Anxious depression is a common subtype of major depressive disorder (MDD) and is associated with greater severity and poorer outcome. Alterations of the hypothalamic-pituitary-adrenal (HPA) axis, especially of the glucocorticoid receptor (GR) function, are often observed in MDD, but evidence lacks for anxious depression. Childhood adversity is known to influence both the HPA axis and risk of MDD. Therefore, we investigated GR-function in anxious depression dependent on childhood adversity.

We enrolled 144 depressed in-patients (49.3% females). Anxious depression was defined using the Hamilton Depression Rating Scale (HAM-D) anxiety/somatization factor score ≥7. Blood draws were performed at 6 pm before and 3 h after 1.5 mg dexamethasone ingestion for measurement of cortisol, ACTH and blood count to assess GR-function and the immune system. In a subgroup of n = 60 FKBP5 mRNA controlled for FKBP5 genotype was measured before and after dexamethasone. Childhood adversity was evaluated using the Childhood Trauma Questionnaire (CTQ).

We identified 78 patients (54.2%) with anxious depression who showed a greater severity and worse outcome. These patients were more often exposed to sexual abuse (30% vs. 16%/p = 0.04) and emotional neglect (76% vs. 58%/p = 0.02) than patients with non-anxious depression. Anxious depressed patients showed an enhanced GR-induced FKBP5 mRNA expression (F = 5.128; p = 0.03) and reduced cortisol levels, partly dependent on sexual abuse (F = 7.730; p = 0.006). Additionally, the GR-induced leukocyte response was enhanced in patients with sexual abuse (F = 7.176; p = 0.008).

Anxious depression in dependence of childhood trauma is associated with heightened sensitivity of the HPA axis and the immune system which should be considered for treatment algorithms and targets.