DEPRESSION IN MS · Pathogenetic mechanisms of depression in multiple sclerosis
FP7 — People (Marie Curie Actions)
- Duration
- 2010-09-01 → 2014-08-31
- EU contribution
- €100,000
- Participants
- 1
- Scheme
- MC-IRG
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Results in brief
Periodic Report Summary - DEPRESSION IN MS (Pathogenetic mechanisms of depression in multiple sclerosis)
Summary description of the project objectives Pregnancy 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 project In 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 far In 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.
Data: CORDIS, © European Union
Project objective
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.
Original text from CORDIS.
Participants
- UNIVERSITAETSKLINIKUM HAMBURG-EPPENDORF · HamburgCoordinatorGermany
Links
Data: CORDIS, © European Union