Animal models of human insomnia

Abstract

SummaryInsomnia disorder (chronic sleep continuity disturbance) is a debilitating condition affecting 5%–10% of the adult population worldwide. To date, researchers have attempted to model insomnia in animals through breeding strategies that create pathologically short‐sleeping individuals or with drugs and environmental contexts that directly impose sleeplessness. While these approaches have been invaluable for identifying insomnia susceptibility genes and mapping the neural networks that underpin sleep–wake regulation, they fail to capture concurrently several of the core clinical diagnostic features of insomnia disorder in humans, where sleep continuity disturbance is self‐perpetuating, occurs despite adequate sleep opportunity, and is often not accompanied by significant changes in sleep duration or architecture. In the present review, we discuss these issues and then outline ways animal models can be used to develop approaches that are more ecologically valid in their recapitulation of chronic insomnia's natural aetiology and pathophysiology. Conditioning of self‐generated sleep loss with these methods promises to create a better understanding of the neuroadaptations that maintain insomnia, including potentially within the infralimbic cortex, a substrate at the crossroads of threat habituation and sleep.

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).…”

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.…”

Insomnia – An outlook for the future

“…Beyond, we would like to suggest that research into the roles of histamine and noradrenaline may lead to new compounds with a positive effect on sleep (see van Someren, 2021). Therefore, animal models of insomnia need to be further refined in order to allow the investigation of multiple neurotransmitter systems related to ID (see Fernandez & Perlis, 2023). With respect to the pharmaceutical industry, we should insist that randomised place-controlled long-term studies should be conducted for any new substance (as it has already been done for daridorexant).…”