Depression is one of the most common symptoms in patients with multiple sclerosis (MS) with a prevalence of up to 50%. Depression is linked to decreased cognitive function, lower quality of life, increases psychosocial and economic burden and is the strongest predictor of suicide.Despite the high clinical relevance, the pathogenetic substrates for depression in MS are poorly understood. Growing evidence suggests that it may be largely biologically mediated by some of the same processes involved in the immunopathogenesis of this neurologic disease. In particular, increases in proinflammatory cytokines, and activation of the hypothalamic-pituitary-adrenal (HPA) axis have independently been shown to be involved in major depressive disorder (MDD) as well as MS.Pregnancy is associated with profound changes in the endocrine and immune system and interestingly, the post partum period is characterized by a higher risk for relapses both in depression and MS. During pregnancy, in contrast, there is an approximately 80% reduction in MS relapse rate, an effect that is stronger than that achieved by any of the currently approved disease-modifying therapies. Thus, pregnancy is a powerful paradigm to study shared mechanisms of disease activity in MS and depression.In the proposed study, we will determine immunological and endocrine correlates of mood changes longitudinally in female relapsing-remitting MS patients during pregnancy and post partum. Clinical interviews and validated questionnaires will be used to examine depression incidence and severity. Blood samples for immune studies, salivary cortisol levels, and measures of depressive symptomatology and cognitive function will be obtained during the 2nd trimester, 3rd trimester, and 3 months post partum. This study will enable us to better understand immune-endocrine mechanisms of depression as well as disease activity in MS. This could have important implications for developing better therapeutic approaches.