Hippocampal activity may be biomarker for schizophrenia



Tracking activity in the hippocampus might provide a way to measure the effectiveness of therapeutic agents in patients with schizophrenia, a new study suggests.

"Intrinsic hyperactivity may contribute to the inability of the [hippocampal] region to be recruited during cognitive tasks in which it is thought to be required, such as image encoding and verbal encoding," wrote Jason R. Tregellas, Ph.D., and his associates. "The observed hyperactivity both supports models of hippocampal dysfunction and schizophrenia and increases the appeal of this measure as a potential biomarker," they reported (Am. J. Psychiatry 2014;171:549-56).

The researchers compared functional magnetic resonance imaging (fMRI) scans of the brains of 28 patients with schizophrenia, all taking antipsychotics, to the scans of 28 healthy controls, matched by age, while at rest. The schizophrenia patients also were assessed for negative symptoms, and all participants underwent cognitive function assessment with the MCCB (MATRICS Consensus Cognitive Battery), reported Dr. Tregellas of the psychiatry department at the University of Colorado at Denver, Aurora, and the Denver Veterans Affairs Medical Center Research Service, and his associates.

Although the schizophrenia patients scored within 1 standard deviation of the healthy controls’ scores in the verbal learning, working memory, visual learning, and reasoning/problem-solving domains on the MCCB, the schizophrenia patients’ scores were at least 1 standard deviation lower than the controls’ for processing speed, attention/vigilance, social cognition, and overall composite score.

The fMRI scans showed considerably greater intrinsic activity in the right hippocampus of the schizophrenia patients, compared with the controls’ hippocampal activity. The right hippocampal activity in the schizophrenia patients also was negatively correlated with their MCCB composite score (R = –0.53; P = .004), primarily because of the negative correlation with vigilance, working memory, and visual learning domains.

The right hippocampal activity in schizophrenia patients was positively correlated with their total SANS (Scale for the Assessment of Negative Symptoms) scores (R = 0.42; P = .028), but no correlation was seen with scores from the Brief Psychiatric Rating Scale. Total SANS scores were meanwhile negatively correlated with the MCCB working memory scores (R = –0.45; P = .016) and verbal learning scores (R = –0.45; P = .017).

Several limitations of the study were cited. For example, the investigators said it is unclear whether the association between hippocampal hyperactivity and cognitive function is specific to schizophrenia. "Studies examining MCCB performance and hippocampal activity in healthy subjects and other populations (e.g., patients with bipolar disorder) are needed to examine this possibility," the authors wrote.

The study was supported by the National Institute of Mental Health, the VA Biomedical Laboratory and Clinical Science Research and Development Service, the Brain and Behavior Research Foundation, and the Blowitz-Ridgeway Foundation. The authors reported that they had no financial relationships with commercial interests.

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