Date of Award
Bachelor of Science
Depression, Genetics, HPA Axis, Mutation, Single Nucleotide Polymorphism
Depression is one of the most prevalent diseases worldwide, afflicting approximately 17 million adults in the US in 2019. A prominent causal factor of depression is dysregulation of our body’s response to stress when exposed to continuous stressors over long periods of time. Stress is regulated by the Hypothalamic-Pituitary-Adrenal (HPA) axis, with cortisol as its effector hormone. The effects of cortisol are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR, respectively) in the body and the brain, respectively. The HPA axis is regulated by a negative feedback loop where activation of the GR by circulating cortisol inhibits the production of additional cortisol.
Our lab investigated the role of single nucleotide polymorphisms (SNPs), or mutations, in the genes of the MR, GR, and associated regulatory proteins that are hypothesized to be involved in the dysregulation of function leading to hypersensitivity or resistance to cortisol in the HPA axis. Previous literature has demonstrated that prominent GR and MR SNPs correlate with higher incidence of depression and/or depressive symptoms. Our study continued this investigation into the relationship between mutations and depression in a clinical sample of psychiatric patients from Albany Medical College. We were especially interested in the interplay between mutations of the GR and MR influencing cortisol levels and response in our bodies. DNA from patients was collected with buccal swabs and genotypes were analyzed through allele specific and quantitative polymerase chain reactions. We compared genotypes to the Beck Depression Inventory (BDI) score of patients, as well as other scales measuring anxiety and mood. No significant two-tailed correlation between individual SNPs or GR/MR SNP combinations and BDI scores was found. One SNP in the GR gene (rs33389) and one SNP on the 11ß-hydroxysteroid dehydrogenase type 1 (rs12086634), an enzyme that regulates peripheral cortisol levels, demonstrated significant one-tailed correlations with the Mindful Attention Awareness Scale and State Trait Anxiety scale, respectively. Obtaining a greater sample size would yield more representation of mutant alleles and potentially allow for more significance correlating genetic mutations to the incidence of depression.
Bechu, Elsa and Cohen, Brian, "The Role of Single Nucleotide Polymorphisms Causing a Dysregulation of the HPA Axis on the Incidence of Depression" (2021). Honors Theses. 2531.