CRH1- and GR-gene SNPs and haplotypes: Associations with response to Dex/CRH test and antidepressant treatment?

Hormones of the HPA system and their receptors, especially CRH₁ receptors and GR, which are highly polymorphic in humans, are involved in the pathophysiology and treatment of depression. Multiple functional variants might contribute to the broad interindividual variation of the set point of the HPA system activity in depression and response to treatment.

We investigated 133 consecutively admitted inpatients with unipolar major depression. 100 of these patients received standardized treatment with either mirtazapine or citalopram for 5 weeks. The Dex/CRH test was administered at the beginning, and in case of standardization, at the end of antidepressant treatment. 4 SNPs in the CRH₁ gene and 3 SNPs in the GR gene were assessed. Haplotypes were estimated using an EM-algorithm. We tested for associations between variants of SNPs and haplotypes of both genes with the hormonal response to the Dex/CRH test, the response to antidepressant treatment (HAMD) and neuropsychological measures. Preliminary analysis demonstrates associations of CRH₁ gene variants and changes in HAMD scores and HPA function during standardized treatment.