Periodic Report Summary - DEPRESSION IN MS (Pathogenetic mechanisms of depression in multiple sclerosis) Summary description of the project objectivesPregnancy has a profound effect on disease activity in multiple sclerosis (MS), an inflammatory and demyelinating disease of the central nervous system (CNS). During pregnancy, the risk for developing disease relapses is dramatically reduced while the risk for exacerbations increases in the post partum period. In addition, pregnancy and the post partum period are often accompanied by the occurrence of depressive symptoms, a common symptom of MS. The biological mechanisms underlying the risk for MS relapses and depression during this time, however, are poorly understood. The purpose of the current longitudinal clinical study is to investigate the role of immune and endocrine mechanisms for MS exacerbations and depression during pregnancy. To study this, we are conducting a longitudinal study combining clinical assessments with laboratory analyses of immune function and hormone secretion in women with MS during pregnancy (first, second and third trimester) as well as three months post partum.Description of the work performed since the beginning of the projectIn the first two years since the start of the project, we have set up an interdisciplinary research group at the Institute for Neuroimmunology and Clinical Multiple Sclerosis Research (inims), Center for Molecular Neurobiology and Department of Neurology, University Hospital Hamburg-Eppendorf, Germany. We have currently enrolled 16 pregnant MS patients in the study. Laboratory analyses are ongoing.Description of the main results achieved so farIn the first subjects who have completed the study so far (n = 5), we have found a significant increase of a regulatory subset of natural killer (NK) cells with a corresponding decrease in cytotoxic NK cells during pregnancy. No shifts so far have been observed in T cell phenotype.Expected final results and their potential impact and use From this project, we expect novel insights into endocrine-immune cross talk during pregnancy that will advance our understanding of mechanisms underlying disease activity in MS. This may offer novel therapeutic targets for preventing potentially relapse-triggering events (i.e. markers that are upregulated in the relapse-prone post partum period). In addition, this 'learning from nature' approach could identify potentially protective pathways that help achieve disease quiescence seen in MS during pregnancy which may then be targeted pharmacologically. Furthermore, examining depression and its neuroimmune and endocrine correlates during pregnancy in MS will provide important insights into the biological mechanisms and help to develop much needed targeted therapies for depression in MS as well as likely by extension for pregnancy-associated depression in patients with other autoimmune diseases and possibly healthy women.