Polymorphisms in the gene encoding the neuropeptide galanin are associated with HPA-axis dysregulation and symptome severity in major-depressive- and anxiety-disorder patients

Galanin (GAL) is an estrogen inducible neuropeptide, highly expressed in brain-regions processing mood and behavior. GAL possibly has a direct modulatory effect on hypothalamic-pituitary-adrenal axis (HPA) regulation, as recent pharmacological and genetic studies indicate a significant role of GAL in stress-related disorders. By using a tag SNP approach covering the GAL-gene, we expanded an earlier finding of a genetic association with panic-disorder in female subjects to a larger sample of 268 outpatients with anxiety disorders (AD) and 541 inpatients with major depressive disorder (MDD). As intermediate phenotype for treatment response, HPA-axis dysregulation using the combined dexamethasone suppression/CRH stimulation test both at admission and discharge was evaluated in 298 MDD-inpatients. To test for case-control associations, a healthy control sample (n=541) was used. Genotyping revealed high LD in the promotor area of the GAL-gene, including predescribed estrogen binding element sites. We found associations of the rare allele of rs948854 in female AD-patients with more severe anxious pathology and in premenopausal MDD-patients with higher HPA-axis activity at admission, more severe anxious pathology at discharge and non-remission. No significant case-control associations could be observed. The here presented data suggest a gender-specific role of GAL SNPs in liability for anxious and depressive disorders, characterized by a particularly dysregulated HPA-axis.