Journal Club: October 5, 2012

Friday, October 5, 2012

Daniel Koffler (Tisch MS) presented the following article in Journal Club.

Article Title: Decreased Hydrocortisone Sensitivity of T Cell Function in Multiple Sclerosis Associated Major Depression

Reference: A. Fischer, C. Otte, T. Krieger, R. Nichols, S. Krüger, K. Ziegler, K. Schulz, C.Heesen, and S. Gold. (2012) Psychoneuroendocrinology. 37: 1712-1718.

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the CNS with a high prevalence of depression. Both MS and depression have been linked to elevated cortisol levels and inflammation, indicating disturbed endocrine-immune regulation. An imbalance in mineralocorticoid versus glucocorticoid signaling in the CNS has been proposed as a pathogenetic mechanism of depression. Intriguingly, both receptors are also expressed in lymphocytes, but their role for ‘escape’ of the immune system from endocrine control is unknown. Using steroid sensitivity of T cell function as a read-out system, the authors investigate a potential role of mineralocorticoid receptor (MR) versus glucocorticoid receptor (GR) regulation in the immune system as a biological mechanism underlying MS-associated major depression. Twelve female MS patients meeting diagnostic criteria for current major depressive disorder (MDD) were compared to twelve carefully matched MS patients without depression. The authors performed lymphocyte phenotyping by flow cytometry. In addition, steroid sensitivity of Tcell proliferation was tested using hydrocortisone as well as MR (aldosterone) and GR (dexamethasone) agonists. Sensitivity to hydrocortisone was decreased in T cells from depressed MS patients. Experiments with agonists suggested disturbed MR regulation, but intact GR function. Importantly, there were no differences in lymphocyte composition and frequency of T cell subsets, indicating that the differences in steroid sensitivity are unlikely to be secondary to shifts in the immune compartment. To the knowledge of the authors, this study provides first evidence for altered steroid sensitivity of T cells from MS patients with comorbid MDD possibly due to MR dysregulation.

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