Relationship Between Single Nucleotide Polymorphisms and Dysregulation of the HPA-axis in Predisposition to Depression

There is currently a gap between what is known about genetic susceptibility to depression and how the condition presents itself. It is known that individuals with diseases that cause too much or too little of the stress hormone cortisol, are typically diagnosed with depression. This led our lab and others to the hypothesis that genetic factors related to cortisol action may put someone at an increased risk for developing depression. We used allele specific PCR to study the frequency of single nucleotide polymorphisms in genes associated with the function of different components of the hypothalamic-pituitary-adrenocortical axis (HPA-axis) to determine if dysregulation is associated with increased risk. Additionally, saliva samples were taken to quantify cortisol levels. Thus far, we have found significant relationships between the glucocorticoid receptor (GR) SNPs rs41423247 and rs56149945 and scores on the Beck Depression Inventory. The GR SNP rs10052957 and the mineralocorticoid receptor SNP rs5522 showed significant relationships with the State and Trait Anxiety Inventory. We have also found that SNPs rs12086634 and rs5522 may be related to increased risk. In addition to these SNPs we are currently investigating over ten others. Understanding how these changes in the HPA axis relate to altered function may be an important part of determining how to better diagnose and treat depression. Through the use of genomic data, this research could provide the means to improve current treatments of depression and be the next step to personalized clinical care.