Multimodal Neural Evidence on the Corticostriatal Underpinning of Suicidality in Late-Life Depression

Abstract

Background: Suicidality involves thoughts (ideations and plans) and actions related to self-inflicted death. To improve management and prevention of suicidality, it is essential to understand the key neural mechanisms underlying suicidal thoughts and actions. Following empirically informed neural framework, we hypothesized that suicidal thoughts would be primarily characterized by alterations in the default mode network indicating disrupted self-related processing, whereas suicidal actions would be characterized by changes in the lateral prefrontal corticostriatal circuitries implicating compromised action control. Methods: We analyzed the gray matter volume and resting-state functional connectivity of 113 individuals with late-life depression, including 45 nonsuicidal patients, 33 with suicidal thoughts but no action, and 35 with past suicidal action. Between-group analyses revealed key neural features associated with suicidality. The functional directionality of the identified resting-state functional connectivity was examined using dynamic causal modeling to further elucidate its mechanistic nature. Post hoc classification analysis examined the contribution of the neural measures to suicide classification. Results: As expected, reduced gray matter volumes in the default mode network and lateral prefrontal regions characterized patients with suicidal thoughts and those with past suicidal actions compared with nonsuicidal patients. Furthermore, region-of-interest analyses revealed that the directionality and strength of the ventrolateral prefrontal cortex–caudate resting-state functional connectivity were related to suicidal thoughts and actions. The neural features significantly improved classification of suicidal thoughts and actions over that based on clinical and suicide questionnaire variables. Conclusions: Gray matter reductions in the default mode network and lateral prefrontal regions and the ventrolateral prefrontal cortex–caudate connectivity alterations characterized suicidal thoughts and actions in patients with late-life depression.