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

Abstract

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.

Dependent negative life events and sleep quality: An examination of gene–environment interplay

“…Despite a growth of research assessing GxE for a number of psychological and behavioural traits, there is a dearth of research focussing on GxE in relation to sleep quality. One study to date has found that a polymorphism of the serotonin gene (5HTTLPR) is associated with poor sleep quality, but specifically only in individuals experiencing chronic stress -conceptualised in the study as caregiving (19). What is unclear, however, is whether exposure to other negative life events has a modifying effect on the genetic and environmental factors influencing sleep.…”

“…From a quantitative genetic viewpoint, twin studies have demonstrated that genetic influences account for around 30-50% of the variance in several aspects of subjectively defined sleep (3)(4)(5)(6)(7)(8)(9)(10)(11). Moreover, molecular genetic studies have begun to identify DNA sequence variations related to sleep-wake behaviour (12)(13)(14)(15)(16)(17)(18)(19). While these studies demonstrate the genetic components of certain sleep phenotypes (traits), research has also highlighted the importance of investigating the role of lifestyle factors and environmental influences such as stressful and negative life events in the occurrence of sleep problems (19)(20)(21)(22)(23).…”

“…Moreover, molecular genetic studies have begun to identify DNA sequence variations related to sleep-wake behaviour (12)(13)(14)(15)(16)(17)(18)(19). While these studies demonstrate the genetic components of certain sleep phenotypes (traits), research has also highlighted the importance of investigating the role of lifestyle factors and environmental influences such as stressful and negative life events in the occurrence of sleep problems (19)(20)(21)(22)(23). A common conceptualisation of life events is to categorise them as dependent and independent, according to the controllability of such events (24).…”

Genotype-Dependent Differences in Sleep, Vigilance, and Response to Stimulants

“…It was speculated that reduced transcription associated with the S allele modulates serotonergic tone and 5-HT receptormediated neurotransmission [134]. Preliminary data indicate that the presence of the S allele affects subjective and objective measures of sleep in certain situations [135,136]. While the functional relationship between the genetic variation in SLC6A4 and sleep-wake regulation has not been studied in healthy individuals, it appears that homozygous depressed patients with the L/L genotype respond more favorably to therapeutic sleep deprivation than carriers of the S allele [137].…”

Anxiety Disorders and Sleep in Children and Adolescents

“…Indeed, interactions between genes and environmental factors are shown for difficulties including sleep quality [41] as well as various associated traits, including depression and behavioural difficulties (see [42] ).…”