Depression, Genes, Cytokines, Chronic Fatigue, Physical Illnesses and Quality of Life

Overview

Depression is one of the most common psychiatric diseases, with prevalence estimates ranging from 5% to 20%. Depression is now recognized as a brain disease; it can be managed and treated effectively with a wide range of options, but its biological basis is still far from clear. Studies of monozygotic and dizygotic twin pairs suggest polygenic inheritance, with an overall heritability estimate between 40% and 70 %. Gene-environment interaction has been recognized for a long time in the pathophysiology of depression, and its best biological substratum at present is represented by the serotonin transporter (5-HTT) gene. It would be interesting to study association between the novel allelic variants or at least the triallelic 5-HTTLPR polymorphism and depression. Depression is common in patients with end-stage renal disease and to occur in about 20% to 30% of hemodialysis patients. Interferon-induced depression is estimated up to 50% among patients with hepatitis C. Several sets of observations support the supposition that cytokines, and proinflammatory cytokines in particular, are involved in depressive disorders. Depression sufferers have been reported to have elevated blood levels of interleukin 1 (IL-1), IL-6 and tumor necrosis factor α (TNF-α).

The aim of this study is to examine the relations between depression and psychiatric family history, candidate genes, cytokines and health-related quality of life among hemodialysis patients and patients receiving interferon treatment for hepatitis C. The investigators aim to recruit 200 hemodialysis patients and 100 patients receiving interferon treatment for hepatitis C at Chang Gung Memorial Hospital, Keelung. Our pilot study found that among hemodialysis patients, the prevalence rates of probable anxiety disorder and probably depression disorder was 25.9% and 40.0%. Among the patients receiving interferon treatment for hepatitis C, the prevalence rates of probable anxiety disorder and probably depression disorder was 30.2% and 20.7% at baseline, and 44.0% and 36.2% at 3 months after interferon treatment. The study procedure consists of 2 parts. For the first one, all the recruited hemodialysis patients will receive assessments for fatigue symptoms using Fatigue Scale, depressive symptoms using Hospital Anxiety and Depression Scale (HADS) and Montgomery Asberg Depression Rating Scale (MADRS), Short-form Health-related Quality of Life (SF-36), blood levels of IL-1β, IL-6 and TNF-αas well as psychiatric diagnostic interview with the Mini-International Neuropsychiatric Interview (MINI) and the Family Interview for Genetic Study (FIGS). The second one is a prospective follow up of patients receiving interferon treatment. Before initiating interferon treatment, the subjects will receive baseline assessments using the same scales mentioned above. The investigators will genotype the 5-HTTLPR triallelic polymorphism on all subjects. The follow-up visits are at month 1, month 3, termination, and one month after termination of interferon program. This proposed project will provide a broad view and better understanding of the gene-environment interaction in the etiology of depression.