Hot suicidal ideation is associated with reduced ENIGMA-defined subcortical volumes in major depressive disorder

Large-scale neuroimaging research from the ENIGMA consortium has identified a significant subcortical signature of suicide attempt characterized by reduced thalamic and pallidal volumes. However, no comparable associations have been observed for suicidal ideation, despite being a precursor of suicidal behavior. This dissociation may reflect heterogeneity in how suicidal ideation is conceptualized. The thalamus and pallidum are subcortical hubs involved in emotional reactivity and action readiness, suggesting that alterations in these regions may relate more strongly to hot (affectively driven, unplanned) than to cold (deliberate, planned) suicidal ideation.

We analyzed structural MRI data from 263 individuals with major depressive disorder. Suicidal ideation subtype was derived from the MADRS suicide item. A thalamo-pallidal composite score was computed from ENIGMA-defined regions (bilateral thalamus and right pallidum) using z-scores. General linear models tested associations between ideation subtype and brain volumes, adjusting for age, sex, intracranial volume, depression severity, and history of suicide attempt.

Hot suicidal ideation was associated with reduced thalamo-pallidal volume compared with no suicidal ideation, whereas no significant association was observed for cold suicidal ideation. No significant associations were observed for DLPFC volume, and the association with hot suicidal ideation remained significant after controlling for DLPFC volume.

Findings suggest that ENIGMA's suicide-attempt signature may extend to a specific subtype of suicidal ideation and provide initial support for the distinction between hot and cold suicidal ideation. More broadly, differentiating ideation subtypes may reveal neurobiological associations that remain undetected when suicidal ideation is treated as a unitary construct.