White matter abnormalities in major depression: evidence from post-mortem, neuroimaging and genetic studies

Until more recently, most studies have examined the changes in brain gray matter in major depressive disorder (MDD) with less studies focusing on understanding white matter pathology in MDD. Studies of brain white matter volume changes, connectivity disruptions, as well as genetic factors affecting myelination can throw light on the nature of white matter abnormalities underpinning MDD.

We review the state of the art understanding of white matter changes in MDD from the extant neuropathology, neuroimaging and neurogenetic studies.

Overall, data are sparse and mostly conducted in older patients with MDD. Post-mortem studies have highlighted pathology of white matter in prefrontal brain region in terms of decreased oligodendrocyte density, reductions in the expression of genes related to oligodendrocyte function, molecular changes in intercellular cell adhesion molecule (ICAM) expression levels and suggestion of possible mechanism of ischemia. Structural magnetic resonance imaging studies have revealed deep white matter hyperintensities which are associated with clinical severity, and treatment responsiveness.

There is a particular dearth of genetic studies related to white matter pathology, studies of younger depressed subjects and specifically probing cortical and subcortical white matter pathology together in MDD.

Future investigations would want to study white matter changes in different cerebral regions and incorporate multimodal and longitudinal levels of examination in order to better grasp the neural basis of this condition.