History of maltreatment in childhood and adolescence and changes hypothalamic-pituitary-adrenal (HPA) axis in different subtypes of depression in adults patients

• Grant number: 10/20168-5
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2011
• End date: August 31, 2013
• Field of knowledge: Health Sciences - Medicine - Psychiatry
• Principal Investigator: Mario Francisco Pereira Juruena
• Grantee: Mario Francisco Pereira Juruena
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant(s): 11/50616-2 - Mineralocorticoid receptor polymorphism and function in patients with depression and early life stress, AP.R

Abstract

Increasing evidence indicates that abandonment, neglect and abuse in childhood and adolescence are risk factors for psychiatric disorders. Studies in both animals and humans suggest that stress in the early stages of development may induce persistent changes in the ability of the hypothalamic-pituitary-adrenal (HPA) in response to stress in adult life leading to greater susceptibility to depression. The hyperactivity of the HPA axis, characterized by a hyperactivation of CRH (Corticotropic Release Hormone), reduced negative feedback and hypercortisolism has been a constant finding in major depression. These abnormalities seem to be related to changes in the ability of circulating glucocorticoids to exert their negative feedback on secretion of hormones of the HPA axis by binding to mineralocorticoid receptors (MR) and glucocorticoid (GR) in HPA tissues. However, given the wide variety of stressors, as well as the different subtypes of depression, the findings of current studies have been inconsistent, therefore, become necessary for further studies that may elucidate the mechanisms underlying the link between maltreatment childhood and the development of depressive psychopathology in life adulta. O central role of MR for the regulation of HPA genotype variant MR I180V SNP is associated with increased cortisol has a specific effect on depressive symptoms, regardless of cognitive function. Recently, it was discovered that the MR I180V polymorphism carriers had higher scores of depressive symptoms than non-carriers. The aim of this study is to assess the association between maltreatment (physical abuse, sexual, neglect, or stress early) childhood and specific alterations of the HPA axis and the function of GR and MR receptors in different subtypes of depression. Methodology: To be recruited three groups: one group of patients with a history of childhood maltreatment and/or neglect and/or early life stress and current diagnosis of depressive episode, a group of patients without a history for child maltreatment and/or neglect and/or stress early diagnosis and current depressive episode and a group of healthy controls. Patients will be assessed by the Structured Clinical Interview for Disorders of Axis I DSM-IV (SCID-I) for the diagnosis of depression, to assess the severity of the condition are used Depression Rating Scale and Hamilton Depression Inventory Beck II. Is also used the Beck Anxiety Inventory, the Beck Suicide Inventory and Beck Hopelessness Scale. The presence of a history of abuse, neglect and abuse in childhood will be confirmed through the application of the Childhood Trauma Questionnaire (QUESI). The study will be placebo controlled, blinded by the controls and patients not randomized design with repeated measures used previously, where the effects of steroids as Fludrocortisone (0.5 mg), prednisolone (5 mg), dexamethasone (0.5 mg ) and Spironolactone (200mg) will be evaluated in salivary cortisol in patients and in healthy controls. This is a protocol of 10 days, followed by the medications and placebo plus a 2-day interval between administration of a drug and another. The secretion of salivary cortisol will be evaluated to awaken in all subjects, after having taken the day before to 22h: a placebo capsule, Fludrocortisone, prednisolone, dexamethasone and spironolactone. The salivary cortisol will be collected upon awakening, 30 and 60 minutes in the following days after the challenges. Plasma and saliva samples will be collected after an overnight fast each day after administration of fludrocortisone, prednisolone, dexamethasone and spironolactone. to measure the plasma and salivary cortisol, ACTH, AVP, aldosterone, DHEA-S. (AU)