Gray Matter Volume Alterations in Early-Adulthood Major Depressive Disorder Patients With Non-Suicidal Self-Injury and Suicide Attempts

BACKGROUND Major depressive disorder (MDD) is frequently accompanied by self-harm behaviors, including non-suicidal self-injury (NSSI) and suicide attempts (SA), which are important risk factors for suicide and poor clinical outcomes. Although neuroimaging studies have identified structural brain abnormalities related to suicidal behaviors in MDD, the neurobiological distinctions between NSSI and SA remain poorly understood. In particular, few studies have simultaneously compared MDD patients with NSSI, MDD patients with SA, and MDD patients without self-harm behaviors. Therefore, this study aimed to investigate gray matter volume (GMV) alterations and their associations with clinical symptoms in early-adulthood MDD patients using voxel-based morphometry (VBM). METHODS A total of 54 MDD patients with NSSI (MDD/NSSI), 68 MDD patients without NSSI (sMDD), 50 MDD patients with SA (MDD/SA), and 66 healthy controls (HC) were included. Voxel-based morphometry (VBM) was used to examine GMV differences using high-resolution T1-weighted MRI scans. Age, sex, education, and intracranial volume were included as covariates. One-way ANOVA with Gaussian random field (GRF) correction was performed, followed by post-hoc t-tests. Correlations between GMV and clinical measures of depression (HAMD), anxiety (HAMA), and suicide risk (NGASR) were assessed. RESULTS Significant GMV differences were found in the right superior/middle frontal gyrus, left superior frontal gyrus, bilateral caudate nuclei, right superior/middle temporal gyrus, and bilateral middle cingulate gyrus (voxel-level p < 0.001, GRF corrected p < 0.05). Compared to MDD/NSSI, the MDD/SA group showed reduced GMV in several regions. Correlations between GMV in the caudate nucleus and cingulate cortex with depression severity, anxiety, and suicide risk were observed, but did not survive FDR correction. CONCLUSIONS MDD patients with NSSI and SA show distinct GMV alterations. Findings suggest that MDD with SA involves unique neural impairments, contributing to emotional dysregulation and suicide risk.