Depression Associated with Multiple Sclerosis: An Etiological Conundrum

OBJECTIVE: Although depression frequently occurs in multiple sclerosis (MS), an association with cerebral pathology is unclear. This sets MS apart from other common neurological disorders. The reasons for this are explored. METHOD: The literature on depression and magnetic resonance imaging (MRI) is reviewed and methodological issues are critically evaluated. RESULTS: Failure to demonstrate cerebral correlates of depression is in part a function of poor study design. However, the diffuse nature of cerebral demyelination creates difficulties in image analysis peculiar to MS. CONCLUSIONS: More research using valid psychiatric assessment procedures, high field strength MRI and automated lesion detection is needed to resolve the issue. It is premature to reject psychosocial causes at this stage.