In Ch. 2, data were presented defining the phenomenology of depression associated with MS. This is an essential precursor to studies that have explored the etiology of mood change. Indeed, some of the difficulties in determining which symptoms most accurately reflect mood change in MS patients may account, in part, for the inconsistencies in the neuroimaging data. It is, therefore, no coincidence that as symptom clarification proceeds in tandem with advances in neuroimaging brain–behavior correlations have become more robust.

This chapter will explore, first, putative etiological factors in relation to depression, namely genetics, brain imaging changes, endocrine dysfunction, immune system abnormalities and diverse psychosocial theories. Thereafter, a review of treatment modalities for depressed MS patients will be presented.

Etiology of depression in multiple sclerosis

The pathogenesis of the major depressive-like disorders frequently experienced by MS patients is unclear. Research has been undertaken to examine mood and MS using genetics, structural and functional neuroimaging, endocrine and immune system markers and social variables, and a mixed picture has emerged. The reasons for these partial successes and failures are reviewed and future research options suggested.

Genetics and depression

Evidence suggesting a genetic link between MS and unipolar depression is mixed. Based on the family history method, Joffe et al. (1987) did not find an excess of affective illness in the first-degree relatives of patients with MS, a finding in agreement with others (Minden et al., 1987; Schiffer et al., 1988).