Clinical and genetic associations of the CLOCK circadian rhythm gene and depressive disorders in patients with alcohol dependence syndrome during the period of alcohol abstinence

Abstract

About 20% of patients with depression are diagnosed with alcohol dependence, and alcohol dependent individuals are at a higher risk of developing depression. A number of authors point to the relationship of CLOCK gene activity with both affective disorders and alcohol use/dependence disorders; in particular, variations in the CLOCK gene at the evidence level link to depression and stress.Objective: to establish clinical and genetic associations of the CLOCK circadian rhythm gene and depressive disorders during the period of abstinence in patients with alcohol dependence syndrome.Patients and methods. From June 2019 to December 2022, 402 patients (mean age 42.47±7.5 years) were examined, who underwent outpatient follow-up at a narcological dispensary not earlier than 1 month after and not later than 2 months after discharge from the hospital. All patients were diagnosed with middle-stage alcohol dependence syndrome, early remission phase. Depending on the presence of an episode of depression at the time of the examination, the main group (patients with a depressive disorder; n=128) and a comparison group (patients without a depressive disorder; n=274) were formed. Clinical interviews and psychometric study using the Montgomery–Asberg Depression Scale, were conducted for all the subjects. All subjects provided 10 ml venous blood samples for molecular, genetic and biochemical studies.Results and discussion. Correlations were found between the carriage of the TT genotype of the CLOCK gene in patients with alcohol dependence and concomitant clinical depression. Carrying the TT genotype of the CLOCK gene is presumably associated with the predominance of the following symptoms of depression, which demonstrated statistically significant differences: loss of appetite, impaired concentration, apathy, as well as with a higher overall score on the MADRS depression scale. The established association between the CLOCK gene and depression in people with alcohol dependence can be considered as a vulnerability factor in relation to the development of depression in patients with the underlying disease – alcohol dependence syndrome.Conclusion. The CLOCK gene is associated with the development of depression in patients suffering from alcohol dependence. Carriers of the TT genotype of the CLOCK gene (rs1801260) to a greater extent than carriers of other genotypes are characterized by the development of comorbid depression, as well as the predominance of such clinical symptoms as loss of appetite, impaired concentration, apathy, and a higher overall score on the MADRS depression scale.

Keywords

• alcohol dependence syndrome
• alcohol withdrawal syndrome
• depression
• clock