Clock gene influences on sleep quality and HPA axis in major depressive disorder

Abstract

Background: Major Depressive Disorder (MDD) has been associated with disruptions in circadian rhythms and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Circadian rhythms are regulated by clock genes, including BMAL1, which are also implicated in HPA axis function. This study aimed to examine the association between BMAL1 polymorphisms and sleep quality, their interactions with sex and MDD diagnosis, and their potential influence on HPA axis activity in MDD. Methods: The sample included 84 patients with MDD and 120 healthy controls (HCs). Clinical and sociodemographic variables were assessed. HPA axis activity was measured using the cortisol awakening response (CAR) and diurnal cortisol slope. Six single nucleotide polymorphisms (SNPs) in the BMAL1 gene were analyzed. Multiple regression models were used, adjusting for relevant covariates. Results: The BMAL1 SNP rs11022778 was significantly associated with sleep quality in the total sample. Interaction analyses revealed that this association was specific to individuals with MDD. Additionally, rs11022778 was significantly associated with both CAR and slope measures among MDD patients. Conclusions: These findings highlight the potential role of BMAL1 gene variants in modulating biological and clinical phenotypes related to circadian and stress regulation. The rs11022778 variant may contribute to altered sleep quality and HPA axis activity in MDD. Future research should consider such genetic markers to inform more personalized approaches to MDD treatment.