Summary Chronic insomnia is defined by difficulties in falling asleep, maintaining sleep, and early morning awakening, and is coupled with daytime consequences such as fatigue, attention deficits, ...and mood instability. These symptoms persist over a period of at least 3 months (Diagnostic and Statistical Manual 5 criteria). Chronic insomnia can be a symptom of many medical, neurological, and mental disorders. As a disorder, it incurs substantial health-care and occupational costs, and poses substantial risks for the development of cardiovascular and mental disorders, including cognitive deficits. Family and twin studies confirm that chronic insomnia can have a genetic component (heritability coefficients between 42% and 57%), whereas the investigation of autonomous and central nervous system parameters has identified hyperarousal as a final common pathway of the pathophysiology, implicating an imbalance of sleep–wake regulation consisting of either overactivity of the arousal systems, hypoactivity of the sleep-inducing systems, or both. Insomnia treatments include benzodiazepines, benzodiazepine-receptor agonists, and cognitive behavioural therapy. Treatments currently under investigation include transcranial magnetic or electrical brain stimulation, and novel methods to deliver psychological interventions.
Depressive syndromes are frequent and heterogeneous brain conditions with more than 90% of patients suffering from sleep complaints. Better characterizing this “sleep” domain may allow to both better ...treat acute episodes with existing chronotherapeutics, but also to prevent the manifestation or recurrences of mood disorders. This work aims to i) review theoretical and fundamental data of chronotherapeutics, and ii) provide practical recommendations. Light therapy (LT) can be used as a first-line monotherapy of moderate to severe depression of all subtypes. LT can be also used as a combination with antidepressant to maximize patients’ response rates, which has a clear superiority to antidepressant alone. Sleep deprivation (SD) is a rapid and powerful chronotherapeutic with antidepressant responses within hours in 45-60% of patients with unipolar or bipolar depression. Different strategies should be combined to stabilize the SD antidepressant effect, including concomitant medications, repeated SD, combination with sleep phase advance and/or LT (triple chronotherapy). Melatonin treatment is of interest in remitted patients with mood disorder to prevent relapses or recurrences, if a complaint of insomnia, poor sleep quality or phase delay syndrome is associated. During the acute phase, melatonin could be used as an adjuvant treatment for symptoms of insomnia associated with depression. The cognitive behavioral therapy for insomnia (CBT-I) can be recommend to treat insomnia during euthymic phases. The Interpersonal and social rhythm therapy (IPSRT) is indicated for the acute treatment of bipolar depression and for the prevention of mood episodes. Chronotherapeutics should always be associated with behavioral measures for healthy sleep.
•Light therapy is recommended as a first-line monotherapy for all depression subtypes.•Sleep deprivation has a rapid action stabilized with triple chronotherapy.•Melatonin use in case of insomnia, poor sleep quality or phase delay syndrome.•IPSRT and CBTI-BP as preventive strategies for both depressive and manic episodes.•IPSRT is also recommended in acute depressive bipolar depression.
Previous research has identified insomnia as a predictor for the onset of depression. The aim of this meta-analysis is to investigate whether insomnia also predicts the onset of other mental ...disorders. Longitudinal studies were eligible for inclusion if they investigated insomnia at baseline (including nighttime- and daytime-symptoms) as a predictor of the later onset of psychopathology within a follow-up time-frame of at least 12 mo. Thirteen primary studies were included. The results suggest that insomnia is a significant predictor for the onset of depression (10 studies, OR 2.83, CI 1.55–5.17), anxiety (six studies, OR 3.23, CI 1.52–6.85), alcohol abuse (two studies, OR 1.35, CI 1.08–1.67, and psychosis (one study, OR 1.28, CI 1.03–1.59). The overall risk of bias in the primary studies was moderate. This meta-analysis provides evidence that insomnia increases the risk for psychopathology. A future research agenda should include more prospective studies using established diagnostic criteria, assessing insomnia at baseline and including long-term follow-up intervals evaluating a wider range of mental disorders. In addition, prospective long-term interventional studies investigating the efficacy of insomnia treatment for the prevention of mental disorders are called for.
Introduction
Insomnia is a stress-related sleep disorder, may favor a state of allostatic overload impairing brain neuroplasticity, stress immune and endocrine pathways, and may contribute to mental ...and physical disorders. In this framework, assessing and targeting insomnia is of importance.
Aim
Since maladaptive neuroplasticity and allostatic overload are hypothesized to be related to GABAergic alterations, compounds targeting GABA may play a key role. Accordingly, the aim of this review was to discuss the effect of GABA
A
receptor agonists, short-medium acting hypnotic benzodiazepines and the so called Z-drugs, at a molecular level.
Method
Literature searches were done according to PRISMA guidelines. Several combinations of terms were used such as “hypnotic benzodiazepines” or “brotizolam,” or “lormetazepam” or “temazepam” or “triazolam” or “zolpidem” or “zopiclone” or “zaleplon” or “eszopiclone” and “insomnia” and “effects on sleep” and “effect on brain plasticity” and “effect on stress system”. Given the complexity and heterogeneity of existing literature, we ended up with a narrative review.
Results
Among short-medium acting compounds, triazolam has been the most studied and may regulate the stress system at central and peripheral levels. Among Z-drugs eszopiclone may regulate the stress system. Some compounds may produce more “physiological” sleep such as brotizolam, triazolam, and eszopiclone and probably may not impair sleep processes and related neural plasticity. In particular, triazolam, eszopiclone, and zaleplon studied
in vivo
in animal models did not alter neuroplasticity.
Conclusion
Current models of insomnia may lead us to revise the way in which we use hypnotic compounds in clinical practice. Specifically, compounds should target sleep processes, the stress system, and sustain neural plasticity. In this framework, among the short/medium acting hypnotic benzodiazepines, triazolam has been the most studied compound while among the Z-drugs eszopiclone has demonstrated interesting effects. Both offer potential new insight for treating insomnia.
Highlights • Sleep loss is common during pregnancy. It may account for its adverse outcomes. • Common pathophysiological mechanisms are related to stress system activation. • Sleep loss may lead to ...stress “overload” contributing to adverse pregnancy outcomes. • Sleep loss during pregnancy can be regarded as a stress results and as a stressor per se.
Coronavirus disease 2019 (COVID-19) seriously affected the whole of Italy. The extreme virulence and the speed of propagation resulted in restrictions and home confinement. This change was ...immediately perceived by people who found themselves exposed to feelings of uncertainty, fear, anger, stress, and a drastic change in the diurnal but above all nocturnal lifestyle. For these reasons, we aimed to study the quality of sleep and its connection to distress levels and to evaluate how lifestyle changed in the Italian population during the lockdown.
By means of an Internet survey we recruited 6,519 adults during the whole of the COVID-19 lockdown (from March 10-1st phase to May 4-2nd phase). We investigated the sociodemographic and COVID-19-related information and assessed sleep quality using the Medical Outcomes Study-sleep scale (MOS-SS) and mental health with the short form of Depression, Anxiety, and Stress Scales-21 Items (DASS-21). Multiple logistic regression model was used to evaluate the multivariate association between the dependent variable (good sleeper vs. poor sleeper) and all the variables that were significant in the univariate analysis.
A total of 3,562 (55.32%) participants reported poor sleep quality according to the MOS-Sleep Index II score. The multiple binary logistic regression results of poor sleepers revealed several risk factors during the outbreak restrictions: female gender, living in Central Italy, having someone close who died because of COVID-19, markedly changed sleep-wake rhythms characterized by earlier or postponed habitual bedtime, earlier habitual awakening time and reduced number of afternoon naps, and extremely severe levels of stress, anxiety, and depression.
This is the first study designed to understand sleep quality and sleep habits during the whole of the lockdown period in the Italian population that provides more than 6,000 participants in a survey developed specifically for the health emergency related to COVID-19. Our study found that more than half of the Italian population had impaired sleep quality and sleep habits due to elevated psychological distress during the COVID-19 lockdown containment measures. A multidisciplinary action should be undertaken in order to plan appropriate responses to the current crisis caused by the lockdown for the COVID-19 outbreak.
A compelling number of studies, conducted in both children and adults, have reported an association between sleep disturbances/circadian sleep alterations and autism spectrum disorder (ASD); however, ...the data are sparse and the nature of this link is still unclear. The present review aimed to systematically collect the literature data relevant on sleep disturbances and circadian sleep dysrhythmicity related to ASD across all ages and to provide an integrative theoretical framework of their association.
A systematic review of the MEDLINE, PubMed, and Cochrane databases was conducted from November 2018 to February 2019. The search strategies used were MeSH headings and keywords for "sleep-wake circadian rhythms" OR "circadian sleep disorders" OR "sleep-wake pattern" OR "sleep disorders" OR "melatonin" AND "autism spectrum disorder" OR "autism".
One hundred and three studies were identified, 15 regarded circadian sleep dysrhythmicity, 74 regarded sleep disturbances, and 17 regarded melatonin alterations in children and adults with ASD. Our findings suggested that autistic subjects frequently present sleep disturbances in particular short sleep duration, low sleep quality/efficiency, and circadian sleep desynchronization such as delayed phases and/or eveningness. Sleep disturbances and circadian sleep alterations have been related to the severity of autistic symptoms. Genetic studies have shown polymorphisms in circadian CLOCK genes and in genes involved in melatonin pathways in subjects with ASD.
Sleep disturbances and circadian sleep alterations are frequent in subjects with autistic symptoms. These subjects have shown polymorphisms in clock genes expression and in genes involved in melatonin production. The impairment of circadian sleep regulation may increase the individual's vulnerability to develop symptoms of ASD by altering the sleep regulation
, which plays a key role in normal brain development. Even though controversies and "research gaps" are present in literature at this point, we may hypothesize a bidirectional relation between circadian sleep dysfunction and ASD. In particular, circadian sleep dysrhythmicity may predispose to develop ASD symptoms and vice versa within a self-reinforcing feedback loop. By targeting sleep disturbances and circadian sleep dysrhythmicity, we may improve treatment strategies for both children and adults with ASD.
Hypertension and insomnia are very common and often coexist. There is evidence to suggest that the increasing prevalence of arterial hypertension in the past decade might be related both to an ...increased prevalence of insomnia and to the decline of sleep duration due to modern lifestyle. The aim of this paper is to reconsider both the clinical evidence of the relationship between conditions of sleep loss and of perceived impairment in sleep quality with hypertension and the potential pathophysiological mechanisms underlying the biological plausibility of their relationship. Through a systematic search from MEDLINE, EMBASE, PsychINFO we selected articles, which reported experimental sleep deprivation designs, or studied sleep duration or insomnia and their relationship with blood pressure or hypertension in participants over 18 years. This analysis shows that experimental sleep deprivation, short sleep duration, and persistent insomnia are associated with increased blood pressure and increased risk of hypertension, even after controlling for other risk factors. Pathophysiological mechanisms underlying this association might be related to inappropriate arousal ("hyperarousal") due to an overactivation of stress system functions. According this hypothesis, prolonged sleep loss or alterations of sleep quality might act as a neurobiological and physiologic stressor that impair brain functions and contribute to allostatic load, compromising stress resilience and somatic health.
Background:
Several data suggest that coronavirus disease 2019 (COVID-19) pandemic may exacerbate or trigger eating disorders (EDs). The aim of this paper was to summarize current literature studies ...on COVID pandemic and EDs.
Methods:
Literature search, study selection, methods, and quality evaluation were performed according to the preferred reporting items for systematic review and meta-analyses (PRISMA) guidelines.
Results:
A systematic search allowed the initial selection of 172 papers; 21 (12.2%) papers were eligible and included in the review. In selected studies, a total number of 29,108 subjects were enrolled (range: 10–11,391; mean/SD: 1,386 ± 2,800), 6,216 were men (21.4%), 22,703 were women (77.9%), and 189 (0.7%) were gender fluid or not declared. The mean age/SD of subjects was 30.2 ± 7.7. About 12 studies (57.1%) were online surveys, 4 (19.0%) were retrospective studies, 2 (9.5%) were qualitative studies, 2 (9.5%) were longitudinal cohort studies, and 1 was a social media survey (4.8%). Their analysis revealed five main findings: (1) changes in the routines of physical activities were related to the worsening of preoccupation on weight/body shape; (2) food access limitation during pandemic represented the risk factors for both triggering and exacerbating EDs; (3) restriction in healthcare facilities contributed to increase anxiety levels and to modify treatment compliance; (4) social isolation was related to the exacerbation of symptoms in patients with EDs who are home-confined with family members; and (5) conflicts and difficulties in relationships with “no way out” were the maintenance factors for ED symptoms, especially in adolescents and young adults.
Conclusion:
The COVID-19 pandemic had a negative impact on EDs that might be triggered by the exceptional conditions derived from COVID-19-related stress in predisposed subjects. Patients who were already affected by EDs experienced the worsening of their clinical conditions and related quality of life (QoL).
Insomnia symptoms are very common in Bipolar Disorder. Our aim was to assess the potential association between insomnia, emotion dysregulation and suicidality in subjects with Bipolar Disorder.
...Seventy-seven subjects with Bipolar Disorder type II with a depressive episode with mixed features were recruited. Patients were assessed with SCID-DSM-5, the Insomnia Severity Index (ISI), the Difficulties in Emotion Regulation Scale (DERS), the Scale for Suicide Ideation (SSI) while evaluating manic and depressive symptoms.
Subjects with insomnia symptoms compared to those without showed higher scores in the DERS scale and subscales, including impulsivity, and in the SSI scale. Insomnia symptoms significantly predicted the severity of depressive symptoms, emotion dysregulation, and suicidality in subjects with bipolar disorder. In particular, insomnia was related to difficulties in some areas of emotion regulation including impulsivity. Emotion dysregulation significantly mediated the association between insomnia and depressive symptoms (Z = 2.9, p = 0.004). Furthermore, emotional impulsivity mediated the association between insomnia symptoms and suicidality (Z = 2.2, p = 0.03).
In our study, subjects with bipolar disorder suffering from insomnia experienced a greater severity of depressive symptoms and suicidality compared to subjects without insomnia. Insomnia was associated with emotion dysregulation, impulsivity and suicidality. Further research is necessary to investigate if these latter features may benefit from early insomnia treatment in subjects with bipolar disorder.
•Mood disorders constitute a major public health concern: the study of the mechanisms involved should be a priority•In bipolar disorder emotional dysregulation- and suicidality are key factors and insomnia symptoms are frequent.•Subjects with bipolar disorder who suffered from insomnia showed a greater severity of mood symptoms.•In bipolar disorder insomnia was related to emotion dysregulation, impulsivity and to higher suicidality.•Subjects with bipolar disorder may benefit from early insomnia treatment
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