Avaliação de alterações genéticas no eixo HPA na resposta a psicoterapias breves em pacientes com depressão maior

Abstract

Major depression (MD) is a common, recurrent and incapacitating psychiatric illness, of a multifactorial character whose etiology is still unknown. However, the interaction model between gene and environment, takes into account candidate genes for disease development, response to treatment, and psychosocial factors. As regards the pathogenesis of MD, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis seems to play an important role, through the release of corticotropin releasing hormones (CRH), adrenocorticotropic hormones (ACTH), and cortisol. Type 1 receptor in the CRH gene (CRHR1), the receptor for corticotropin releasing hormone (CRH) type 1 (CRHR1), has been associated with depressive and anxious symptoms, as well as response to antidepressant treatment. However, in addition to pharmacological treatment, models of brief psychotherapies have been shown to be effective in response of depressive symptoms and modulation of biological parameters. In this context, the objective of the present project was to investigate the association of the rs110402 SNP in the HPA axis CRHR1 gene with the severity of the depressive and anxious symptoms, as well as the response rates of these symptoms in patients with MD undergoing brief psychotherapy. This study is part of a randomized clinical trial comprised of individuals between 18 and 60 years of age who sought out the UCPel Outpatient Mental Health Research and Extension. At the entrance the individuals were diagnosed through the MINI Plus, they answered a socio-demographic questionnaire, and the biological material was collected. Patients diagnosed with DM were randomized to treatment with cognitive behavioral therapy (CBT) or supportive-expressive dynamic psychotherapy (SEDP), being evaluated in the pre- and post-treatment using the Beck Scale of Depression (BDI-II) scale for severity of depressive symptoms and Beck Anxiety Scale (BAI) for the severity of anxious symptoms. DNA was extracted from peripheral leukocytes and rs110402 polymorphism was genotyped by real-time PCR. Our study showed that genetic variation in the CRHR1 gene is not associated with the severity of depressive and anxious symptoms in patients with MD, however, rs110402 SNP genotypes in the CRHR1 gene may predict the response of psychotherapeutic treatment. Patients with the AA genotype had lower rates of response of the depressive and anxious symptoms in relation to those with the G allele.