Gray matter abnormalities and associated familial risk endophenotype in individuals with first-episode bipolar disorder: Evidence from whole-brain voxel-wise meta-analysis.

Gray matter abnormalities have been widely reported in individuals with and at familial risk for bipolar disorder (BD). However, inconsistent findings were reported, and whether shared abnormalities exist between at-risk individuals and patients which can represent an endophenotype remained unclear. This meta-analysis aimed at identifying robust patterns of gray matter changes in patients with first-episode BD (FEBD) and associated risk endophenotype of BD. A systematic literature search was performed to identify eligible voxel-based morphometry studies comparing FEBD patients and healthy controls. Findings of included studies were integrated using the Seed-based d Mapping toolbox. Common and distinct patterns of gray matter abnormalities between FEBD patients and unaffected at-risk individuals were explored. A total of 16 VBM studies comparing 411 FEBD patients and 521 controls were included. FEBD patients showed increased gray matter volume in the cerebellum, posterior cingulate cortex and striatum, and decreased gray matter volume in the medial superior frontal gyrus and gyrus rectus. No common abnormalities were identified between FEBD patients and unaffected at-risk individuals. More gray matter loss in the medial superior frontal gyrus and insula were found in FEBD patients relative to unaffected at-risk individuals. These findings revealed robust gray matter abnormalities in the cortico-striato-cerebellar and default mode network regions in FEBD, and implicated that gray matter deficits may not represent a familial risk endophenotype of BD.