Major depressive disorder (MDD) tends to emerge during adolescence; however, neurobiological research in adolescents has lagged behind that in adults. This study aimed to characterize gray matter (GM) structural alterations in adolescents with MDD using comprehensive morphological analyses.

This study included 93 adolescent MDD patients and 77 healthy controls. Voxel-based morphometry (VBM), deformation-based morphometry (DBM), and surface-based morphometry (SBM) methods were used to analyze GM morphological alterations in adolescent MDD patients. Sex-by-group and age-by-group interactions, as well as the relationships between altered GM structure and clinical characteristics were also analyzed.

Whole-brain VBM and DBM analyses revealed GM atrophy in the left thalamus and bilateral midbrain in adolescent MDD patients. Whole-brain SBM analysis revealed that adolescent MDD patients, relative to controls, showed decreased thickness in the left postcentral gyrus and left precentral gyrus; increased thickness in the bilateral superior temporal gyrus, left parahippocampal gyrus and right lateral orbitofrontal gyrus; and decreased fractal dimension in the right lateral occipital gyrus. A significant sex-by-group interaction effect was found in the fractal dimension of the left lateral occipital gyrus. The volume of the left thalamus and the thickness of the left superior temporal gyrus were correlated with the duration of disease in adolescent MDD patients.

This study suggested that adolescent MDD had GM morphological abnormalities in the frontal-limbic, subcortical, perceptual network and midbrain regions, with some morphological abnormalities associated with disease duration and sex differences. These findings provide new insight into the neuroanatomical substrates underlying adolescent MDD.