Depression is associated with hypothalamic-pituitary-adreno cortical (HPA) hyperactivity and remission occurs with normalisation of this system. This, say researchers in the USA, China and Europe, raises the possibility that genes regulating HPA activity might influence the response to antidepressant treatment (Arch Gen Psychiatry 2010;67:369-79).

They used DNA from participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial of citalopram to study variants of the genes regulating corticotropin-releasing hormone and arginine vasopressin systems. One single-nucleotide polymorphism was statistically associated with remission and symptom improvement. This variant was associated with glucocorticoid receptor resistance and higher HPA-axis hormone levels. However, it occurred only in Hispanic and African American people and mainly for those with anxiety and depression. There was no association in participants of European origin, who constituted about two-thirds of the patients.

Coincidentally, a randomised double-blind trial recently evaluated the efficacy of a cortico­trophin-releasing factor receptor antagonist, pexacerfont, in the treatment of generalised anxiety disorder (Depression and Anxiety 2010;27:417-25). Surprisingly, in view of encouraging findings in animal models, pexacerfont 100mg daily was not superior to placebo in reducing Hamilton Anxiety Scale total score after eight weeks’ treatment whereas escitalopram 20mg daily was clearly beneficial. Response rates were 42, 42 and 53 per cent with pexacerfont, placebo and escitalopram respectively.