Suicide attempt history, childhood trauma, and functional brain network alterations in major depressive disorder: a resting-state functional connectivity-based multivariate pattern analysis

Abstract

A history of suicide attempts is one of the strongest predictors of future suicidal behavior in major depressive disorder (MDD). However, the resting-state functional connectivity (rs-FC) alterations that specifically differentiate MDD patients with a suicidal attempt history (SD) from those without (NSD) remain poorly understood. This study aimed to identify suicide attempt-specific rs-FC alterations using a two-stage multivariate pattern analysis (MVPA) framework-first contrasting the MDD group with the healthy control (HC) group, then directly comparing the SD group with the NSD group-and to examine whether the identified FC features were related to suicidal ideation or childhood trauma. Rs-FC data were collected from 204 adults (61 SD, 62 NSD, 81 HCs). Significant clusters from each MVPA were used as regions of interest (ROIs) for follow-up ROI-to-ROI and seed-to-voxel analyses, and associations with the Beck Scale for Suicide Ideation (SSI) and Childhood Trauma Questionnaire (CTQ) scores were examined. FC patterns that distinguished the SD group from the NSD group consistently involved visual network regions. The SD group showed lower FC between visual areas and prefrontal regions. Among ROI-level differences, the right intracalcarine cortex-right inferior temporal gyrus FC showed a negative correlation with CTQ-physical neglect subscale scores in the SD group (r = -0.427, pFDR = 0.017). Seed-to-voxel analyses revealed that lower visual-frontal FC was associated with greater suicidal ideation in the MDD group (e.g., left cuneus-left frontal pole, r = -0.341, pFDR = 0.023). These findings suggest a dysfunctional brain network linking childhood trauma, disrupted sensory-cognitive integration, and suicide attempt risk in MDD.