Adolescence is a period marked by high vulnerability to onset of depression. Neuroimaging studies have revealed considerableatrophy of brain structure in patients with major depressive disorder (MDD). However, the causal structural networks underpinning gray matter atrophies in depressed adolescents remain unclear. This study aimed to examine the initial gray matter alterations in MDD adolescents and investigate their causal relationships of abnormalities within brain structural networks.

First-episode adolescent patients with MDD (n = 80, age = 15.57 ± 1.78) and age- and sex-matched healthy controls (n = 82, age = 16.11 ± 2.76) were included. We analyzed T1-weighted structural images using voxel-based morphometry to identify gray matter alterations in patients and the disease stage-specific abnormalities. Granger causality analysis was then conducted to construct causal structural covariance networks. We also identified potential pathways between the causal source and target.

Compared to controls, MDD patients with shorter illness duration showed gray matter atrophy in localized brain regions such as ventral medial prefrontal cortex (vmPFC), anterior cingulate cortex, and insula. With a prolonged course of MDD, gray matter atrophy extended to widespread brain areas. Causal network results demonstrated that early abnormalities had positive effects on the default mode, frontoparietal networks, and reward circuits. Moreover, vmPFC demonstrated the highest out-degree value, possibly representing the initial source of brain abnormality in adolescent depression.

These findings revealed the progression of gray matter atrophy in adolescent depression and demonstrated the directional influences between initial localized alterations and subsequent deterioration in widespread brain networks.