. Deutsch, MD, PhD
Ann Robinson Endowed Chair in Psychiatry, Professor and Chairman, Department of Psychiatry and Behavioral Sciences, Eastern Virginia Medical School; Attending Psychiatrist, Sentara Norfolk General Hospital, Norfolk, Va.
First published in Psychiatry Weekly, Volume 9, Issue 9, June 23, 2014
Schizophrenia patients are reported to have structural (ie, lower volume) and functional (eg, increased resting metabolism) abnormalities of the hippocampus. Increased hippocampal resting activity seems to be a consistently observed finding in fMRI and positron emission tomography (PET) studies when schizophrenia patients are challenged with minimal or no-load cognitive tasks (eg, listening passively to noise). The goal of a recent study was to determine whether increased hippocampal intrinsic “resting activity” could serve as a biomarker that could be targeted in pharmacotherapeutic trials designed to improve cognition in schizophrenia, which is a therapeutically neglected symptom domain most associated with failures to achieve competitive employment and independent living.
Subjects included 28 schizophrenia patients and 28 age- and gender-matched controls. Resting state activity was ascertained during a 10-minute fMRI scan with subjects “instructed to rest with their eyes open.” Participants also completed the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB), which assesses cognitive performance in seven domains in addition to providing a composite score. The researchers hypothesized that an inverse relation would be found between intrinsic hippocampal resting state activity and cognitive performance.
Intrinsic activity in the resting scans of the patients was significantly higher in the right hippocampus of the schizophrenia patients than the controls. Curiously, a significant difference between groups did not emerge for the left hippocampus. With respect to cognition, the patient group scored more than one standard deviation below the mean overall cognitive function scores of the controls, and particularly in the domains of processing speed, attention/vigilance, and social cognition. Moreover, significant inverse relations were found within the patient group between intrinsic resting activity in the right hippocampus and the MCCB composite score and the following discrete domain scores: attention/vigilance, working memory, and visual learning. There was a trend for significant inverse correlations between right-sided hippocampal intrinsic resting activity and verbal learning and social cognition, but there was a significant correlation between right-sided resting activity and an avolition subscore. Moreover, significant inverse relations were observed between total negative symptom scores and the scores for working memory and verbal learning from the MCCB.
These data support a role for hippocampal dysfunction in the cognitive disturbances and negative symptoms manifested by patients with schizophrenia. The data also suggest that this functional neuroimaging measure reflects core domains of psychopathology in schizophrenia (ie, cognitive dysfunction and negative symptoms) and could serve as a biomarker for target engagement. Theoretically, the existence of a validated biomarker would facilitate rapid screening of promising candidate medications for schizophrenia, shortening the amount of time it takes to bring a medicine from the bench to the bedside.
Disclosure: Dr. Deutsch has received grant support from the Commonwealth Health Research Board (State of Virginia).
Reference:
Tregellas JR, Smucny J, Harris JG, et al. Intrinsic hippocampal activity as a biomarker for cognition and symptoms in schizophrenia. Am J Psychiatry. 2014;171:549-556.