Early Life Stress in Depressive Patients: HPA Axis Response to GR and MR Agonist.
BACKGROUND
Evidence indicates that early life stress (ELS) can induce persistent changes in the hypothalamic-pituitary-adrenal (HPA) axis to respond to stress in the adult life that leads to depression. These appear to be related to the impairment of HPA hormones through binding to glucocorticoid (GR) and mineralocorticoid receptors (MR). The aim of this study was to evaluate the impact of ELS in HPA axis response to challenges with GR and MR agonists in depressed patients.


METHODS
We included 30 subjects, 20 patients with current major depression (HAM-D21 ≥ 17). Patients were recruited into two groups according to ELS history assessed by the Childhood Trauma Questionnaire (CTQ). The cortisol measures in the saliva and plasma were evaluated after using (at 10:00 p.m.) placebo, fludrocortisone (MR agonist), or dexamethasone (GR agonist).


RESULTS
Depressed patients showed a significantly lower salivary cortisol upon waking after placebo compared with controls. Moreover, cortisol awakening responses (CAR) after MR agonist were found to be lower in depressed patients than in controls. With CTQ scores, HAM-D21, body mass index and CAR after placebo, GR agonist, MR agonist we found in a Linear Regression model that depressive patients with ELS (p = 0.028) show differences between placebo vs. MR agonist (R = 0.51; p < 0.05) but not after GR agonist; in depressive patients, without ELS the data show differences between placebo vs. MR agonist (R = 0.69; p < 0.05); but now as well placebo vs. GR agonist (R = 0.53; p < 0.05).


CONCLUSIONS
Our findings indicate that MR activity is impaired in depressed patients compared with controls. Furthermore, in spite of the previous limitations described, in depressed patients with ELS, there was suppression by MR agonist, indicating that patients with ELS are sensitive to MR agonists. In contrast with depressed patients without ELS, we find suppression after both MR and GR agonist. These data suggested that in ELS an imbalance exists between MR and GR with MR dysfunction.
Stress and Affective Disorders - SAD Program, Mental Health Graduate Program, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil.
Cristiane von Werne
Cv
Baes
Stress and Affective Disorders - SAD Program, Mental Health Graduate Program, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil.
Camila Maria Severi
CM
Martins
Stress and Affective Disorders - SAD Program, Mental Health Graduate Program, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil.
Sandra Márcia de Carvalho
SM
Tofoli
Stress and Affective Disorders - SAD Program, Mental Health Graduate Program, Department of Neuroscience and Behaviour, Faculty of Medicine of Ribeirão Preto, University of São Paulo , São Paulo , Brazil ; Institute of Psychiatry, King's College London , London , UK.
Mário Francisco
MF
Juruena
cortisol; depression; early life stress; glucocorticoid receptors; hypothalamic-pituitary-adrenal; mineralocorticoid receptors