Potential genetic and epigenetic mechanisms in insomnia: A systematic review

Abstract

SummaryInsomnia is a stress‐related sleep disorder conceptualised within a diathesis‐stress framework, which it is thought to result from predisposing factors interacting with precipitating stressful events that trigger the development of insomnia. Among predisposing factors genetics and epigenetics may play a role. A systematic review of the current evidence for the genetic and epigenetic basis of insomnia was conducted according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) system. A total of 24 studies were collected for twins and family heritability, 55 for genome‐wide association studies, 26 about candidate genes for insomnia, and eight for epigenetics. Data showed that insomnia is a complex polygenic stress‐related disorder, and it is likely to be caused by a synergy of genetic and environmental factors, with stress‐related sleep reactivity being the important trait. Even if few studies have been conducted to date on insomnia, epigenetics may be the framework to understand long‐lasting consequences of the interaction between genetic and environmental factors and effects of stress on the brain in insomnia. Interestingly, polygenic risk for insomnia has been causally linked to different mental and medical disorders. Probably, by treating insomnia it would be possible to intervene on the effect of stress on the brain and prevent some medical and mental conditions.

The pace of biological aging helps explain the association between insomnia and chronic low back pain

“…41 Other investigators have linked epigenetic age acceleration with chronic musculoskeletal pain such as knee osteoarthritis. [42][43][44] Given that DNA methylation alterations of stress-related inflammatory process correlate with cLBP 5,45,46 and insomnia, 47 it is possible that insufficient sleep quality that characterizes insomnia epigenetically induces inflammatory processes that accelerate aging, sustaining worse cLBP.…”

The European Insomnia Guideline: An update on the diagnosis and treatment of insomnia 2023

“…The patient reports, or the patient's parent or caregiver observes, one or more of the following: In this update we will not comment on aetiological and/or pathophysiological concepts of insomnia, as this would go far beyond the remit of this guideline. The interested reader is referred to recent work, much of which is part of the special insomnia issue of JSR (Dressle & Riemann, 2023;Espie, 2023;Fernandez & Perlis, 2023;Palagini et al, 2023;Reffi et al, 2023;Riemann et al, 2022;Tang et al, 2023;van Someren, 2021).…”

“…The authors report small to medium effects on sleep-related parameters in elderly T A B L E 1 3 Meta-analyses on the efficacy of sedating antidepressants in the treatment of insomnia patients and patients with insomnia, in short-term studies. Several very recent all-encompassing (network) meta-analyses included studies on fast-release, PR melatonin and ramelteon (De Crescenzo et al, 2022;Hasan et al, 2023;Maruani et al, 2023;Yue et al, 2023); however, the results are conflicting. Considering this evidence, fastrelease melatonin and ramelteon are not recommended for insomnia treatment (exception: if there are circadian factors involved) due to lack of efficacy.…”

Insomnia research: What have we learned and what else do we need to know?

“…For clinical purposes, we may need to rely more on practical assessment methods at the point of care. In addition, with the tremendous popularity of wearables and intelligent bracelets, insomnia research could be more informative by The papers on the genetics and epigenetics of insomnia (Palagini et al, 2023) and on animal models of human insomnia (Fernandez and Perlis, 2023) highlight some of the critical gaps in our understanding of the genesis and mechanisms of insomnia. Fernandez and Perlis outline very elegantly some of the problems with current animal models that use acute sleep deprivation as a proxy of insomnia and in doing so they fail to capture some of the core clinical features of chronic insomnia disorder.…”