PER3 polymorphism and insomnia severity in alcohol dependence

Abstract

Study Objectives: Insomnia is common, persistent, and associated with relapse in alcohol-dependent (AD) patients. Although the underlying mechanisms are mostly unstudied, AD patients have impaired circadian rhythms and sleep drive, which may be genetically influenced. A polymorphism in the PER3 gene (PER3 4/4, PER3 4/5, PER3 5/5) has previously been associated with circadian preference and sleep homeostasis, and the PER3 4/4 genotype has been characterized by evening preference and decreased sleep drive. The purpose of this study was to examine the influence of this polymorphism on insomnia severity in AD patients. We hypothesized that the PER3 polymorphism would be an independent predictor of insomnia severity with greatest severity observed in those with the PER3 4/4 genotype. Design: Cross-sectional association of patient characteristics, genotype, and insomnia severity. Significant (P < 0.05) bivariate correlates were further analyzed by hierarchical, forced entry multiple linear regression. Setting: Alcohol treatment programs in Warsaw, Poland. Patients: Diagnosed with alcohol dependence (n = 285), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Measurements and Results: Drinking frequency, mental and physical health status, childhood abuse, and PER3 genotype were independent predictors of insomnia severity, as measured by a 7-item subscale of the Sleep Disorders Questionnaire, explaining 28.9% of the variance. Addition of the genotype in the final step significantly increased the amount of variance explained by 1.1% (P = 0.027). Those with the PER3 4/4 genotype had the greatest severity of insomnia symptoms. Conclusions: PER3 genotype contributed unique variance in predicting insomnia severity in AD patients. These results are consistent with genetically influenced impairment in sleep regulation mechanisms in AD patients with insomnia.