Genetic variants and resilience to psychopathology

We screened human subjects for Single Nucleotide Polymorphism (SNPs) in the MR-gene and identified several new SNPs. Following the genotyping of several hundreds of human subjects we constructed haplotypes of the MR-gene. These haplotypes showed pronounced differences in a gene transactivation assay when cortisol was used as ligand. Following a psychosocial stressor (the Trier Social Stress Test) haplotype 3 associates with an increased cortisol and autonomic response. This indicates that common functional genetic variants in the MR-gene may have a strong impact on individual differences in stress-reactivity (DeRijk et al, 2005).

In different cohorts, we have gathered additional evidence for association of MR haplotypes with depression, bipolar disorder, and an important factor for resilience, optimism. These data indicate that in addition to GR also MR gene variants may modulate vulnerability to stress-related disorders.

These new genetic markers and stress-system challenge tests are being used as tools to further differentiate patient groups. Next, the environmental conditions under which common genetic makers determine vulnerability or resilience will be identified. In addition, the observed specific ligand – gene-variant interaction suggest an opportunity for individualized drug treatment.