Meta-analysis of brain and cranial size in schizophrenia.

Several meta-analyses are presented that address the issue of brain and/or cranial size reductions in schizophrenia. Separate meta-analyses were conducted for brain size (n = 27 studies), intracranial size (n = 18) or extracranial size (n = 8). For each meta-analysis, the weighted composite effect size (d) was tested for statistical significance (the direction of the effect size was negative if patients with schizophrenia had smaller structure size than controls). The influence of several potential modifiers of effect size (age, methods, region, gender) was individually evaluated. The composite effect sizes for studies of brain, intracranial and extracranial measures were d = -0.26, (p < 0.0001), d = -0.18, (p = 0.0012), and d = +0.14, (p = 0.16), respectively. Thus, the review found evidence for a small, but statistically significant reduction in brain and intracranial size in schizophrenia, but no evidence for a reduction in extracranial size. Studies based on axial image slices had significantly larger effects (d = -0.60) than the studies based on sagittal images (d = -0.09) (chi(2) = 14.0, p = 0.0002). In summary, the findings clearly support a small yet highly significant reduction of brain and intracranial size in schizophrenia.