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Sleep patterns, frequently altered in depression, have been hypothesized to be under genetic control. The circadian locomotor output cycles kaput (CLOCK) T3111C variant has been studied in association with sleep disturbances in depressed patients. The aim of this study was to investigate possible effects of T3111C CLOCK on insomnia, daytime sleepiness, sleep quality, and depression severity in a sample of 100 major depressive disorder patients. Inclusion criteria were: major depressive disorder, drug-free for any antidepressant and/or benzodiazepines for at least four weeks previously to the study, and a minimum score of >17 on the Hamilton Rating Scale for Depression. The Morningness-Eveningness Questionnaire, Epworth Sleepiness Scale, Athens Insomnia Scale, and Pittsburgh Sleep Quality Index were applied. No significant difference was found concerning genotype or allele groups and Hamilton Rating Scale for Depression items or clusters. No difference was found between genotypes and comorbidity, chronotype distribution, Epworth Sleepiness Scale, Athens Insomnia Scale, or Pittsburgh Sleep Quality Index total scores. Overall, the present findings did not support the hypothesis of an effect of the T3111C CLOCK variant on sleep disturbances in major depressive disorder. Further analysis of clock machinery will clarify the contribution of clock genes to the maintenance of mental health.

It has been hypothesized that abnormalities in the molecular clock underlie the development of mood disorders, in the direction of higher prevalence in individuals with a reduced flexibility to adapt to important regulations of mood in response to changes in seasons, stress levels, sleep schedules, and time zones. In particular, a T/C change (rs1801260) at the 3111 position of the circadian locomotor output cycles kaput (CLOCK) gene has been explored in psychiatry disorders. This meta-analysis has been undertaken to investigate the association between rs1801260 and both mood disorders and depression severity, shedding light on previous controversial results and providing better power to detect smaller effect sizes. PubMed and ISI databases were searched for studies focused on the association between rs1801260 and mood disorders spectrum. Quality of studies was assessed. We found no association between CLOCK genotypes and mood disorders, even when we separately investigated ethnical homogeneous or unipolar disorder studies. No association was found regarding severity of depression either. The methodological quality of the studies has been found to be medium-high. Our meta-analysis shows no association between rs1801260 and mood disorders (as a complete phenotype) or depression severity and points out the necessity of further research in order to better understand the underlying biological machinery of circadian dysfunction in subjects affected by mood disorders.

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