Divergent Suicidal Symptomatic Activations Converge on Somato-cognitive Action Network in Depression

Abstract

Abstract Individuals with depression have the highest lifetime prevalence of suicide attempt (SA) among mental illnesses. Numerous neuroimaging studies have developed biomarkers from task-related neural activation in depressive patients with SA, but the findings are inconsistent. Empowered by the contemporary interconnected view of depression as a neural system disorder, we sought to identify a specific brain circuit utilizing published heterogeneous neural activations. We systematically reviewed all published cognitive and emotional task-related functional MRI studies that investigated differences in the location of neural activations between depressive patients with and without SA. We subsequently mapped underlying brain circuits functionally connected to each experimental activation using a large normative connectome database (n = 1 000). The identified SA-related functional network was compared with the network derived from the disease control group. Finally, we decoded this convergent functional network using microscale transcriptomic and chemo-architectures and macroscale psychological processes. We selected 11 experimental tasks from eight studies including depressive patients with SA (n = 147) and without SA (n = 196). The heterogeneous SA-related neural activations localized to the somato-cognitive action network (SCAN), exhibiting robustness to little perturbations and specificity to depression. Furthermore, the SA-related functional network colocalized with spatial expression of genes that are involved in inflammatory and immunity-related biological processes and aligned with the distribution of the GABA and noradrenaline neurotransmitter systems. The findings demonstrate that the SA-related functional network in depression predominantly involves the SCAN, which is robust and disease-specific, and have important implications for understanding depressive patients with SA.