White matter hyperintensities and their role in major depressive episodes: a cross-sectional study in adults under 65

White matter hyperintensities (WMH) are associated with Major Depressive Episodes (MDE) in individuals aged 65 and over. WMH are prevalent in adults under 65, yet the association between their volume and MDE in this population remains uncertain. This study aimed to assess the association between WMH volume and MDE and its severity in patients < 65. This cross-sectional study included subjects under the age of 65, 69 patients with MDE and 32 healthy controls (HCs). Severity was assessed with the Hamilton Rating Scale and WMH were quantified by 2 experts. Post-hoc mediation analyses were conducted if associations were found between independent variables and WMH. Mean was 34.5 (12.4) years old. There was no difference in WMH between patients and HCs. Higher WMH volume were observed in extremely severe MDE (2170.2 (3767.9) mm3 vs 416.6 (594.9) mm3 (r = 0.21; p < 0.05)), which completely mediated the effect of age on severity. In adults under 65, this study failed to identify higher WMH volume in MDE compared to HCs. However, WMH may act as a mediator of the association between age and MDE severity. This finding suggests that WMH could contribute to more severe depression in late-life.