Neuroimage Clin. 2025 Oct 22;48:103890. doi: 10.1016/j.nicl.2025.103890. Online ahead of print.
ABSTRACT
OBJECTIVES: Major depressive disorder (MDD) is a prevalent mental illness with unclear underlying pathophysiology that is often linked to childhood trauma. Emerging evidence suggests a potential association between myelin abnormalities and depression, highlighting the need for further understanding of these neurobiological connections in MDD patients. This study investigated the mediating role of abnormal myelin in the pathophysiology of MDD induced by childhood trauma via quantitative Synthetic Magnetic Resonance Imaging (SyMRI) technique.
METHODS: MDD patients and healthy controls underwent SyMRI scanning to assess myelin content, T1, T2 and proton density (PD) values in the brain. Statistical analyses compared these values between groups and correlated them with clinical symptom scores. Mediation analysis was used to determine the role of myelin content in the relationship between childhood trauma and clinical symptoms.
RESULTS: Thirty-five MDD patients (median age, 23[18-34] years, 7 men) and forty-nine healthy controls (median age, 24[21-35] years, 18 men) were included. Compared with healthy controls, MDD patients presented significantly lower myelin content (FDR-corrected p < 0.05; Cohen’s d = -0.85 – -0.75) and higher PD values (FDR-corrected p < 0.05; Cohen’s d = 0.71-0.94) in the left inferior frontal sulcus, left caudal area 45, left medial area 14, left rostral area 7, left lateral area 5, left ventral dysgranular and granular insula, and left nucleus accumbens. The T1 and T2 values were not significantly different (FDR-corrected p > 0.05). A lower myelin content was significantly correlated with higher depression and anxiety scores (p < 0.05; R = 0.1309-0.2550). A myelin reduction in the left lateral area 5 and left ventral dysgranular and granular insula mediated the association between childhood trauma and MDD symptoms (p < 0.05; β = 0.0643-0.0807).
CONCLUSION: Our findings suggest that reduced myelin content in the left lateral area 5 and left ventral dysgranular and granular insula, due to childhood trauma, mediated 6.4% to 8.1% of the variance of MDD. However, the cross-sectional design limits causal inference, and the influence of comorbid anxiety was not controlled.
PMID:41138696 | DOI:10.1016/j.nicl.2025.103890
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