The role of fronto-limbic network in suicide: a descriptive literature review of neuroimaging studies

Biol Psychiatry. 2025 Nov 8:S0006-3223(25)01604-X. doi: 10.1016/j.biopsych.2025.10.035. Online ahead of print.

ABSTRACT

Suicide is a complex public health issue characterized by impairments in emotion regulation and cognitive control. Identifying the brain substrates of suicide is critical for developing targeted and effective prevention strategies. Given the central role of the fronto-limbic network in affective processing and executive functioning, this review aimed to summarize neuroimaging findings on the fronto-limbic network associated with suicidal thoughts and behaviors (STBs). We first reviewed structural and functional neuroimaging studies published over the past decade reporting fronto-limbic network changes in individuals with a history of suicidal ideation or attempt. Next, we discussed the role of the fronto-limbic network in suicide, progressing from abnormalities in individual brain regions to structural and functional connectivity disruptions within this network. The reviewed literature suggests some convergent fronto-limbic network alterations related to STBs. First, structural atrophy of the fronto-limbic regions is generally observed, while heterogeneous functional changes exist. The prefrontal deficits in structure and function are right-lateralized, aligning with the right-hemisphere dominance in negative emotion processing. Second, the anterior cingulate cortex may serve as a hub of the fronto-limbic circuit, enabling the integration and coordination of neural processes between the prefrontal cortex and limbic regions. Finally, the fronto-limbic network exhibits a shift from early compensation to late decompensation in individuals with STBs, indicating exhaustion of compensatory mechanisms and loss of top-down control in suicide as the illness progresses. The comprehensive description of fronto-limbic network characteristics may advance the understanding of suicide from a network perspective and provide insights into therapeutic targets for suicide interventions.

PMID:41213392 | DOI:10.1016/j.biopsych.2025.10.035