Depression as a Disease of White Matter Network Disruption: Learning From Multiple Sclerosis

Depression is a common and debilitating psychiatric disorder that is associated with substantial morbidity and mortality. For nearly 40 years, scientists have attempted to localize depression in the brain with neuroimaging. Despite concerted research, many meta-analyses of neuroimaging research in depression have not identified a single brain region that, when lesioned, causes depression. However, recent work using coordinate and lesion network mapping has identified a distributed network from functional magnetic resonance imaging that is relevant for depression. In this review, we propose that multiple sclerosis (MS) is a powerful model to study the relationship between perturbations to white matter brain networks and depression. We highlight recent successes in using lesion network mapping to find associations between depression and MS lesion location and burden in retrospective samples. Next, we describe why prospective, longitudinal studies that track the onset of white matter lesions in MS with the emergence and resolution of depression may provide a way to understand both the pathophysiology of depression in MS and network mechanisms of depression more broadly.