Treatment of depression is associated with suppression of nonspecific and antigen-specific TH1 responses in multiple sclerosis

Objective: To examine the relationship between depression, treatment of depression, and interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells in patients with comorbid diagnoses of relapsing-remitting multiple sclerosis (MS) and major depressive disorder. Design: A randomized comparative outcome trial of three 16-week treatments for depression. Assessments were conducted at baseline, week 8, and treatment cessation. Setting: An academic outpatient treatment and clinical research center. Patients: Fourteen patients who met the criteria for relapsing-remitting MS and major depressive disorder. Interventions: Individual cognitive behavioral therapy, group psychotherapy, or sertraline therapy. Main Outcome Measures: Depression was assessed using the Beck Depression Inventory. Interferon gamma production by peripheral blood mononuclear cells was measured following stimulation with OKT3 or recombinant human myelin oligodendrocyte glycoprotein (MOG). Variability in immune assays was controlled using 8 nondepressed healthy subjects who were enrolled at times corresponding with the enrollment of MS patients. Results: Results of the Beck Depression Inventory were significantly related to IFN-gamma production stimulated with OKT3 or MOG at baseline (P less than or equal to .03 for all). Level of depression, OKT3-stimulated IFN-gamma production, and MOG-stimulated IFN-gamma production all declined significantly over the 16-week treatment period (P less than or equal to .03 for all). Among controls, there were no significant changes over time in OKT3-or MOG-stimulated IFN-gamma, or in depression (P greater than or equal to .25 for all). Conclusions: These findings suggest that the production of the proinflammatory cytokine IFN-gamma by autoaggressive T cells in relapsing-remitting MS is related to depression and that treatment of depression may decrease IFN-gamma production. Thus, treatment of depression may provide a novel disease-modifying therapeutic strategy as well as a symptomatic treatment for patients with MS.