Alterations of brainstem volume in patients with first-episode and recurrent major depressive disorder

BACKGROUND: Major depressive disorder (MDD) is a prevalent mental health condition characterized by recurrent episodes in a substantial proportion of patients. The number of previous episodes is one of the most crucial predictors of depression recurrence. However, the underlying neural mechanisms remain unclear. To date, there have been limited neuroimaging studies investigating morphological changes of the brainstem in patients with first-episode MDD (FMDD) and recurrent MDD (RMDD). This study aimed to examine volumetric changes of individual brainstem regions in relation to the number of previous episodes and disease duration. METHOD: A total of 111 individuals including 36 FMDD, 25 RMDD, and 50 healthy controls (HCs) underwent T1-weighted structural magnetic resonance imaging scans. A Bayesian segmentation algorithm was used to analyze the volume of each brainstem region, including the medulla oblongata, pons, midbrain, and superior cerebellar peduncle (SCP), as well as the whole brainstem volume. Analyses of variance (ANOVA) were performed to obtain brain regions with significant differences among three groups and then post hoc tests were calculated for inter-group comparisons. Partial correlation analyses were further conducted to identify associations between regional volumes and clinical features. RESULTS: The ANOVA revealed significant brainstem volumetric differences among three groups in the pons, midbrain, SCP, and the whole brainstem (F = 3.996 ~ 5.886, adjusted p = 0.015 ~ 0.028). As compared with HCs, both groups of MDD patients showed decreased volumes in the pons as well as the entire brainstem (p = 0.002 ~ 0.034), however, only the FMDD group demonstrated a significantly reduced volume in the midbrain (p = 0.003). Specifically, the RMDD group exhibited significantly decreased SCP volume when comparing to both FMDD (p = 0.021) group and HCs (p = 0.008). Correlation analyses revealed that the SCP volumes were negatively associated with the number of depressive episodes (r=-0.36, p < 0.01) and illness duration (r=-0.28, p = 0.035) in patients with MDD. CONCLUSION: The present findings provided evidence of decreased brainstem volume involving in the pathophysiology of MDD, particularly, volumetric reduction in the SCP might represent a neurobiological marker for RMDD. Further research is needed to confirm our observations and deepen our understanding of the neural mechanisms underlying depression recurrence.