An evolutionary-emotional perspective of insomnia and parasomnias Lampros Perogamvros a, b, c a Center for Sleep Medicine, Department of Medical Specialties, Geneva University Hospitals, Geneva, Switzerland b Department of Neuroscience, Faculty of Medicine, University of Geneva, Geneva, Switzerland c Swiss Center for Affective Sciences, University of Geneva, Geneva, Switzerland Corresponding author: Lampros Perogamvros, MD Department of Medical Specialties (Geneva University Hospitals) and Department of Neuroscience (University of Geneva) Chemin des Mines 9, 1202 Geneva, Switzerland [email protected] 1 Summary Based on past literature, it is here supported that insomnia, and parasomnias such as sleepwalking, sleep terrors and nightmares, reflect an evolutionary survival mechanism, which has threat-related origins and which, in some vulnerable individuals, becomes persistent due to failure of a fear extinction function. Genetic determinants, personality traits and sleep disturbances seem to determine whether the individual will resume normal sleep after the acute phase (return to safety) or will develop the pathological condition of chronic insomnia, persistent sleepwalking in adulthood and nightmare disorder. Possible treatments targeting fear extinction are proposed, such as pharmacotherapy, cognitive behavioral therapy and targeted memory reactivation during sleep. Keywords: insomnia, sleepwalking, nightmares, evolution, fear extinction Abbreviations: 2 ACC: anterior cingulate cortex CB1: cannabinoid receptor type 1 CBT : cognitive behavioral therapy CBT-I: cognitive behavioral therapy for insomnia CR: conditioned response CS: conditioned stimulus DSM5: Diagnostic and Statistical Manual of Mental Disorders- Fifth edition fMRI: functional magnetic resonance imaging HEP: heartbeat evoked potential ICSD3: International Classification of Sleep Disorders - Third Edition mPFC: medial prefrontal cortex N2:stage 2 of NREM sleep N3: stage 3 of NREM sleep NREM: non-rapid eye movement sleep PTSD: post-traumatic stress disorder REM: rapid eye movement sleep THC: tetrahydrocannabinol TMR: targeted memory reactivation TST: threat simulation theory US: unconditioned stimulus Introduction 3 The pathophysiology of insomnia and parasomnias remains poorly understood. The presence of an external or internal stressor has been associated with the appearance of acute insomnia (1), nightmares (2), sleepwalking and sleep terrors (3). However, the factors accounting for the transition between the transient appearance of such disorders (usually few weeks) to a more persistent phase (usually many months or years) are not well understood. According to DSM-5 (4), there are clear specifiers for the duration of insomnia disorder and nightmare disorder. For insomnia, the acute phase is defined as having a duration ≤1 month and the chronic phase, as persistence of insomnia for ≥3 months (4). For nightmares, the acute phase is defined as having a duration ≤1 month and the persistent phase, as the persistence of nightmares for ≥6 months (4). On the other hand, for disorders of arousal (NREM parasomnias), apart from the notion of recurrence of episodes, there are no clear duration specifiers in DSM-5 or ICSD-3. NREM parasomnias most often occur initially in childhood and decrease in occurrence until young adulthood. However, they may endure in adulthood, which characterizes a persistent form. The prevalence of chronic insomnia, persistent nightmares and adult sleepwalking is 10-20% (5) , 4% (6) and 2% (3), respectively. Longitudinal or natural history studies are rather scarce in both insomnia (7) and parasomnia disorders (8), which could be of considerable help for understanding the nature of main determinants for the transition between transient and persistent phases of these disorders. Genetic factors have been attributed to insomnia (9), sleepwalking (10) and nightmares (11). Personality traits, which are largely genetically determined (12), have also been linked with insomnia (13), sleepwalking and nightmares (14). However, the specific role of genetic determinants, personality traits and stressful environmental events in the etiology of insomnia and NREM parasomnias is not yet clear. 4 Several theories have tried to explain how acute insomnia can develop into chronic insomnia (15, 16). Most models support that behaviors and cognitions adopted by the individual to cope with acute insomnia, actually reinforce the problem and produce chronic insomnia, mainly by instrumental conditioning (17). A similar approach, of learned dysfunctional behaviors and cognitions, has also been followed for chronic nightmares (18). No such hypothesis has been given for sleepwalking or sleep terrors, perhaps because these disorders seem to decrease spontaneously in frequency and intensity during the transition between childhood and adulthood. Recently, several different authors have suggested that the aforementioned sleep disorders may have served a survival function in our ancestral past (1, 19-21). At least for insomnia and sleepwalking, this function may have become unnecessary in post-industrial society, due to radical improvements in environmental safety. However, the threat-related origin of acute insomnia and parasomnias seems universal and intertemporal, although different in character between our ancestral past and the present. In this review, this idea of the evolutionary function of insomnia and parasomnias will be further developed, by proposing a common survival mechanism underlying the origin of these disorders. An adaptive response to real or perceived stress characterizes the transient phase of insomnia and parasomnias, whereas the failure of fear extinction and of return to safety would account for their persistent phase. Specific factors would determine which individuals would return to normal sleep and who would develop a chronic sleep disorder. According to this perspective, targeting dysfunctional fear memories would be important for a successful treatment of these sleep disorders. The evolutionary function of insomnias and parasomnias 5 According to the evolutionary mismatch hypothesis, specific traits that were once advantageous for human survival, became maladaptive due to changes in the environment (22). In the following paragraphs, a mismatch hypothesis will be formulated for insomnia and parasomnias. It will be supported that insomnias and most parasomnias reflect an adaptive response to real or perceived stress, and that an evolutionary mismatch rendered these disorders rather dysfunctional in modern society (as compared to our ancestral past). Threat- related experiences seem to be at the origin of the acute forms of these phenomena in both the distant past and present of human history, while failure to extinguish the real or perceived threat would account, at least partly, for their persistence over time. The evolutionary function of insomnia Several authors have implied that acute insomnia is part of the normal stress response while encountering a danger in the environment. Spielman and Glovinsky state “No matter how important sleep may be, it was adaptively deferred when the mountain lion entered the cave”(23). For McNamara and Auerbach, insomnia is also an adaptive response to a perceived or real threat (24). Similarly, Ellis et al. suggested that acute insomnia is a normal biopsychosocial response to a perceived or actual stressor (1). Empirical evidence for this hypothesis comes from a recent study in Hadza hunter-gatherers of Tanzania, which shows that a chronotype variation and the resulting asynchrony in activity levels allow one or more individuals to stay awake during the night, which may serve a need for survival and protection from environmental dangers (25). As in modern western societies, such a danger (from wild animals, hostile tribes etc) is not an issue anymore, individuals should normally have continuous sleep without any need for hypervigilance. However, in dangerous neighborhoods in developed or developing countries (26) or under war conditions in both Western and non- 6 Western countries, such a behavior is found commonly (27), and it seems to chronically characterize war veterans as well (28). Further evidence for this adaptive function of insomnia comes from electroencephalographic and cognitive studies, demonstrating a neurophysiological (cortical) and cognitive hyperarousal in these subjects, with milder cognitive costs and sleepiness in insomnia, as compared to sleep deprivation (29), even in those cases associated with significant objective short sleep duration (30). Most stressors causing acute insomnia in modern society are very different in nature than in physical threats, thus making us question what the benefit of losing sleep for them is. Anxiety about an exam or after a marital separation can cause insomnia, but these conditions are hardly comparable to being vigilant for predators or dangers. According to the mismatch hypothesis, initially adaptive solutions from our ancestral past and their modern ‘homologues’, would automatically activate the same ‘fight or flight’ systems. Interestingly, sleep duration correlates negatively with predation risk, foraging and social interactions (31), implying that ecology, and not functional benefits of sleep, is the primary driver of sleep duration (20). This could mean that insomnia, either acute or chronic, would still reflect an ecological pressure nowadays. In this perspective, acute insomnia would be a result of a natural process signaling to the person