While sleep serves important regulatory functions for mental health, sleep disturbances, in particular insomnia, may favour a state of allostatic overload impairing brain neuroplasticity and stress immune pathways, hence contributing to mental disorders. In this framework, the aim of this work was to link current understanding about insomnia mechanisms with current knowledge about mental health dysregulatory mechanisms. The focus of the present work was on mood, anxiety, and psychotic disorders, which represent important challenges in clinical practice. Literature searches were conducted on clinical, neurobiological, and therapeutic implications for insomnia comorbid with these mental disorders. Given the complexity and heterogeneity of the existing literature, we ended up with a narrative review. Insomnia may play an important role as a risk factor, a comorbid condition and transdiagnostic symptom for many mental disorders including mood/anxiety disorders and schizophrenia. Insomnia may also play a role as a marker of disrupted neuroplasticity contributing to dysregulation of different neurobiological mechanisms involved in these different mental conditions. In this framework, insomnia treatment may not only foster normal sleep processes but also the stress system, neuroinflammation and brain plasticity. Insomnia treatment may play an important preventive and neuroprotective role with cognitive behavioural therapy for insomnia being the treatment with important new evidence of efficacy for insomnia, psychopathology, and indices of disrupted neuroplasticity. On the other hand, pharmacological pathways for insomnia treatment in these mental conditions are still not well defined. Therapeutic options acting on melatonergic systems and new therapeutic options acting on orexinergic systems may represents interesting pathways of interventions that may open new windows on insomnia treatment in mental disorders.

Sleep, insomnia and mental health

For hundreds of years, mankind has been influencing its sleep and waking state through the adenosinergic system. For ~100 years now, systematic research has been performed, first started by testing the effects of different dosages of caffeine on sleep and waking behaviour. About 70 years ago, adenosine itself entered the picture as a possible ligand of the receptors where caffeine hooks on as an antagonist to reduce sleepiness. Since the scientific demonstration that this is indeed the case, progress has been fast. Today, adenosine is widely accepted as an endogenous sleep‐regulatory substance. In this review, we discuss the current state of the science in model organisms and humans on the working mechanisms of adenosine and caffeine on sleep. We critically investigate the evidence for a direct involvement in sleep homeostatic mechanisms and whether the effects of caffeine on sleep differ between acute intake and chronic consumption. In addition, we review the more recent evidence that adenosine levels may also influence the functioning of the circadian clock and address the question of whether sleep homeostasis and the circadian clock may interact through adenosinergic signalling. In the final section, we discuss the perspectives of possible clinical applications of the accumulated knowledge over the last century that may improve sleep‐related disorders. We conclude our review by highlighting some open questions that need to be answered, to better understand how adenosine and caffeine exactly regulate and influence sleep.

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Adenosine, caffeine, and sleep–wake regulation: state of the science and perspectives

Disrupted sleep is a major feature in numerous clinical disorders and is related to decrements in affective memory processing. The prevalence of sleep disruption in post-traumatic stress disorder (PTSD) is suggested to be a key feature that exacerbates the impaired ability to recall extinction memories during experimental fear conditioning. We hypothesized that an intervention employing blue-wavelength light therapy (BLT) to regulate sleep and stabilize circadian rhythms in patients with PTSD (i.e., via regulated morning exposure) would be associated with PTSD symptom improvement, decreased sleep-related complaints, as well as improved consolidation and retention of extinction memories relative to a fear conditioning/extinction paradigm. Eighty-two individuals with PTSD underwent a well-validated fear conditioning/extinction protocol with subsequent assignment to receive morning BLUE (BLT) or placebo AMBER (ALT) light therapy daily for 30-min over 6-weeks. Participants returned after the intervention for post-treatment extinction recall, comprised of exposure to the previously conditioned stimuli, with the difference in skin conductance response between the “extinguished” and the “never-extinguished” stimuli at follow-up. Participants also viewed previously conditioned stimuli in a novel context during a functional magnetic resonance imaging (fMRI) scan. BLUE light therapy was associated with improvements relative to correlated decreases between PTSD symptoms and sleep-related complaints. Participants receiving BLT also sustained retention of the extinction memory, while those in the placebo amber light treatment group showed impairment, characterized by the restoration of the extinguished fear response after 6-weeks. Participants in the ALT also demonstrated greater reactivity in the left insula when viewing the previously extinguished fear-conditioned stimuli in a novel context. Daily BLUE-wavelength morning light exposure was associated with greater retention of extinction learning in patients with PTSD when compared to ALT, as supported by both autonomic and neurobiological reactivity. We speculate that improved sleep facilitated by a stabilized circadian rhythm, after fear-learning, led to greater consolidation of the fear extinction memory, decreased PTSD symptom presentation, and associated decreases in sleep-related complaints. Prominent exposure treatments for PTSD incorporate principles of fear extinction, and our findings suggest that blue light treatment may facilitate treatment gains by promoting the consolidation of extinction memories via improved sleep.

/pdf/morning-blue-light-treatment-improves-sleep-complaints-2h0occoq.pdf

Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder

The influence of sleep on fear extinction in trauma-related disorders

http://www.thelancet.com/article/S2213260023001248/pdf

Effects of sleep disturbance on dyspnoea and impaired lung function following hospital admission due to COVID-19 in the UK: a prospective multicentre cohort study

Massimo Fornasier

Papers

Sleep and anxiety: From mechanisms to interventions