Neural mechanisms of suicide thoughts and behaviors in major depressive disorder: abnormal regional brain activity and its functional connectivity.

BACKGROUND: Suicide thoughts and behaviors (STB), including suicidal ideation (SI) and suicide attempts (SA), are significant concerns in major depressive disorder (MDD), yet their neurobiological mechanisms remain poorly understood. This study aims to identify key regional brain activity and connectivity abnormalities associated with STB in MDD by combining a meta-analysis of regional brain activity comparing MDD patients with STB to non-STB controls (both MDD without STB and healthy controls) and an exploratory functional connectivity (FC) analysis in an independent sample of MDD patients. METHODS: A meta-analysis employing Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) software identified regional brain abnormalities. Studies included were those comparing MDD patients with STB to non-STB controls, employing resting-state fMRI with whole-brain analyses, using ALFF, fALFF, and ReHo metrics. The identified abnormal brain regions were used as regions of interest (ROIs) for FC analyses in 57 first-episode, drug-naive MDD patients. RESULTS: The meta-analysis included 12 studies (13 datasets) comprising 555 MDD patients with STB and 430 non-STB controls. Compared to non-STB controls, MDD-STB patients showed increased activity in the right middle occipital gyrus (MOG) and right inferior frontal gyrus, triangular part (IFGtriang), while decreased activity in right precuneus. Subgroup analysis of SA revealed increased activity in the left angular gyrus in MDD patients with SA, compared to non-SA controls. SI subgroup analysis and two medication status subgroup analyses showed no significant results. In independent sample, FC analysis yielded two significant FCs after Bonferroni correction. Correlation analysis showed a negative association between right MOG-IFGtriang FC and most severe SI scores measured by the Beck Scale for Suicidal Ideation (P = 0.04), though it was non-significant after correction. CONCLUSIONS: These findings provide novel insights into the neural mechanisms of STB in MDD, identifying specific brain regions and FC patterns associated with STB. These results align with prior studies, highlighting the role of visual processing and cognitive control regions in STB. By combining a meta-analysis of regional abnormalities with an exploratory FC analysis, this study offers a comprehensive understanding of the brain networks implicated in STB and suggests potential targets for future interventions.