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Context: Smaller brain volumes have consistently been found in patients with schizophrenia, particularly in gray matter and medial temporal lobe structures. Although several studies have investigated brain volumes in nonpsychotic relatives of patients with schizophrenia, results have been inconsistent.Objective: To determine the magnitude and extent of brain volume differences in first-degree relatives of schizophrenic patients.Data Sources: A systematic search was conducted to identify relevant studies. Computer searches of the MEDLINE database were performed for English-language articles published before July 2005. Relevant abstracts published in 2005 were also selected.Study Selection: Magnetic resonance imaging studies that examined differences in brain volumes between first-degree relatives of patients with schizophrenia and healthy control subjects were obtained through computerized databases, including MEDLINE. Studies had to report sufficient data for computation of effect sizes.Data Extraction: For each study, the Cohen d was calculated. Data extraction and calculation of the effect size were performed by 2 authors ( H. B. M. B. and A. A.) who reached a consensus in cases of uncertainty and discrepancies. All analyses were performed using the random-effects model.Data Synthesis: Twenty-five studies were identified as suitable for analysis and included 1065 independent first-degree relatives of patients, 679 patients with schizophrenia, and 1100 healthy control subjects. The largest difference between relatives and healthy control subjects was found in hippocampal volume, with relatives having smaller volumes than controls (d=0.31; 95% confidence interval [CI], 0.13-0.49; 9 effect sizes). Gray matter was smaller (d=0.18; 95% CI, 0.02-0.33; 7 effect sizes) and third-ventricle volume was larger (d=0.21; 95% CI, 0.03-0.40; 7 effect sizes) in relatives compared with healthy control subjects.Conclusion: Brain abnormalities are present in nonpsychotic first-degree relatives of patients with schizophrenia and are most pronounced in the hippocampus.