Identifying both the commonalities and differences in brain structures among psychiatric disorders is important for understanding the pathophysiology. Recently, the ENIGMA-Schizophrenia DTI Working Group performed a large-scale meta-analysis and reported widespread white matter microstructural alterations in schizophrenia; however, no similar crossdisorder study has been carried out to date. Here, we conducted mega-analyses comparing white matter microstructural differences between healthy comparison subjects (HCS; N = 1506) and patients with schizophrenia (N = 696), bipolar disorder (N = 211), autism spectrum disorder (N = 126), or major depressive disorder (N = 398; total N = 2937 from 12 sites). In comparison with HCS, we found that schizophrenia, bipolar disorder, and autism spectrum disorder share similar white matter microstructural differences in the body of the corpus callosum; schizophrenia and bipolar disorder featured comparable changes in the limbic system, such as the fornix and cingulum. By comparison, alterations in tracts connecting neocortical areas, such as the uncinate fasciculus, were observed only in schizophrenia. No significant difference was found in major depressive disorder. In a direct comparison between schizophrenia and bipolar disorder, there were no significant differences. Significant differences between schizophrenia/bipolar disorder and major depressive disorder were found in the limbic system, which were similar to the differences in schizophrenia and bipolar disorder relative to HCS. While schizophrenia and bipolar disorder may have similar pathological characteristics, the biological characteristics of major depressive disorder may be close to those of HCS. Our findings provide insights into nosology and encourage further investigations of shared and unique pathophysiology of psychiatric disorders.

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Recent researches have suggested that brain-derived neurotrophic factor (BDNF) may be implicated in the pathophysiology of mood disorder. This study examined the association between the BDNF Val66Met polymorphism and major depressive disorder (MDD) in a Japanese population. We genotyped the BDNF Val66Met polymorphism in 154 major depressive patients and 154 age- and sex-matched control subjects. The genotypic distributions and allele frequencies were similar among the patients and control subjects. When the relationships of the polymorphism with several clinical variables (i.e., age, sex, age of onset, number of episode, presence of psychotic features, suicidal behavior, and family history) were examined, the dose of Met allele had significant effects on psychotic feature and suicidal behavior and family history. These results suggest that the BDNF Val66Met polymorphism is not related to the development of MDD but related to clinical features of MDD in a Japanese population.