Adjunctive bright light treatment with gradual advance in unipolar major depressive disorder with evening chronotype - A randomized controlled trial.

BACKGROUND: Unipolar non-seasonal depressed patients with concomitant evening chronotype were associated with poor clinical outcomes and higher non-remission rate. This study aims to examine the efficacy of adjunctive bright light therapy with gradual timing advance in a randomized, assessor and prescriber-blinded controlled trial. METHOD: Participants were randomly allocated to receive 5 weeks of either bright white light therapy (BLT) or dim red light (DRL) with the same advancement protocol. Participants were followed up till 5 months after treatment. Primary outcomes included (i) remission rate and (ii) the severity of depression. The analysis was conducted using Kaplan-Meier survival analysis, Cox proportional hazard analysis and linear mixed models. RESULTS: A total of 93 participants (46.4 ± 11.7 years old, 80% female) were randomized. The cumulative remission rate for the BLT and the DRL groups was 67.4% and 46.7%, respectively. Time to remission was shorter for the BLT group relative to the DRL group (log-rank test p = 0.024). Cox proportional hazard survival analysis showed that patients in the BLT group had a higher probability of achieving remission relative to patients in the DRL group [hazard ratio = 1.9 (95% CI = 1.1- 3.4), p = 0.026]. Further sensitivity analysis demonstrated greater improvement in 17-Hamilton Depression Score (group × time interaction, p = 0.04) in the BLT group for those who were adherent to light therapy. CONCLUSIONS: The use of bright light therapy with gradual advance protocol is an effective adjunctive treatment resulting in quicker and a higher rate of remission of depression in patients with non-seasonal unipolar depression and evening-chronotype.

Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.

Caring burden of REM sleep behavior disorder - spouses' health and marital relationship.

OBJECTIVES: Idiopathic REM sleep behavior disorder (iRBD) is noxious due to the high prevalence of sleep-related injuries to patients and their bed-partners. In this study, we aimed to investigate the impact of patients' RBD symptoms on their spouses, in terms of the quality of sleep, and physical, mental and marital aspects. METHOD: A cross-sectional study comparing spouses of iRBD patients to the spouses of the age-and-sex-matched OSAS patients. RESULTS: 40 iRBD patients and their spouses (patients' age 66.6 ± 9.1, male 90%; spouses' age 62.9 ± 7.5), and 35 OSAS patients and their spouses (patients' age 67.8 ± 8.7 years old, male 80%; spouses' age 64.1 ± 9.1) were recruited. Almost all iRBD spouses (90%) reported disturbances by the nocturnal RBD behavioral symptoms of their bedpartners. About two-thirds (62.5%, N = 25) of the iRBD spouses reported a history of being injured during sleep. Spouses of both iRBD and OSAS patients reported a comparably high prevalence of insomnia, anxiety and depressive symptoms. Spouses of iRBD patients, however, reported more impaired quality of life and marital relationship. Nearly two-thirds of RBD couples continued co-sleeping, despite the risk of sleep-related injuries and nocturnal disturbances. CONCLUSIONS: Both iRBD and OSAS spouses exhibited a high prevalence of insomnia and mood problems. In particular, iRBD significantly and negatively affect the spouses' quality of life and the marital relationship. Optimization of iRBD treatment, proper diagnosis, and management of sleep and mental health aspects of spouses may help to lessen the caring burden.

Quality of life and psychosocial issues are important outcome measures in eczema treatment.

BACKGROUND: Atopic eczema (AE) is a common relapsing inflammatory skin disease in children associated with chronicity and poor quality of life. Many children also display depressive, anxiety and stress symptoms. AIM: To investigate the prevalence of depressive, anxiety and stress symptoms, and if these symptoms are associated with disease severity, quality of life and skin biophysiology in childhood AE. METHODS: Psychological symptoms, eczema severity, quality of life and biophysical skin condition of consecutive adolescents at the pediatric dermatology clinic of a teaching hospital were evaluated with the validated Chinese versions of Depressive, Anxiety, Stress Scales (DASS-42), Beck Depression Inventory (BDI-13), Nottingham Eczema Severity Score (NESS), Children's Dermatology Life Quality Index (CDLQI), transepidermal water loss (TEWL) and stratum corneum skin hydration (SH), respectively. RESULTS: AE patients (n=120) had lower SH, higher TEWL, worse CDLQI and reported higher overall, depressive and stress symptom scores, personal history of atopy, current topical corticosteroid usage and food avoidance than non-AE patients (n=26). Depressive, anxiety and stress symptoms were reported in 21%, 33% and 23% of AE patients, respectively. Multivariate analyses showed that these symptoms were significantly correlated with a poor quality of life (partial correlations of 0.40-0.49; p<0.001). Male patients had more severe disease (higher NESS, p=0.036) and DASS-depressive symptoms (multivariate OR=3.2, p=0.034) than females. Patients who reported current topical steroid usage generally practiced food avoidance (p=0.047), had poor quality of life (p=0.043) but less DASS-depression (multivariate OR=0.354, p=0.043). Only 6% of the 120 AE patients reported prior psychology consultation. CONCLUSIONS: Quality of life impairments correlate with disease severity, aberrant skin biophysiology, depression, anxiety and stress symptoms in adolescents with AE. Physicians caring for these patients must evaluate the different but inter-correlated medical, biophysiological and pertinent psychosocial domains. These significant correlations imply that a holistic approach should encompass psychotherapy, behavioral therapy and coping strategies in conjunction with dermatologic therapy.

Pallidal deep brain stimulation: an effective treatment in Chinese patients with tardive dystonia.

Tardive dystonia is an iatrogenic complication of dopamine receptor antagonist medication such as first-generation antipsychotics. It occurs in up to 2% of patients and only 10% recover after stopping medication. Deep brain stimulation for primary dystonia has proven to be effective and its application for secondary dystonias is gaining acceptance. We report our experience in treating three ethnic Chinese schizophrenia patients with severe medically refractory tardive dystonia by globus pallidus internus deep brain stimulation. Preoperatively, all required assistance with essential activities of daily living and two were bed-bound. The mean Burke-Fahn-Marsden Dystonia Rating Scale score was 61 (range, 44-80) and mean Global Dystonia Rating Scale score was 47 (range, 40-52). No procedure-related complications were encountered. By 3 months all could return to unassisted living and walk with support with a mean of 77% and 66% improvement in the Burke-Fahn-Marsden Dystonia Rating Scale and Global Dystonia Rating Scale scores, respectively. Quality-of-life assessment performed for two patients using the EuroQol-5 dimensions visual analogue scale showed a mean improvement of 86% at 3 months. On clinical follow-up, the effect was well maintained for a period of 3 to 10 years. Pallidal deep brain stimulation is a safe and highly effective form of symptomatic treatment for patients with medically refractory tardive dystonia.

Using a partner's facial emotion to elucidate social dominance motivation induced by an SSRI.

Previous studies independently showed that acute treatment with a selective serotonin reuptake inhibitor (SSRI) enhanced happy face recognition, and dominance behaviors which might reflect enhancement of reward sensitivity. The present study aimed to determine whether such a mechanism would be related to social resource acquisition induced by an SSRI. Forty healthy subjects were recruited for the experiment. A randomized, double-blind, placebo-controlled crossover nested within confederate type (happy, fearful, or sad) trial of a single-dose of 10mg escitalopram versus placebo was conducted with a two-week washout period. In each of the treatment groups, the subjects interacted socially with one of the three types of confederate in a waiting room for 3-minute. Then, they went to an individual laboratory and were led to believe that they played the Mixed-motive game with the confederate. The game measures punitive/cooperative behaviors by how participants allocate higher/lower game scores to the confederate and communicate cooperation/ingratiation/helplessness/sadness/blaming/extrapunitive, messages to the confederate. Significant treatment-by-confederate type interactions were observed through game score distributions and ingratiation messages to the confederate and attentive eye gaze. In the happy confederate condition, escitalopram increased ingratiation messages and lowered points awarded to the confederate. In the fearful confederate condition, escitalopram increased ingratiation messages and reduced time spent looking away from the confederate. No changes in these measures were found in the sad confederate condition. Therefore acute escitalopram treatment enhances reward sensitivity to the facial emotions of social partners which in turn increases social resource acquisition and social dominance towards happy but not fearful social partners.

Neurocognitive dysfunction and grey matter density deficit in children with obstructive sleep apnoea.

BACKGROUND: Cerebral structural changes related to obstructive sleep apnoea (OSA) have been reported in adult OSA patients; however, similar data and their associations with neurocognitive dysfunction are scarce in childhood OSA. OBJECTIVE: To compare neurocognitive function, regional grey matter density and cerebral volume in children with and without OSA. METHODS: Fifty OSA cases and 27 normal controls underwent a panel of neurocognitive tests. High resolution 3-dimensional magnetic resonance images of the brain were obtained from 23 OSA cases and 15 gender and age matched controls. Total cerebral volume and regional grey matter density were analyzed using voxel-based morphometry technique and compared between the two groups. Individuals with an obstructive apnoea hypopnoea index (OAHI) > 5 were defined as having moderate-to-severe OSA. RESULTS: Children with OSA showed significantly reduced attention and visual-fine motor coordination scores compared with controls. Grey matter volume deficit was observed in prefrontal and temporal regions of cases with moderate-to-severe OSA only. Significant negative correlations were found between the visual-fine motor coordination score and the ratio of grey matter volume over total brain volume. CONCLUSION: Children with OSA had impaired attention and visual-fine motor coordination. Regional grey matter reduction was evident in children with more severe OSA.

Long sleep duration is associated with higher mortality in older people independent of frailty: a 5-year cohort study.

OBJECTIVES: Although general adult population studies show a U-shaped association between sleep duration and mortality, prolonged rather than short sleep duration was more consistently associated with higher mortality in older populations. Failing health or frailty is a possible mechanism. Thus, we examined the relationship among sleep duration, frailty status, and mortality in an elderly cohort. METHODS: A total of 3427 community-living adults 65 years or older were examined for general health, mood, subjective sleep measures (insomnia, napping, sleep apnea, nighttime sleep duration, sleep medications), frailty, and 5-year mortality. RESULTS: After 5 years, 12.9% of men and 4.5% of women had died. Mean nighttime sleep duration was 7.3 hours. Proportion of participants who slept 10 or more hours increased with increasing frailty. Age-adjusted hazard ratio (HR) for 5-year mortality of long nighttime sleep (≥ 10 hours) was 2.10 (95% confidence interval [CI] 1.33-3.33) in men, and 2.70 (95% CI 0.98-7.46) in women. The HR in men was attenuated (HR 1.75; 95% CI 1.09-2.81) after adjustment for frailty and other covariates, whereas that of women strengthened (HR 2.88; 95% CI 1.01-8.18). Mortality increased sharply with nighttime sleep of 10 hours or more. Nighttime sleep of 10 or more hours (HR 1.75, men; HR 2.88, women) and frailty (HR 2.43, men; HR 2.08, P = .08 in women) were independently associated with 5-year mortality after full adjustment for covariates. CONCLUSION: Frailty and long nighttime sleep duration of 10 or more hours were independently associated with 5-year mortality in older adults.

The association between sleep patterns and obesity in older adults.

BACKGROUND: Reduced sleep duration has been increasingly reported to predict obesity. However, timing and regularity of sleep may also be important. In this study, the cross-sectional association between objectively measured sleep patterns and obesity was assessed in two large cohorts of older individuals. METHODS: Wrist actigraphy was performed in 3053 men (mean age: 76.4 years) participating in the Osteoporotic Fractures in Men Study and 2985 women (mean age: 83.5 years) participating in the Study of Osteoporotic Fractures. Timing and regularity of sleep patterns were assessed across nights, as well as daytime napping. RESULTS: Greater night-to-night variability in sleep duration and daytime napping were associated with obesity independent of mean nocturnal sleep duration in both men and women. Each 1 h increase in the standard deviation of nocturnal sleep duration increased the odds of obesity 1.63-fold (95% confidence interval: 1.31-2.02) among men and 1.22-fold (95% confidence interval: 1.01-1.47) among women. Each 1 h increase in napping increased the odds of obesity 1.23-fold (95% confidence interval: 1.12-1.37) in men and 1.29-fold (95% confidence interval: 1.17-1.41) in women. In contrast, associations between later sleep timing and night-to-night variability in sleep timing with obesity were less consistent. CONCLUSIONS: In both older men and women, variability in nightly sleep duration and daytime napping were associated with obesity, independent of mean sleep duration. These findings suggest that characteristics of sleep beyond mean sleep duration may have a role in weight homeostasis, highlighting the complex relationship between sleep and metabolism.

Rapid eye movement sleep behavior disorder: devising controlled active treatment studies for symptomatic and neuroprotective therapy--a consensus statement from the International Rapid Eye Movement Sleep Behavior Disorder Study Group.

OBJECTIVES: We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD) and related neurodegeneration in RBD. METHODS: The consensus statement was generated during the fourth IRBD-SG symposium in Marburg, Germany in 2011. The IRBD-SG identified essential methodologic components for a randomized trial in RBD, including potential screening and diagnostic criteria, inclusion and exclusion criteria, primary and secondary outcomes for symptomatic therapy trials (particularly for melatonin and clonazepam), and potential primary and secondary outcomes for eventual trials with disease-modifying and neuroprotective agents. The latter trials are considered urgent, given the high conversion rate from idiopathic RBD (iRBD) to Parkinsonian disorders (i.e., PD, dementia with Lewy bodies [DLB], multiple system atrophy [MSA]). RESULTS: Six inclusion criteria were identified for symptomatic therapy and neuroprotective trials: (1) diagnosis of RBD needs to satisfy the International Classification of Sleep Disorders, second edition, (ICSD-2) criteria; (2) minimum frequency of RBD episodes should preferably be ⩾2 times weekly to allow for assessment of change; (3) if the PD-RBD target population is included, it should be in the early stages of PD defined as Hoehn and Yahr stages 1-3 in Off (untreated); (4) iRBD patients with soft neurologic dysfunction and with operational criteria established by the consensus of study investigators; (5) patients with mild cognitive impairment (MCI); and (6) optimally treated comorbid OSA. Twenty-four exclusion criteria were identified. The primary outcome measure for RBD treatment trials was determined to be the Clinical Global Impression (CGI) efficacy index, consisting of a four-point scale with a four-point side-effect scale. Assessment of video-polysomnographic (vPSG) changes holds promise but is costly and needs further elaboration. Secondary outcome measures include sleep diaries; sleepiness scales; PD sleep scale 2 (PDSS-2); serial motor examinations; cognitive indices; mood and anxiety indices; assessment of frequency of falls, gait impairment, and apathy; fatigue severity scale; and actigraphy and customized bed alarm systems. Consensus also was established for evaluating the clinical and vPSG aspects of RBD. End points for neuroprotective trials in RBD, taking lessons from research in PD, should be focused on the ultimate goal of determining the performance of disease-modifying agents. To date no compound with convincing evidence of disease-modifying or neuroprotective efficacy has been identified in PD. Nevertheless, iRBD patients are considered ideal candidates for neuroprotective studies. CONCLUSIONS: The IRBD-SG provides an important platform for developing multinational collaborative studies on RBD such as on environmental risk factors for iRBD, as recently reported in a peer-reviewed journal article, and on controlled active treatment studies for symptomatic and neuroprotective therapy that emerged during the 2011 consensus conference in Marburg, Germany, as described in our report.

Familial aggregation and heritability of insomnia in a community-based study.

BACKGROUND: Emerging data suggested a significant familial aggregation of insomnia. We aimed to clarify the familial aggregation and heritability of insomnia disorder by using structural clinical interviews for the ascertainment of insomnia and psychiatric disorders in a community-based sample. METHODS: Seventy-five adolescents with insomnia and their 180 first degree relatives, together with 141 age- and sex-matched non-insomnia controls and their 382 first degree relatives, were recruited. Each subject underwent a structured clinical interview and completed a series of psychometric inventories. The rates of insomnia disorder among the first degree relatives were employed to analyze familial aggregation. Heritability of insomnia was analyzed by SOLAR program as based on father-mother-offspring trios. RESULTS: Our study confirmed a significant familial aggregation of insomnia with a first degree relatives' recurrence risk of 2.33 for current insomnia and 2.82 for lifetime insomnia, respectively. The heritability±SE of current and lifetime insomnia disorder was 0.48±0.13 and 0.61±0.11 (p<0.001), respectively, which were higher than insomnia symptoms as estimated by the Insomnia Severity Inventory (h(2)±SE=0.27±0.09) and the Pittsburgh Sleep Quality Index (h(2)±SE=0.30±0.11). After exclusion of comorbid psychiatric disorders, the heritability for current and lifetime primary insomnia was 0.45±0.17 (p=0.007) and 0.58±0.21 (p=0.004), respectively. CONCLUSIONS: Our study demonstrates a significant familial aggregation with a high heritability of insomnia disorder. The strong heritability of insomnia persists despite the exclusion of psychiatric disorders. Further molecular genetic investigation of insomnia is indicated.