Timing is everything: Circadian rhythms and their role in the control of sleep.

Sleep and the circadian clock are intertwined and have persisted throughout history. The suprachiasmatic nucleus (SCN) orchestrates sleep by controlling circadian (Process C) and homeostatic (Process S) activities. As a "hand" on the endogenous circadian clock, melatonin is critical for sleep regulation. Light serves as a cue for sleep/wake control by activating retino-recipient cells in the SCN and subsequently suppressing melatonin. Clock genes are the molecular timekeepers that keep the 24 h cycle in place. Two main sleep and behavioural disorder diagnostic manuals have now officially recognised the importance of these processes for human health and well-being. The body's ability to respond to daily demands with the least amount of effort is maximised by carefully timing and integrating all components of sleep and waking. In the brain, the organization of timing is essential for optimal brain physiology.

Chronobiological theories of mood disorder.

Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately 100 million adults worldwide. The disorder is characterized by a constellation of symptoms affecting mood, anxiety, neurochemical balance, sleep patterns, and circadian and/or seasonal rhythm entrainment. However, the mechanisms underlying the association between chronobiological parameters and depression remain unknown. A PubMed search was conducted to review articles from 1979 to the present, using the following search terms: "chronobiology," "mood," "sleep," and "circadian rhythms." We aimed to synthesize the literature investigating chronobiological theories of mood disorders. Current treatments primarily include tricyclic antidepressants and selective serotonin reuptake inhibitors, which are known to increase extracellular concentrations of monoamine neurotransmitters. However, these antidepressants do not treat the sleep disturbances or circadian and/or seasonal rhythm dysfunctions associated with depressive disorders. Several theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chronobiological approach, including timely use of light and melatonin agonists, could complement the treatment of MDD.

Neuropsychiatric Consequences of COVID-19 Pandemic: A Synthetic Review from a Global Perspective.

Some research suggests that distress, secondary to isolation and fear following COVID-19 infection, can negatively affect the long-term more than the COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors, ranging from the direct effect of infection, to the body's responses against the infection, or to the psychological sequelae of social isolation, unemployment, and fear for one's health and livelihood. Current findings show that the more severe the respiratory infection, the more likely are central nervous system (CNS) complications regarding the infection itself. The immune reactions to the infection may result in symptoms similar to chronic fatigue as well as neurocognitive deficits, which last long after the infection is gone. An increase in symptoms of depression, anxiety, and trauma-related stress may also follow upon economic fears and isolation from friends and family. The consequences of the pandemic are not limited to adults; children learning remotely and away from classmates and routine activities may develop adjustment disorders, acute stress disorder, and a variety of manifestations of grief. A summary of case reports suggests that COVID-19-related stress, economic recession, and political unrest increase the risk of suicidal behaviors and acts of violence. However, it is unknown whether manifestations of mental disorders result from social causes or whether CNS complications may be responsible.

'Distant socializing,' not 'social distancing' as a public health strategy for COVID-19.

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing. However, socializing in a safe context (i.e. over the phone, video-chat, etc.) is especially important during this time of crisis. Therefore, in this narrative review, we suggest the term 'distant socializing' as more apt expression, to promote physical distancing measures while also highlighting the importance of maintaining social bonds. Further, articles discussing the practice, implementation, measurement, and mental health effects of physical distancing are reviewed. Physical distancing is associated with psychiatric symptoms (such as anxiety and depression), suicidal ideation, and domestic violence. Further, unemployment and job insecurity have significantly increased during COVID-19, which may exacerbate these negative mental health effects. Governments, medical institutions, and public health bodies should therefore consider increasing mental health resources both during and after the pandemic, with a specific focus on frontline workers, COVID-19 survivors, and marginalized communities.

Basic chronobiology: what do sleep physicians need to know?

Sleep is an essential physiological process, which profoundly affects a wide range of biological activities. It is now known that sleep supports myriad vital functions in the central nervous system. This includes neural plasticity, learning, memory, cognition and emotional regulation. Additionally, it affects basic processes such as cardiovascular, immunological and metabolic activity. Evidence from multiple lines of research has thus shown that good quality of sleep is essential for both survival and optimal functioning of life. Considerable evidence also supports the conclusion that even minimal dysfunctions in circadian regulation can significantly disrupt sleep and broadly affect body physiology. As a consequence, it is now appreciated that the therapy of sleep disorders is more complex than was once thought. At present, several clinical disciplines have recognized the significance of the biological clock in health and illness, and are incorporating this knowledge into treatment programs. Recent decades have seen the emergence of chronotherapies, i.e., treatment strategies that are aimed at producing adjustments in the circadian clock. The final objective of these approaches is to affect basic cellular and physiological processes, which in turn may be at the root of disorders such as physiological aging, immune functioning, metabolic activity, and psychiatric disturbance. It is suggested that the integration of chronobiological perspectives into many mainstream medical disciplines would be of significant benefit, both for the reduction of the prevalence of diseases and their treatment. This review considers the physiology of sleep and the importance of timekeeping mechanisms in the regulation of overall health.

Chronotherapeutics: Recognizing the Importance of Timing Factors in the Treatment of Disease and Sleep Disorders.

This review describes the characteristics of a number of pathologies, which are considered from the point of view of chronobiology, that is, the way in which biological processes are expressed throughout the 24-hour day. This perspective is a relatively new way of thinking about disease and additionally about how to treat diseases. It has called attention to the importance of not only the quantity of a drug that is administered but also when it is administered. In addition, the review presents an overview of the emerging clinical strategies known as chronotherapeutics, that is, the effects of the daily scheduling of drug administration and the consequences of the activity and efficacy of therapies that are applied in this manner. This article also reviews innovative ways in which physicians are applying time-specified drug treatment (chronopharmacology) for sleep disorders. Here, we present a systematic description of chronopharmacology as well as definitions of key terms that, we believe, will be helpful for newcomers to the field. It is hoped that greater awareness of this new perspective on pharmacology will promote its adoption by researchers and clinicians.

The association of BDNF gene polymorphism with cognitive impairment in insomnia patients.

BACKGROUND: Reductions in BDNF activity have shown associations with depressed mood. Other evidence has demonstrated that the BDNF Val66Met polymorphism (rs6265) appears to reduce neural plasticity. A limited number of studies have investigated the influence of these genetic polymorphisms in insomnia. The present study sought to confirm the presence of associations between BDNF Val66Met polymorphism (rs6265) occurrence in normal sleepers and those with insomnia. METHOD: The study subjects consisted of a patient group (n = 199) complaining of insomnia and a control group (n = 51). Each subject was clinically interviewed using questions taken from the Brief Insomnia Questionnaire. After the interview, the subjects were asked to complete the Insomnia Severity Index, The Hamilton Depression Rating Scale, and the Montreal Cognitive Assessment Test. An overnight polysomnography test was also administered. Blood samples were collected for genetic study. RESULTS: The insomnia patients showed a greater prevalence of heterozygous (A/G) VAL/MET polymorphism than the normal controls (p = ≤ 0.0001). This finding confirmed that this genetic polymorphism, which impairs BDNF activity, is an important correlate of disturbed sleep. Further, the finding of significantly greater (p = ≤ 0.0001) depression scores among the insomnia group suggested that BDNF is an important factor in the development of depressive symptoms. CLINICAL IMPLICATIONS: The results of the present study indicate that BDNF gene polymorphism plays a prominent role in the variation of symptoms among insomnia patients and, further, that this polymorphism is strongly related to the severity of depression.

Obstructive sleep apnea: personal, societal, public health, and legal implications.

Introduction Obstructive sleep apnea (OSA) is a widely prevalent sleep-related breathing disorder, which leads to several life-threatening diseases. OSA has systemic effects on various organ systems. Untreated OSA is associated with long-term health consequences including hypertension, heart disease, diabetes, depression, metabolic disorders, and stroke. In addition, untreated OSA is reported to be associated with cognitive dysfunction, impaired productivity at the workplace and in an increased risk of motor vehicle accidents (MVAs) resulting in injury and fatality. Other consequences of OSA include, but are not limited to, impaired vigilance, daytime somnolence, performance deficits, morning headaches, mood disturbances, neurobehavioral impairments, and general malaise. Additionally, OSA has become an economic burden on most health systems all over the world. Many driving license regulations have been developed to reduce MVAs among OSA patients. Methods Studies of the personal, societal, public health, and legal aspects of OSA are reviewed. Data were collected through the following databases: MEDLINE, Google Scholar, Scopus, SAGE Research Methods, and ScienceDirect. Conclusion OSA leads to worsening of patients' personal relationships, decreasing work productivity, and increasing occupational accidents as well as MVAs. The costs of undiagnosed and untreated OSA to healthcare organizations are excessive. Thus, proper management of OSA will benefit not only the patient but will also provide widespread benefits to the society as a whole.