Glymphatic dysfunction and myelin disruption in subthreshold depression

Glymphatic dysfunction has been established in subthreshold depression (SD), but whether myelin content is altered and how it relates to glymphatic function remain unknown.

A total of 104 individuals with SD and 91 healthy controls (HCs) were recruited in the study. Depressive symptoms were assessed using Hamilton Depression Rating Scale (HAMD). Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was used to evaluate glymphatic function. Qseudo-quantitative inhomogeneous magnetization transfer (qihMT) and ihMT ratio (ihMTR) were obtained to evaluate myelin content. Finally, we observed the changes of the above indicators in individuals with SD after treatment.

Compared to HCs, individuals with SD showed reduced left DTI-ALPS, right DTI-ALPS, and mean DTI-ALPS. The qihMT values of the bilateral posterior thalamic radiation (PTR), right sagittal stratum (SS), and right uncinate fasciculus (UF), and the ihMTR values of the left PTR were both decreased in individuals with SD when compared to HCs. The left DTI-ALPS was positively correlated with qihMT values of the left PTR and right UF in individuals with SD. The hopelessness factor of HAMD was negatively correlated with qihMT values of the left PTR, right PTR, and right SS in individuals with SD. Preliminary within-group increases in DTI-ALPS and right PTR qihMT were observed after light therapy, with change in qihMT correlating with hopelessness improvement.

The impairments in myelin content in individuals at the early stages of depression were associated with glymphatic dysfunction.