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Sleep Quality Varies as a Function of 5-HTTLPR Genotype and Stress

From the Department of Psychiatry and Behavioral Sciences (B.H.B., A.D.K., I.C.S., J.C.B., E.L.B., L.P.G., R.B.W.), Duke University Medical Center; Center for Human Genetics (A.A.-K.), Duke University Medical Center; Department of Pharmacology and Cancer Biology (C.M.K.), Duke University Medical Center; The Bryan Alzheimer's Disease Research Center (E.L.B., L.P.G.), Durham, North Carolina; and University of Miami Miller School of Medicine (S.Z.), Miami Institute of Human Genomics, Miami, Florida.

Address correspondence and reprint requests to Beverly H. Brummett, Box 2969 Duke University Medical Center, Durham, NC 27710. E-mail: brummett{at}duke.edu

Objective: To test the hypothesis that allelic variation in 5HTT gene-linked polymorphic region (5-HTTLPR) genotype was associated with sleep quality (Pittsburgh Sleep Quality Index, PSQI) as a main effect and as moderated by the chronic stress of caregiving. Serotonin (5HT) is involved in sleep regulation and the 5HT transporter (5HTT) regulates 5HT function. A common 44-base pair deletion (s allele) polymorphism in the 5-HTTLPR is associated with reduced 5HTT transcription efficiency and 5HT uptake in vitro.

Methods: Subjects were 142 adult primary caregivers for a spouse or parent with dementia and 146 noncaregiver controls. Subjects underwent genotyping and completed the PSQI.

Results: Variation in 5-HTTLPR genotype was not related to sleep quality as a main effect (p > .36). However, there was a caregiver X 5-HTTLPR interaction (p < .009), such that the s allele was associated with poorer sleep quality in caregivers as compared with controls.

Conclusions: Findings suggest that the s allele may moderate sleep disturbance in response to chronic stress.

Key Words: 5-HTTLPR • serotonin transporter promoter gene polymorphism • sleep quality • gene-environment interaction • stress

Abbreviations: 5HT = serotonin; 5-HTTLPR = 5HTT gene-linked polymorphic region; CSF = cerebrospinal fluid; 5HIAA = CSF levels of 5-hydroxyindoleacetic acid; PSQI = Pittsburgh Sleep Quality Index; SE = standard error.