Appropriate responsiveness to everyday-life stressors is crucial for adequate functioning in a natural environment. Conversely, depending on individual's genetic makeup, prolonged stress, coupled with inappropriate responsiveness may lead to physiological and psychiatric disorders. Various psychiatric conditions have been associated with stress and alterations in hypothalamic-pituitary-adrenal (HPA) activity. Yet while stress is a general phenomenon, illness is only seen in a proportion of individuals, suggesting genetic modifiers of ability to cope with stress. In children, relatively little research has been conducted to estimate the impact of genetic factors on the variability in HPA axis functioning.

In the present explorative investigation, 106 prepubertal children were studied to estimate the impact of four glucocorticoid receptor gene (NR3C1) polymorphisms (NR3C1-1, ER22/23EK, N363S, N766N) and five arginine vasopressin (AVP) receptor 1b gene (AVPR1b) polymorphisms (AVPR1b_s1, AVPR1b_s2, AVPR1b_s3, AVPR1b_s4, AVPR1b_s5) on cortisol responses after a psychosocial stress test (public speaking task).

ER22/23EK carriers displayed significant lower cortisol responses to psychosocial stress compared to noncarriers. This particular polymorphism has earlier been associated to the vulnerability to develop MDD by our own research group (1) and independently by another publication (2).

These findings support the relevance of the ER22/23EK polymorphism in HPA axis regulation and in the vulnerability for psychiatric disorders.

1. 1. van West D et al, Neuropsychopharmacology 31: 620-627, 2006.

2. 2. Van Rossum EFC et al., Biol Psychiatry 59: 681-688, 2006.