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.

Dimensionality of the Pittsburgh Sleep Quality Index: a systematic review.

BACKGROUND: The Pittsburgh Sleep Quality Index (PSQI) dimensionality is much debated, with the greatest number of reported factor structures. Therefore, this review appraised the methodologies of studies investigating the factor structure of the PSQI. MATERIAL AND METHODS: MEDLINE, PsycInfo, AJOL, BASE, Cochrane Library, Directory of Open Access Journals (Lund University), CINAHL, and Embase were searched systematically to include articles published till 23rd March, 2018. The articles with the objective of factor analysis of the PSQI (20 articles) or with a major section on the same subject (25 articles) were included. There was no limitation about participant characteristics. Descriptive analysis of articles for measures of the suitability of the data for factor analysis, details of the exploratory factor analysis (EFA) and details of the confirmatory factor analysis (CFA) was performed. RESULTS: The analysis used by the majority did not employ the simplest scheme for interpreting the observed data: the parsimony principle. Other shortcomings included under- or non-reporting of sample adequacy measures (11 out of 45 articles), non-use of EFA (20 out of 45 articles), use of EFA without relevant details, non-use of CFA (11 out of 45 articles), and use of CFA without relevant details. Overall, 31 out of 45 articles did not use either EFA or CFA. CONCLUSION: We conclude that the various PSQI factor structures for standard sleep assessment in research and clinical settings may need further validation. TRIAL REGISTRATION: Not applicable because this was a review of existing literature.

Sleep disturbances and memory impairment among pregnant women consuming khat: An under-recognized problem.

Khat (Catha edulis) is a evergreen flowering shrub that is cultivated at high altitudes, especially in East Africa and the southwest of the Arabian Peninsula. The plant contains alkaloids, of which cathinone and cathine have structural similarity and pharmacological action similar to amphetamines. The leaves are, therefore, consumed in some regions as a psychoactive stimulant due to cultural beliefs and misperceptions on the health benefits of khat consumption. This resulted in a growing prevalence of khat consumption among pregnant women. The myriad of physiological changes associated with pregnancy impairs sleep and memory. Moreover, khat has also been shown to have adverse effects on memory and sleep. Therefore, its use during pregnancy may further aggravate those impairments. The purpose of this mini-review is to summarize the changes in sleep and memory during pregnancy and the evidence supporting a relationship between khat consumption and neurocognitive deficits and sleep dysfunctions. The misperceptions of beneficial effects of khat, the high prevalence of consumption among pregnant women, and the possibility of under-reporting of khat abuse do necessitate the development of alternative methodologies to identify cases of unreported khat abuse in pregnant women. It is proposed that screening for sleep problems and memory deficits may help identify under-reported cases of khat abuse in pregnant women.

Racial/Ethnic and Social Inequities in Sleep Medicine: The Tip of the Iceberg?

PURPOSE: It is known that racial disparities exist in terms of disease prevalence and access to health care. However, the link between race/ethnicity and sleep quality is often under-recognized. RESULTS: Current evidence shows that differences exist between Blacks and Whites in terms of sleep duration, sleep quality, and the likelihood of acquiring a sleep disorder. It has been argued that the adverse effects of ethnicity on sleep quality or duration interact with other social or personal factors (such as employment) and that the effects of these factors are interactive and need to be analyzed simultaneously. There is a growing body of evidence showing that disturbed sleep is a mediator of the effect of environmental stressors on personal health, which is more pronounced in ethnic minorities. CONCLUSIONS: These findings support the notion that perceived discrimination or unfair treatment has significant associations with complaints of sleep disturbance and disturbed objective measures of sleep quality and sleep architecture. Hence, greater efforts are needed to demonstrate how racial/ethnic factors influence different sleep processes.

Electrolyte imbalance and sleep problems during anti-retroviral therapy: an under-recognized problem.

Human immunodeficiency virus (HIV) infection, and the anti-retroviral therapy (ART) associated complications necessitate that the medical care system keeps evolving for proper management of this group of patients. Electrolyte imbalance and sleep problems are common in patients on ART. Both of these conditions are associated with increased morbidity (such as acute kidney injury, chronic kidney disease, low CD4 count, non-adherence and depression) and mortality. Therefore, screening for both sleep problems and electrolytes imbalance may help to decrease the risk of complications in patients on ART.

Comorbid depression in obstructive sleep apnea: an under-recognized association.

BACKGROUND: Obstructive sleep apnea (OSA) and depression may coexist in the same patient. This article aims to review the link between OSA and comorbid depression and critically evaluate the results of studies that assessed the correlation between OSA and depression, the impact of OSA treatment on comorbid depression, and the impact of comorbid depression on continuous positive airway pressure (CPAP) adherence. METHODS: An integrative review was conducted on English language studies and reports that assessed the relationship between OSA and depression. Studies were identified by searching PubMed, Web of Science and Google Scholar databases, and reference lists of included studies. RESULTS: Generally, cross-sectional studies show a higher prevalence of depression among OSA patients with both community and sleep disorder clinic samples. Nevertheless, the relationship between OSA and depression is complicated by the fact that the disorders have overlapping symptoms. Longitudinal studies demonstrate an increased risk of developing depression among people with OSA, as well as an association between OSA severity and the likelihood of developing depression. On the other hand, studies assessing the impact of CPAP therapy on depression among OSA patients report conflicting results. Therefore, it is essential to consider how the disorders affect one another and to understand the clinical consequences of treating each disorder in isolation. CONCLUSION: Depression is prevalent among patients with OSA both in the community and in sleep disorder clinics. Clinicians in general should be aware of this significant association and should aim to treat both disorders.

Measurement of melatonin in body fluids: standards, protocols and procedures.

BACKGROUND AND PURPOSE: The circadian rhythm of melatonin in saliva or plasma, or of the melatonin metabolite 6-sulfatoxymelatonin (a6MTs) in urine, is a defining feature of suprachiasmatic nucleus (SCN) function, the body's endogenous oscillatory pacemaker. The primary objective of this review is to ascertain the clinical benefits and limitations of current methodologies employed for detection and quantification of melatonin in biological fluids and tissues. DATA IDENTIFICATION: A search of the English-language literature (Medline) and a systematic review of published articles were carried out. STUDY SELECTION: Articles that specified both the methodology for quantifying melatonin and indicated the clinical purpose were chosen for inclusion in the review. DATA EXTRACTION: The authors critically evaluated the methodological issues associated with various tools and techniques (e.g. standards, protocols, and procedures). RESULTS OF DATA SYNTHESIS: Melatonin measurements are useful for evaluating problems related to the onset or offset of sleep and for assessing phase delays or advances of rhythms in entrained individuals. They have also become an important tool for psychiatric diagnosis, their use being recommended for phase typing in patients suffering from sleep and mood disorders. Additionally, there has been a continuous interest in the use of melatonin as a marker for neoplasms of the pineal region. Melatonin decreases such as found with aging are or post pinealectomy can cause alterations in the sleep/wake cycle. The development of sensitive and selective methods for the precise detection of melatonin in tissues and fluids has increasingly been shown to have direct relevance for clinical decision making. CONCLUSIONS: Due to melatonin's low concentration, as well as the coexistence of numerous other compounds in the blood, the routine determination of melatonin has been an analytical challenge. The available evidence indicates however that these challenges can be overcome and consequently that evaluation of melatonin's presence and activity can be an accessible and useful tool for clinical diagnosis.

Malaria: therapeutic implications of melatonin.

Malaria, which infects more than 300 million people annually, is a serious disease. Epidemiological surveys indicate that of those who are affected, malaria will claim the lives of more than one million individuals, mostly children. There is evidence that the synchronous maturation of Plasmodium falciparum, the parasite that causes a severe form of malaria in humans and Plasmodium chabaudi, responsible for rodent malaria, could be linked to circadian changes in melatonin concentration. In vitro melatonin stimulates the growth and development of P. falciparum through the activation of specific melatonin receptors coupled to phospholipase-C activation and the concomitant increase of intracellular Ca2+. The Ca2+ signaling pathway is important to stimulate parasite transition from the trophozoite to the schizont stage, the final stage of intraerythrocytic cycle, thus promoting the rise of parasitemia. Either pinealectomy or the administration of the melatonin receptor blocking agent luzindole desynchronizes the parasitic cell cycle. Therefore, the use of melatonin antagonists could be a novel therapeutic approach for controlling the disease. On the other hand, the complexity of melatonin's action in malaria is underscored by the demonstration that treatment with high doses of melatonin is actually beneficial for inhibiting apoptosis and liver damage resulting from the oxidative stress in malaria. The possibility that the coordinated administration of melatonin antagonists (to impair the melatonin signal that synchronizes P. falciparum) and of melatonin in doses high enough to decrease oxidative damage could be a novel approach in malaria treatment is discussed.

Potential use of melatonergic drugs in analgesia: mechanisms of action.

Melatonin is a remarkable molecule with diverse physiological functions. Some of its effects are mediated by receptors while other, like cytoprotection, seem to depend on direct and indirect scavenging of free radicals not involving receptors. Among melatonin's many effects, its antinociceptive actions have attracted attention. When given orally, intraperitoneally, locally, intrathecally or through intracerebroventricular routes, melatonin exerts antinociceptive and antiallodynic actions in a variety of animal models. These effects have been demonstrated in animal models of acute pain like the tail-flick test, formalin test or endotoxin-induced hyperalgesia as well as in models of neuropathic pain like nerve ligation. Glutamate, gamma-aminobutyric acid, and particularly, opioid neurotransmission have been demonstrated to be involved in melatonin's analgesia. Results using melatonin receptor antagonists support the participation of melatonin receptors in melatonin's analgesia. However, discrepancies between the affinity of the receptors and the very high doses of melatonin needed to cause effects in vivo raise doubts about the uniqueness of that physiopathological interpretation. Indeed, melatonin could play a role in pain through several alternative mechanisms including free radicals scavenging or nitric oxide synthase inhibition. The use of melatonin analogs like the MT(1)/MT(2) agonist ramelteon, which lacks free radical scavenging activity, could be useful to unravel the mechanism of action of melatonin in analgesia. Melatonin has a promising role as an analgesic drug that could be used for alleviating pain associated with cancer, headache or surgical procedures.

Ramelteon: a review of its therapeutic potential in sleep disorders.

Ramelteon is a tricyclic synthetic analog of melatonin that acts specifically on MT(1) and MT(2) melatonin receptors. Ramelteon's half-life is longer than that of melatonin, being metabolized in the body to four main metabolites, M-I, M-II, M-III, and M-IV. M-II has an affinity to MT(1) and MT(2) of about one-tenth of the parent compound, but its concentration in the circulation exceeds that of ramelteon by more than an order of magnitude. Ramelteon is effective in decreasing latency to persistent sleep and increasing total sleep time in freely moving monkeys. A number of clinical studies have been undertaken to study the efficacy of ramelteon in subjects with chronic insomnia. In almost all of these studies, ramelteon, in various doses of 4, 8, or 16 mg most commonly, significantly reduced sleep latency and increased sleep duration. Its primary action in sleep promotion is not a generalized gamma-aminobutyric (GABA)-ergic central nervous system depression, but rather it acts as a melatonergic agonist in the suprachiasmatic nucleus (and at other central nervous system sites), from where downstream processes, including GABA-ergic effects, are controlled via the hypothalamic sleep switch. Unlike other commonly prescribed hypnotic drugs, ramelteon is not associated with next morning hangover effects or reductions in alertness, nor has it been shown to cause withdrawal symptoms. The adverse symptoms reported with ramelteon are mild. All long-term investigations that have been carried out support the conclusion that ramelteon is a well tolerated and effective drug for the treatment of insomnia.

Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine.

Depression is a family of complex and multifactorial illnesses that are characterized by disruptions in the functioning of a number of physiological, neuroendocrine and behavioral processes. Of these, sleep disturbance and circadian rhythm abnormalities constitute the most prevalent signs of depressive illness. Difficulty in falling asleep, decreases in total sleep time and sleep efficiency, early morning awakenings, and rapid eye movement sleep alterations are all commonly seen in depressed patients. Advances or delays in the phase of circadian rhythms have been documented in patients with major depressive disorder (MDD), bipolar disorder and patients with seasonal affective disorder (SAD). The disturbances in the amplitude and rhythm of melatonin secretion that occur in patients with depression resemble those seen in subjects with chronobiological disorders. The finding that insomnia and circadian rhythm abnormalities are prominent features in depression suggests that a close link exists between melatonin secretion disturbance and depressed mood. This inference has been further strengthened by the finding that agomelatine, a recently introduced melatonergic agent with a novel mechanism of action, has beneficial effects in patients with MDD, bipolar disorder or SAD. Among agomelatine's characteristics are a rapid onset of action and a pronounced effectiveness for improving sleep efficiency and correcting circadian rhythm abnormalities. Disruptions in melatonin secretion or availability may be the common factor, which underlies depressive disorder and its prominent signs and symptoms such as sleep and circadian rhythm abnormalities.

Efficacy and tolerability of indiplon in older adults with primary insomnia.

OBJECTIVE: To evaluate the efficacy and safety of indiplon in elderly patients with primary insomnia. PATIENTS AND METHODS: Elderly patients, 65-80 years (N=358; 55% female; mean age, 71 years) who met the criteria for primary insomnia according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) for three months were randomized to two weeks of double-blind nightly treatment with 5 mg or 10 mg indiplon or placebo. Daily self-assessments by the patients included latency to sleep onset (LSO), total sleep time (TST), number of awakenings (NAW), wake time after sleep onset (WASO), and sleep quality. Data were collected between July, 2002, and October, 2003, at 52 clinical research sites in North America. RESULTS: Treatment with indiplon was associated with significant reduction in LSO at Week 1 for the 5 mg (34.6+/-1.8 min) and 10 mg doses (30.4+/-1.6 min) relative to placebo (47.4+/-2.5 min; p<0.0001 for both comparisons). During Week 2, LSO remained shorter on both indiplon doses compared to placebo (5 mg, p=0.016; and 10 mg, p=0.0028). During both study weeks, treatment with indiplon was also associated with significant improvement, relative to placebo, in TST, NAW, WASO, and sleep quality. The frequency of adverse events was similar in the indiplon 5 mg and placebo groups; somnolence, nausea, depression and decreased appetite were slightly more common in the indiplon 10 mg group. CONCLUSION: In elderly patients with primary insomnia, indiplon 5 mg and 10 mg were efficacious in inducing and maintaining sleep and improving sleep quality during the two weeks of treatment. Indiplon 5mg was well-tolerated, with no serious adverse events and no significant changes in electrocardiogram (ECG) or routine clinical laboratory evaluations; the 10mg dose produced slightly greater efficacy as well as somewhat increased adverse events.

A placebo-controlled study of sertraline in the treatment of outpatients with seasonal affective disorder.

RATIONALE: Seasonal affective disorder (SAD) is a relatively common cyclical depressive illness characterized by seasonal depressions during winter. The disorder is commonly responsive to light therapy, but antidepressant drug efficacy has not been definitely established. Serotonin selective re-uptake inhibitors are potentially efficacious treatments for SAD. OBJECTIVES: The objective of this study was to evaluate the efficacy, tolerability and safety of sertraline treatment for SAD. METHODS: One hundred and eighty seven outpatients with seasonal pattern recurrent winter depression (DSM-III-R defined) and a minimum 29-item Hamilton depression scale (SIGH-SAD version) score of 22 were randomized to 8 weeks treatment with either sertraline or placebo in a double-blind, multi-country, multi-center, parallel-group, flexible dose (50-200 mg once daily) study. Efficacy was investigated using physician and patient-rated scales measuring depression, anxiety and symptoms characteristic of seasonal affective disorder. RESULTS: Sertraline produced a significantly greater response than placebo at endpoint as measured by changes in the 29-item and 21-item Hamilton depression scales, the clinical global impression (CGI) severity scale, the Hamilton anxiety scale, and the hospital anxiety and depression scale. The proportion of sertraline-treated subjects achieving a response on the CGI improvement rating (ratings of 1 or 2) at endpoint (last observation carried forward) was significantly greater than that of the placebo group. Overall sertraline was well tolerated with the most frequent placebo adjusted adverse events, being nausea, diarrhea, insomnia and dry mouth. Adverse events were mostly mild to moderate and transient. CONCLUSIONS: Sertraline pharmacotherapy has been demonstrated to be an effective and well-tolerated therapy for out patients with SAD. As such, sertraline offers an important pharmacological option in the clinical management of this condition.

Development of an adjective checklist to measure five FACES of fatigue and sleepiness. Data from a national survey of insomniacs.

Development and initial validation of the FACES of fatigue and sleepiness adjective checklist. An initial item pool of 65 adjectives, descriptive of fatigue, sleepiness and related deprivation states, was developed and administered to 372 individuals referred by their family physicians for psychiatric investigation and treatment of severe insomnia. Participants attended one of six Canadian university-affiliated sleep clinics where they completed a psychiatric assessment and a 766-item questionnaire, including a number of standard indices of sleep-related behavior and symptoms, medical history, sleep hygiene, psychosocial well-being and psychopathology. Principal-components and item analyses were undertaken to refine the initial 65-item pool to a smaller 50-item set, consisting of five subscales: Fatigue, Anergy, Consciousness, Energized and Sleepiness. Coefficient alpha was calculated and indicated high internal consistency reliability for all subscales. Convergent and discriminant validity were also evaluated by calculating correlations between FACES subscales and a number of independent indices. The resulting five-scale FACES questionnaire appears to offer a promising self-report instrument for the measurement of fatigue and related subjective experiences.

Atypical sexual behavior during sleep.

OBJECTIVE: This article reports a case series of atypical sexual behavior during sleep, which is often harmful to patients or bed partners. METHODS: Eleven subjects underwent clinical evaluation of complaints of sleep-related atypical sexual behavior. Complaints included violent masturbation, sexual assaults, and continuous (and loud) sexual vocalizations during sleep. One case was a medical-legal case. Sleep logs, clinical evaluations, sleep questionnaires, structured psychiatric interviews, polysomnography, actigraphy, home electroencephalographic monitoring during sleep, and clinical electroencephalographic monitoring while awake and asleep were used to determine clinical diagnoses. RESULTS: Atypical sexual behaviors during sleep were associated with feelings of guilt, shame, and depression. Because of these feelings, patients and bed partners often tolerated the abnormal behavior for long periods of time without seeking medical attention. The following pathologic sleep disorders were demonstrated on polysomnography: partial complex seizures, sleep-disordered breathing, stage 3 to 4 non-rapid eye movement (REM) sleep parasomnias, and REM sleep behavior disorder. These findings were concurrent with morning amnesia. CONCLUSIONS: The atypical behaviors were related to different syndromes despite the similarity of complaints from bed partners. In most cases the disturbing and often harmful symptoms were controlled when counseling was instituted and sleep disorders were treated. In some cases treatment of seizures or psychiatric disorders was also needed. Clonazepam with simultaneous psychotherapy was the most common successful treatment combination. The addition of antidepressant or antiepileptic medications was required in specific cases.