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A Meta-analytic Study

Michael D. Nelson, MA; Andrew J. Saykin, PsyD; Laura A. Flashman, PhD; Henry J. Riordan, PhD

Arch Gen Psychiatry. 1998;55:433-440.

Background  Although many quantitative magnetic resonance imaging studies have found significant volume reductions in the hippocampi of patients with schizophrenia compared with those of normal control subjects, others have not. Therefore, the issue of hippocampal volume differences associated with schizophrenia remains in question.

Methods  Two meta-analyses were conducted to reduce the potential effects of sampling error and methodological differences in data acquisition and analysis. Eighteen studies with a total patient number of 522 and a total control number of 426 met the initial selection criteria.

Results  Meta-analysis 1 yielded mean effect sizes of 0.37 (P<.001) for the left hippocampus and 0.39 (P<.001) for the right, corresponding to a bilateral reduction of 4%. Meta-analysis 2 indicated that the inclusion of the amygdala in the region of interest significantly increased effect sizes across studies (effect size for the left hippocampus and amygdala, 0.67; for the right, 0.72), whereas variables such as illness duration, total slice width, magnet strength, the use of the intracranial volume as a covariate, measurement reliability, and study quality did not. No laterality differences were observed in these data.

Conclusions  Schizophrenia is associated with a bilateral volumetric reduction of the hippocampus and probably of the amygdala as well. These findings reinforce the importance of the medial temporal region in schizophrenia and are consistent with frequently reported memory deficits in these patients. Future quantitative magnetic resonance imaging studies evaluating the hippocampal volume should measure the hippocampus and amygdala separately and compare the volumetric reduction in these structures to that observed in other gray matter areas.

From the Department of Psychology, Dartmouth College, Hanover (Mr Nelson and Dr Saykin); the Brain Imaging Laboratory, Department of Psychiatry (Mr Nelson and Drs Saykin, Flashman, and Riordan), and the Department of Radiology (Dr Saykin), Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon; and the New Hampshire Hospital, Concord (Drs Saykin and Flashman), NH.

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