Abstract Background Major depressive disorder (MDD) is closely associated with suicide, which often begins with suicidal ideation (SI). However, the underlying neural mechanisms remain unclear. Methods We included 73 MDD patients with SI (MDD-SI), 44 MDD patients without SI (MDD-NSI) and 78 healthy controls (HCs), then compared the amplitude of low-frequency fluctuations (ALFF), functional connectivity (FC), and effective connectivity (EC) differences across groups and analyzed their relationship with SI severity. FC and EC analyses used brain regions with ALFF differences between MDD-SI and MDD-NSI as seed points. ALFF findings were validated using the REST-meta-MDD consortium dataset (N = 1 596, 24 sites). Additionally, we explored the trend of changes in abnormal activity and connectivity of SI and suicidal behavior (SB) in MDD-SI. Results Compared to MDD-NSI, MDD-SI showed increased ALFF in the right anterior cingulate cortex (ACC), validated by the REST-meta-MDD consortium dataset. MDD-SI also exhibited reduced FC between the right ACC and the left inferior frontal gyrus and decreased EC from the right ACC to the right fusiform gyrus, which were negatively correlated with the Hamilton Depression Rating Scale (HAMD)-suicidality item scores. Increased EC was observed in MDD-SI from the right ACC to the right cerebellar tonsil and from the left inferior parietal lobule (IPL) to the right ACC, following a progressive increase pattern (HC < MDD-NSI < MDD-SI without SB < MDD-SI with SB). Conclusions Increased activity and aberrant connectivity of the ACC may be associated with SI in MDD patients and potentially serve as biomarkers for suicide risk.
Zhang et al. (Wed,) studied this question.