Sex Differences in Cortical Structural Alterations in Major Depressive Disorder With Suicidal Ideation

Background: Previous studies have documented brain structural changes in major depressive disorder with suicidal ideation (MDDSI). While sex differences in brain structure have been observed in MDD, the specific differences in MDDSI remain underexplored. This study aims to examine sex-specific cortical structural changes in MDDSI patients, with the goal of improving suicide risk assessment and supporting the development of sex-specific interventions. Methods: High-resolution T1-weighted magnetic resonance imaging (MRI) data were acquired from 177 participants, including 117 patients with MDD (44 males and 73 females) and 60 healthy controls (HC; 23 males and 37 females). Using FreeSurfer, we assessed the main effects of both group and sex, as well as sex-by-group interactions, on cortical thickness (CT), surface area (SA), cortical volume (CV), and local gyrification index (LGI). Pearson partial correlation analysis was performed to examine the associations between sex-specific regions and SI scores. Results: Patients with MDDSI exhibited significantly reduced LGI in the right inferior and superior parietal cortices, irrespective of sex. Significant sex-by-group interactions were identified and post hoc analyses revealed that male MDDSI patients showed significantly greater CT in the right lingual gyrus (LG) compared to their female counterparts, along with smaller SA in the right lateral occipital cortex (LOC) and reduced CV in the right pericalcarine cortex (PCAL) compared to their sex-matched MDD patients without SI (MDDNonSI). No significant associations were found between these structural changes and SI scores. Conclusion: This study highlights sex-specific differences in cortical structures in MDDSI patients. These findings contribute to understanding the neurobiological mechanisms underlying MDD with SI. Trial Registration: Chinese Clinical Trial Registry (ChiCTR): ChiCTR2100049646.