Multilevel dynamic abnormalities of suicidal ideation in major depressive disorder from regional dynamics to network...

Suicidal ideation (SI) is a major clinical concern in major depressive disorder (MDD), yet its dynamic neural mechanisms remain poorly understood.

A total of 237 MDD patients (109 MDD-SI and 128 MDD-NSI) were included in the baseline analyses, and 89 patients with baseline SI were included in the longitudinal analyses following 8 weeks of selective serotonin reuptake inhibitor (SSRI) treatment. Dynamic amplitude of low-frequency fluctuations (dALFF), dynamic functional connectivity (dFC), dynamic brain network state analyses, and exploratory spatial neurotransmitter mapping were performed.

Compared with MDD-NSI, MDD-SI exhibited increased dALFF in the right precentral gyrus, left calcarine cortex, left supplementary motor area, left putamen, and left pregenual anterior cingulate cortex, positively associated with trait SI severity. In exploratory analyses, stronger left calcarine-precuneus dFC was associated with greater recent SI severity. Furthermore, dynamic network analyses identified two recurrent states. Greater recent SI severity showed a potential association with increased persistence in a hyperconnected state, characterized by enhanced intra-network connectivity within the somatomotor, visual, and ventral attention systems. Longitudinally, greater SI reduction among SSRI responders showed a potential association with reduced transition toward the hyperconnected brain state. Exploratory analyses showed spatial associations between SI-related dALFF abnormalities and multiple neurotransmitter systems.

The somatomotor and visual systems are consistently implicated in MDD-SI. Moreover, regional and network-level dynamic abnormalities may differentially contribute to trait SI, recent SI, and treatment-related improvements. Together with exploratory neurotransmitter associations, these findings provide a multi-level perspective on the dynamic neural mechanisms of suicidality, which warrants further validation.