Title:Early Life Stress in Depressive Patients: Role of Glucocorticoid and Mineralocorticoid Receptors and of Hypothalamic-Pituitary-Adrenal Axis Activity
Volume: 21
Issue: 11
Author(s): Mario Francisco Juruena, Cristiane Von Werne Baes, Itiana Castro Menezes and Frederico Guilherme Graeff
Affiliation:
Keywords:
Early life stress, depression, glucocorticoid receptor, mineralocorticoid receptor, hypothalamic-pituitary-adrenal axis.
Abstract: Depression is a chronic, recurrent and long-term disorder characterized by high rates of impairment and several
comorbidities. Early life stress (ELS) is associated with the increased risk for developing depression in adulthood, influences
its clinical course and predicts a poorer treatment outcome. Stressful life events play an important role in the pathogenesis
of depression, being well established as acute triggers of psychiatric illness. The vulnerability for developing depression
is associated to changes in neurobiological systems related to stress regulation. The hypothalamic-pituitaryadrenal
(HPA) axis responds to external and internal stimuli. Reported results indicate that stress in early phases of development
can induce persistent changes in the response of the HPA axis to stress in adulthood, leading to a raised susceptibility to depression.
These abnormalities appear to be related to the HPA axis deregulation in depression, partially due to an imbalance between glucocorticoid
receptors (GR) and mineral ocorticoid receptors (MR). While most studies have consistently demonstrated that GR function is
impaired in major depression (reduced GR-mediated feedback in HPA axis), data about the MR role in depression are still limited and
contr oversial. Thus, in this review article we summarize the main reported findings about the consequences of ELS in HPA axis functioning
and in the responsivity of MR/GR receptors in depression.