In 2020, the World Health Organization reported over 264 million people across the world were suffering from depression. Studies have demonstrated that one source of depression is a hormonal imbalance involved in the stress response. Cortisol is a stress hormone regulated by the Hypothalamic-Anterior-Pituitary (HPA) Axis. Its effects on the stress response and other metabolic activities in the body are exerted through the glucocorticoid and mineralocorticoid receptors (GR and MR respectively).
Our research has examined mutations known as single-nucleotide-polymorphisms (SNPs) relating to cortisol-receptor sensitivity and the behavior of cortisol in the body to investigate the link between cortisol activity and depression. The relationship between SNPs relating to receptor sensitivity and depression in patients will be established by analysis of SNPs in coordination with data from psychological inventory assessments collected for each patient. Patient samples and clinical information was collected from adult patients diagnosed with depression by collaborating physicians. Quantitative polymerase chain reaction (qPCR) was used for genotyping. Analysis of the data yielded no significant correlation between SNPs relating to GR or MR and depression as scored by the Beck Depression Inventory (BDI). However one SNP in GR (rs33389) and one SNP on the 11ß-hydroxysteroid dehydrogenase type 1 gene (rs12086634) correlated with scores on the Mindful Attention Awareness Scale and State Trait Anxiety scale, respectively.
Current studies focus on SNPs involved in the regulation of GR and MR activity that are not directly found in those receptors such as the FKBP5 GR co-regulator protein. Investigating other non-GR and MR SNPs could provide alternate explanations for cortisol sensitivity beyond the receptors themselves. In analyzing genetic differences relating to cortisol sensitivity in patients clinically diagnosed with depression, we aim to determine if an imbalance in an individual’s response to cortisol is linked to depression. If such a relationship can be established, this can provide physicians with a screening tool to better inform them of a patient’s risk factors for depression.