Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies

Abstract Despite hundreds of structural MRI studies documenting smaller brain volumes on average in schizophrenia compared to controls, little attention has been paid to group differences in the variability of brain volumes. Examination of variability may help interpret mean group differences in brain volumes and aid in better understanding the heterogeneity of schizophrenia. Variability in 246 MRI studies was meta-analyzed for 13 structures that have shown medium to large mean effect sizes (Cohen’s d≥0.4): intracranial volume, total brain volume, lateral ventricles, third ventricle, total gray matter, frontal gray matter, prefrontal gray matter, temporal gray matter, superior temporal gyrus gray matter, planum temporale, hippocampus, fusiform gyrus, insula; and a control structure, caudate nucleus. No significant differences in variability in cortical/subcortical volumes were detected in schizophrenia relative to controls. In contrast, increased variability was found in schizophrenia compared to controls for intracranial and especially lateral and third ventricle volumes. These findings highlight the need for more attention to ventricles and detailed analyses of brain volume distributions to better elucidate the pathophysiology of schizophrenia.