Corticosteroid receptor polymorphisms: Determinants of vulnerability and resilience

摘要: Why some individuals thrive and others break down under similar adverse conditions, is a central question in the neuroendocrinology of stress related psychopathology. The brain mineralocorticoid (MR) glucocorticoid receptors (GR) operate balance to coordinate behavioural, autonomic neuroendocrine response patterns involved homeostasis health. Genetic variants both MR GR have been functionally characterized. four GR-gene single nucleotide polymorphisms (SNPs) (ER22/23EK (allele frequency: 3%), N363S (4%), BclI (37%), A3669G (15%)) two MR-gene SNPs (-2 G/C (50%), MR-I180V (11%)) showed vitro changes transactivational capacity, or affect stability mRNA (GR exon 9beta A3669G). All these MR-and GR-SNPs change regulation hypothalamus-pituitary-adrenal (HPA) axis at different levels including basal level G/C), dexamethasone induced negative feedback (ER22/23EK, N363S, BclI, A3669G) following psychosocial test (Trier Social Stress Test (TSST); all GR-SNPs). Importantly, increased output enhanced cortisol secretion during TSST. Recently, several GR-variants found associated with psychopathology (depression, bipolar disorder). These data provide evidence that dysregulation are causative pathogenesis depression part genetic make up determines individual stress-responsivity coping style, affecting vulnerability disease.