Resting-state mapping of neural signatures of vulnerability to depression relapse

Patients with major depressive disorder (MDD) can frequently develop new depressive episodes after remission. However, the neural mechanisms underlying the increased risk for depressive relapse remain unclear. Herein, we aimed to explore whether the specific changes to regional and inter-regional spontaneous brain activities within DMN are associated with the course of episodes in pooled MDD patients. Resting-state functional magnetic resonance imaging was performed on patients with single-episode MDD (SEMDD, n = 30) and multiple-episode MDD (MEMDD, n = 54), and 71 age-, gender-, and educational level-matched healthy controls (HCs). We then accessed the differences in both the fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity by using the right precuneus as the seed among different groups. Compared to the MEMDD and HC groups, the SEMDD group exhibited increased fALFF values in the right subgenual anterior cingulate cortex and right middle temporal gyrus. Decreased fALFF values in the right thalamus in the MEMDD group were also identified relative to the SEMDD and HC group. The peak values of fALFF in the right precuneus showed a negative correlation with the number of depressive episodes across the entire pool of MDD patients. No correlation was identified between functional connectivity using the right precuneus as the seed and the number of depressive episodes for the pooled MDD patients. Medication, a relatively small sample size, and hypothesis driven study. Our neuroimaging results identified depression relapse-associated neural signatures and also indicated the role of reduced emotional appraisals in the thalamus. It is now possible to believe that the regional activity not inter-regional connectivity within the DMN may be involved in the pathology of depression relapse.