Research Review: Shared and distinct structural and functional brain alterations in adolescents with major depressive disorder' - a multimodal meta-analysis

Background: Neuroimaging studies have identified brain structural and functional alterations in adolescents with major depressive disorder (MDD); however, the results are inconsistent, and whether patients exhibit spatially convergent structural and functional brain abnormalities remains unclear.

Methods: We conducted voxel-wise meta-analysis of voxel-based morphometry (VBM) and resting-state functional studies, respectively, to identify regional gray matter volume (GMV) and brain activity alterations in adolescent MDD patients. Multimodal analysis was performed to examine the overlap of regional GMV and brain activity alterations. Meta-regression analysis was conducted to evaluate the potential effects of clinical variables.

Results: Ten whole-brain VBM studies (403 patients and 319 controls) and 14 resting-state functional studies (510 patients and 474 controls) were included. Adolescent MDD patients showed conjoint structural and functional alterations in the left medial/dorsolateral prefrontal cortex, lateral temporal cortex and sensorimotor regions, and left insula. Adolescent MDD patients showed structural-specific abnormalities in the subcortical and prefrontal-limbic regions and functional-specific abnormalities in the right insula, right superior occipital gyrus, left inferior frontal gyrus and left precuneus. Meta-regression analyses revealed that the mean age of adolescents with MDD was positively associated with GMV in the right superior temporal gyrus and negatively associated with brain activity in the right insula, and the symptom severity of adolescents with MDD was positively associated with brain activity in the right superior occipital gyrus.

Conclusions: This meta-analysis identified complicated patterns of conjoint and dissociated brain alterations in adolescent MDD patients, which may advance our understanding of the neurobiology of adolescent MDD.