Distinct effects of first-episode and recurrent major depression disorder on brain changes related to suicidal ideation: Evidence from the REST-meta-MDD Project

Significant differences in clinical manifestations between first-episode and recurrent major depression disorder (FE-MDD/R-MDD) have been demonstrated in previous studies, including the degree of suicide attempt. However, the potential brain mechanism underlying the effect of depressive episode frequency on suicidal ideation (SI) remains unclear. In this study, 102 patients with FE-MDD (SI/non-SI: N = 70/32) and 71 matched normal controls (NCs), as well as 75 patients with R-MDD (SI/non-SI: N = 37/38) and 49 matched NCs were screened from the Chinese REST-meta-MDD consortium. T1-weighted and resting-state fMRI images were used to calculate gray matter volume (GMV) and fractional amplitude of low-frequency fluctuations (fALFF), respectively. Group comparisons revealed that FE-MDD showed changes only in GMV, while R-MDD showed changes in both GMV and fALFF compared to NCs. SI-specific GMV decreases were observed in the right cerebellum, superior marginal gyrus, and left middle temporal gyrus in FE-MDD patients, while SI-specific fALFF decreases were observed in bilateral superior frontal gyrus and increases in bilateral cerebellum and left parahippocampal gyrus in R-MDD patients. Moreover, a negative correlation was found between GMV value in right cerebellum and HAMD score. These findings suggest that first-episode and recurrent MDD show different effects on brain structure and function in patients with SI, providing a potential explanation for the distinct clinical manifestations of MDD patients from a brain mechanisms perspective.