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 (DMN) indicating disrupted self-related processing, whereas suicidal actions would be characterized by changes in the lateral prefrontal cortico-striatal circuitries implicating compromised action control. Methods We analysed the grey matter volume and resting-state functional connectivity (RSFC) of 113 individuals with late-life depression (LLD), including 45 non-suicidal 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 RSFC was examined using dynamic causal modelling to further elucidate its mechanistic nature. Post-hoc classification analysis examined the contribution of the neural measures to suicide classification. Results As expected, reduced grey matter volumes in DMN and lateral prefrontal regions characterized patients with suicidal thought and those with past suicidal actions compared to non-suicidal patients. Furthermore, region-of-interest analyses revealed the directionality and strength of the ventrolateral prefrontal cortex-caudate RSFC 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 Grey matter reductions in the DMN and lateral prefrontal regions, and the ventrolateral prefrontal cortex-caudate connectivity alterations, characterised suicidal thoughts and actions in LLD patients.