Stress impairs response to antidepressants via HPA axis and immune system activation.

This study aims to disentangle this interaction by investigating the effects on two of the main stress-response systems of the body, the hypothalamic-pituitary-adrenal (HPA-) axis and the immune system in depressed patients. The function of the HPA-axis was assessed by measuring FKBP5, SGK1 and NR3C1 mRNA-expression in peripheral blood after an in vivo glucocorticoid receptor (GR) challenge with 1.5mg dexamethasone in 150 depressed in-patients (47.4% females). Childhood trauma was evaluated using the Childhood Trauma Questionnaire (CTQ), severe life events occurring one year prior to hospital admission were assessed with the List of Threatening Experiences (LTE). Multiple childhood traumata, i.e. ≥ 3, were present in 68 (45.5%) patients, 59 (39.3%) experienced ≥ 3 severe recent life events. The history of ≥ 3 severe recent life events was associated with an impaired GR-induction of SGK1 (F=10.455; df=1; p=0.002) and FKBP5 mRNA expression (F=8.720; df=1; p=0.004), and with elevated measures of the immune system such as CRP and lymphocyte count. In addition, severe recent life events were associated with a substantially impaired treatment response to antidepressants (F=7.456; df=1; p=0.008). These effects could not be observed in relation to childhood trauma. Severe life events occurring prior to MDD development substantially impaired the stress-response systems and the response to treatment with antidepressants. This finding may indicate the need to employ additional tre...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research