D. Van West

A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression

Increasing amounts of data suggest that affective disorders might be related to dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, one of the stress-response systems. Arginine vasopressin (AVP) influences several symptoms, relevant to affective disorders, notable memory processes, pain sensitivity, synchronization of biological rhythms and the timing and quality of REM sleep. We examined whether genetic variations in the AVP receptor 1b gene (AVPR1b) could be associated with increased susceptibility to affective disorders using a gene-based association analysis of single-nucleotide polymorphisms (SNPs). Five SNPs were identified in AVPR1b and genotyped in two well-diagnosed samples of patients with recurrent major depression and matched controls. In the Swedish sample, we observed significant allele (P=0.02) and genotype (P=0.01) association with SNP AVPR1b-s3, and in the Belgian sample, a borderline significant association with SNP AVPR1b-s5 (P=0.04). In both patient–control samples, the haplotype defined by alleles A-T-C-A-G for the AVPR1b-s SNPs s1-s2-s3-s4-s5 was significantly over-represented in controls compared to patients. Our data support a protective effect of this major haplotype for recurrent major depression.

S63-04 Stress responsivity in childhood and adulthood: Role of the glucocorticoid receptor gene

Aims Prenatal stress has been associated with lifelong disturbances in stress response systems and with an increased vulnerability for psychiatric disorders. However, the effect of prenatal stress is at least partially determined by individual genetic makeup. Recent data confim the potential role of the glucocorticoid receptor (GR) gene in modulating stress response and in the liability to develop mood disorders. In genetic association studies, single nucleotide polymorphisms (SNPs) in the GR gene were linked to variation in stress response systems (1). In a preliminary investigation, we studied 106 prepubertal children to estimate the impact of four GR gene polymorphisms on cortisol responses after a psychosocial stress test. Results Carriers of the ER22/23EK mutation 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 (2) and independently by another publication (3). Conclusion These findings support the relevance of GR gene polymorphisms in general and of the ER22/23EK polymorphism in particular in HPA axis regulation and in the vulnerability for psychiatric disorders.