Linked multimodal brain alterations in depression with suicidal risk

Suicidal ideation and behavior (SIB) represent a major clinical challenge in major depressive disorder (MDD), yet the multimodal brain structural signatures associated with SIB and their relationships with cognitive dysfunction remain poorly understood. We acquired multimodal neuroimaging measures, including gray matter volume, cortical thickness, pial area (PA), white matter fractional anisotropy, together with neurocognitive measures from 61 MDD patients with SIB (MDD-SIB), 38 without SIB (MDD-nSIB), and 142 healthy controls (HC). Linked independent component analysis (LICA) was used to identify covarying multimodal structural brain patterns, followed by group comparisons and exploratory association analyses. LICA identified distinct multimodal structural patterns related to SIB status, with IC1, IC9, and IC14 differing between MDD-SIB and HC, and IC12 between MDD-SIB and MDD-nSIB. Spatial working memory (SWM), visual memory, sustained attention, and cognitive flexibility also differed significantly across groups, with the MDD-SIB group showing poorer performance across these cognitive domains. Within the MDD-SIB group, IC1, a fronto-temporal-cingulate structural covariance pattern characterized predominantly by PA alterations, was associated with both SWM strategy performance and depressive symptom severity. These findings identify distributed multimodal structural signatures associated with SIB in MDD and highlight a fronto-temporal-cingulate neural correlate linking cognitive dysfunction with depressive symptom severity.