Isolated dream-enactment behaviours as a prodromal hallmark of rapid eye movement sleep behaviour disorder.

Recurrent dream-enactment behaviours (DEB) and rapid eye movement (REM) sleep without atonia (RSWA) are two diagnostic hallmarks of REM sleep behaviour disorder (RBD), a specific prodrome of α-synucleinopathy. Whilst isolated RSWA (without DEB) was suggested as a prodrome of RBD, the implication of 'isolated' recurrent DEB remains under-investigated. In this cross-sectional study, we sought to investigate neurodegenerative markers amongst the first-degree relatives (FDRs, aged >40 years) of patients with RBD who underwent clinical assessment for DEB, neurodegenerative markers, and video-polysomnography assessment. Isolated recurrent DEB was defined as: (i) three or more episodes of DEB, (ii) had a DEB episode in the past 1 year, and (iii) subthreshold RSWA. We identified 29 FDRs (mean [SD] age 53.4 [8.3] years, 55.2% male) with isolated recurrent DEB and 98 age and sex-matched FDRs as controls. Isolated DEB was associated with nightmare (27.6% versus 11.2%, p = 0.02), and the DEB group had a higher rate of current smoking (27.6% versus 3.1%, p = 0.006), type 2 diabetes mellitus (24.1% versus 10.2%, p = 0.003), anxiety disorder (24.1% versus 11.2%, p = 0.02), and constipation (hard lump of stool, 31.0% versus 7.1%, p < 0.001) than the control group. The present findings revealed that family relatives of patients with RBD with isolated recurrent DEB have increased risk of RBD and neurodegenerative features, which adds to the emerging data that isolated DEB is a prodromal feature of RBD and α-synucleinopathy neurodegeneration.

Causal associations of short and long sleep durations with 12 cardiovascular diseases: linear and nonlinear Mendelian randomization analyses in UK Biobank.

AIMS: Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. METHODS AND RESULTS: Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P < 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P < 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. CONCLUSION: This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.

Rest-Activity Pattern Alterations in Idiopathic REM Sleep Behavior Disorder.

OBJECTIVE: The purpose of this study was to investigate the differences in actigraphy-measured rest-activity patterns (eg, sleep-wake cycle, circadian rest-activity rhythm, and physical activity) across different stages of α-synucleinopathy. METHODS: We compared alterations in 7-day actigraphy-measured rest-activity patterns among patients with clinically diagnosed α-synucleinopathies (n = 44), and their age-, sex-, and body mass index (BMI)-matched patients with idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD, n = 88), and non-rapid eye movement (REM) sleep behavior disorder (RBD) controls (n = 44) in a case-control study (study 1) and between convertors (n = 22) and their age-, sex-, BMI-, iRBD-duration, and follow-up duration-matched non-convertors (n = 66) in a prospective nested case-control study (study 2). RESULTS: In study 1, there were significant increases (all p values were adjusted by false discovery rate < 0.01) in probable napping behaviors (percentage, duration, and episodes), activity fragmentation (estimated by kAR ), and physical inactivity during active periods across controls, and iRBD, to clinically diagnosed α-synucleinopathies. In study 2, higher levels (all p values were adjusted by false discovery rate < 0.05) of baseline objective probable napping, activity fragmentation, and physical inactivity during active periods were associated with the conversion of patients with iRBD into clinically diagnosed α-synucleinopathies at 2 years of follow-up with medium to large effect sizes (Cohen's d: 0.56 to 0.80). These findings were further supported by functional linear modeling analyses. INTERPRETATION: Rest-activity pattern alterations, mainly objective probable napping behaviors, activity fragmentation, and physical inactivity during active period, emerge as early as at the stage of iRBD, which serves as early and robust prodromal markers of the conversion of iRBD into clinically diagnosed α-synucleinopathies. ANN NEUROL 2020;88:817-829.

Chinese self-report version of biological rhythms interview for assessment in neuropsychiatry (C-BRIAN-SR) - psychometric properties and prospective follow-up in patients with non-seasonal depression.

This study examined the psychometric properties and longitudinal changes of the self-reporting Traditional Chinese version of Biological Rhythms Interview for Assessment in Neuropsychiatry (C-BRIAN-SR) among healthy controls (HC) and patients with major depressive episode (MDE). Eighty patients with a current MDE and 80 HC were recruited. Assessments were repeated after two weeks in HC, and upon the discharge of MDE patients to examine the prospective changes upon remission of depression. The C-BRIAN-SR score was significantly higher in the MDE than HC group. The concurrent validity was supported by a positive correlation between scores of C-BRIAN-SR, Insomnia Severity Index and the Hospital Anxiety Depression Scale. C-BRIAN-SR negatively correlated MEQ in the MDE group (r = .30, p = 0.009), suggesting higher rhythm disturbances were associated with a tendency toward eveningness. A moderate test-retest reliability was found (r = .61, p < 0.001). A cut-off of 38.5 distinguished MDE subjects from HC with 82.9% of sensitivity and 81.0% of specificity. C-BRIAN-SR score normalized in remitted MDE patients but remained higher in the non-remitted. The C-BRIAN-SR is a valid and reliable scale for measuring the biological rhythms and may assist in the screening of patients with MDE.

Hypersomnolence is associated with non-remission of major depressive disorder.

OBJECTIVE: This study aimed to investigate the prevalence, clinical correlates and the relationship between hypersomnolence and clinical outcomes in a cohort of MDD patients. METHODS: This is a cross-sectional study of a MDD cohort in an university-affiliated adult psychiatric outpatient clinic. The diagnosis of MDD and severity of depression were ascertained by the clinician with structured clinical interviews. Each participant completed the Epworth Sleepiness Scale (ESS), 1-week sleep diary, and a battery of questionnaires that assessed usual sleep pattern, insomnia, anxiety, depression, fatigue and circadian preference. Hypersomnolence was defined as ESS score ≥14 among those reported ≥7 h of nighttime sleep. Univariate analysis and multiple logistic regression were used to analyze the relationships between the variables. RESULTS: Among 252 recruited subjects, 11 % met the criteria of hypersomnolence as defined by a ESS score ≥14 despite ≥7 h of nighttime sleep. Patients with hypersomnolence had greater depression ratings, higher rates of suicidal ideations over the past week, and more likely to meet a diagnosis of atypical depression (p < 0.05) than those without hypersomnolence. Step-wise logistic regression demonstrated that hypersomnolence was an independent risk factor associated with a 3-fold increase in the risk of depression non-remission (adjusted OR 3.13; 95 % CI 1.10-8.95; p = 0.034). CONCLUSION: Patients with hypersomnolence despite seemingly adequate sleep represent a subgroup of MDD patients who have a more severe illness profile with higher non-remission rate and suicidality. The findings highlight the importance of addressing both sleep and mood symptoms in the management of MDD.

Attenuated melanopsin-mediated post-illumination pupillary response (PIPR) is associated with reduced actigraphic amplitude and mesor in older adults.

STUDY OBJECTIVES: This study aimed to explore the relationship between post-illumination pupillary response (PIPR) with sleep and circadian measures in a community sample of healthy older adults. METHODS: Eligible participants were invited to complete a one-week sleep diary, actigraphy and provide an overnight urine sample to measure urinary 6-sulfatoxymelatonin (aMT6s). PIPR was defined as the as the pupil constriction at 6s post-stimulus (PIPR-6s), and ii) for 30s beginning 10s after stimulus (PIPR-30s) normalized as a percentage to the baseline pupil diameter, after 1s of blue and 1s of red-light stimulus, respectively. The Net-PIPRs were reported by subtracting the PIPR to red stimulus from the PIPR to blue stimulus. The relationship between PIPR metrics to aMT6s and actigraphic rest-activity rhythm parameters was examined by generalized linear models. RESULTS: A total of 48 participants were recruited (Mean age: 62.6 ± 7.1 years, Male: 44%). Both Net PIPR-6s and Net PIPR-30s were significantly associated with actigraphic rest-activity amplitude (B=0.03, p=0.001 and B=0.03, p=0.01, respectively), and actigraphic rest-activity mesor (B=0.02, p=0.001 and B=0.03, p=0.004, respectively). Additionally, the Net PIPR-30s were positively associated with overnight aMT6s level (B=0.04, p=0.03), and negatively associated with actigraphic rest-activity acrophase (B=-0.01, p=0.004) in the fully adjusted models. CONCLUSION: Attenuated PIPR is associated with a reduced actigraphic amplitude and mesor. The reduced retinal light responsivity may be a potential pathway contributing to impaired photic input to the circadian clock and resulted in the age-related circadian changes in older adults.

Chronic post-COVID neuropsychiatric symptoms persisting beyond one year from infection: a case-control study and network analysis.

Our study aims to delineate the phenotypes of chronic neuropsychiatric symptoms among adult subjects recovering from their first COVID that occurred more than one year ago. We also aim to explore the clinical and socioeconomic risk factors of having a high loading of chronic neuropsychiatric symptoms. We recruited a post-COVID group who suffered from their first pre-Omicron COVID more than a year ago, and a control group who had never had COVID. The subjects completed app-based questionnaires on demographic, socioeconomic and health status, a COVID symptoms checklist, mental and sleep health measures, and neurocognitive tests. The post-COVID group has a statistically significantly higher level of fatigue compared to the control group (p < 0.001). Among the post-COVID group, the lack of any COVID vaccination before the first COVID and a higher level of material deprivation before the COVID pandemic predicts a higher load of chronic post-COVID neuropsychiatric symptoms. Partial correlation network analysis suggests that the chronic post-COVID neuropsychiatric symptoms can be clustered into two major (cognitive complaints -fatigue and anxiety-depression) and one minor (headache-dizziness) cluster. A higher level of material deprivation predicts a higher number of symptoms in both major clusters, but the lack of any COVID vaccination before the first COVID only predicts a higher number of symptoms in the cognitive complaints-fatigue cluster. Our result suggests heterogeneity among chronic post-COVID neuropsychiatric symptoms, which are associated with the complex interplay of biological and socioeconomic factors.

Clinical and neuroimaging markers of neurodegeneration in first-degree relatives of patients with REM sleep behavior disorder with and without isolated rapid eye movement sleep without atonia: A case-control clinical and dopamine PET study.

OBJECTIVES: The current study aimed to examine the neurodegenerative implication of isolated REM sleep without atonia (RSWA) among first-degree relatives of patients with REM sleep behaviour disorder (RBD). METHODS: This cross-sectional case-control study recruited three groups of subjects: First-degree relatives of RBD patients with isolated RSWA (n = 17), first-degree relatives of RBD patients without isolated RSWA (n = 18), and normal controls who did not have any RWSA and family history of RBD (n = 15). Prodromal Parkinson's Disease likelihood ratio by the updated MDS Research Criteria and striatal dopaminergic transmission function of the subjects as assessed by triple-tracer (18F-DOPA, 11C-Raclopride, and 18F-FDG) PET/CT scan were used as proxy markers of neurodegeneration. RESULTS: In contrary to our hypothesis, the three groups did not differ in their pre- or post-striatal dopaminergic transmission function, and their Prodromal Parkinson's Disease likelihood ratio. However, they differed significantly in their frequency of a having first-degree relatives with Parkinson's disease or dementia of Lewy body (first-degree relativess with RSWA vs first degree relatives without RSWA vs normal controls = 58.8% vs 22.2% vs 0%, p = 0.001). CONCLUSION: FDRs of RBD patients with isolated RSWA did not have increased neurodegenerative markers compared to FDRs of RBD patients without isolated RSWA and normal control, despite an paradoxical increase in frequency of Parkinson's disease or dementia of Lewy body among their family compared to FDRs of RBD patients without isolated RSWA. Further longitudinal follow-up study will be needed to ascertain their long-term prognosis.

Epidemiology, Symptomatology, and Risk Factors for Long COVID Symptoms: Population-Based, Multicenter Study.

BACKGROUND: Long COVID induces a substantial global burden of disease. The pathogenesis, complications, and epidemiological and clinical characteristics of patients with COVID-19 in the acute phase have been evaluated, while few studies have characterized the epidemiology, symptomatology, and risk factors of long COVID symptoms. Its characteristics among patients with COVID-19 in the general population remain unaddressed. OBJECTIVE: We examined the prevalence of long COVID symptoms, its symptom patterns, and its risk factors in 4 major Chinese cities in order to fill the knowledge gap. METHODS: We performed a population-based, multicenter survey using a representative sampling strategy via the Qualtrics platform in Beijing, Shanghai, Guangzhou, and Hong Kong in June 2022. We included 2712 community-dwelling patients with COVID-19 and measured the prevalence of long COVID symptoms defined by the World Health Organization (WHO), and their risk factors. The primary outcomes were the symptoms of long COVID, with various levels of impact. A descriptive analysis of the prevalence and distribution of long COVID symptoms according to disease severity was conducted. A sensitivity analysis of increasing the number of long COVID symptoms was also conducted. Univariate and multivariate regression analyses were performed to examine the risk factors of severe long COVID symptoms, including age, gender, marital status, current occupation, educational level, living status, smoking habits, monthly household income, self-perceived health status, the presence of chronic diseases, the use of chronic medication, COVID-19 vaccination status, and the severity of COVID-19. RESULTS: The response rate was 63.6% (n=2712). The prevalence of long COVID, moderate or severe long COVID, and severe long COVID was 90.4% (n=2452), 62.4% (n=1692), and 31.0% (n=841), respectively. Fatigue (n=914, 33.7%), cough (n=865, 31.9%), sore throat (n=841, 31.0%), difficulty in concentrating (n=828, 30.5%), feeling of anxiety (n=817, 30.2%), myalgia (n=811, 29.9%), and arthralgia (n=811, 29.9%) were the most common severe long COVID symptoms. From multivariate regression analysis, female gender (adjusted odds ratio [aOR]=1.49, 95% CI 1.13-1.95); engagement in transportation, logistics, or the discipline workforce (aOR=2.52, 95% CI 1.58-4.03); living with domestic workers (aOR=2.37, 95% CI 1.39-4.03); smoking (aOR=1.55, 95% CI 1.17-2.05); poor or very poor self-perceived health status (aOR=15.4, 95% CI 7.88-30.00); ≥3 chronic diseases (aOR=2.71, 95% CI 1.54-4.79); chronic medication use (aOR=4.38, 95% CI 1.66-11.53); and critical severity of COVID-19 (aOR=1.52, 95% CI 1.07-2.15) were associated with severe long COVID. Prior vaccination with ≥2 doses of COVID-19 vaccines was a protective factor (aOR=0.35-0.22, 95% CI 0.08-0.90). CONCLUSIONS: We examined the prevalence of long COVID symptoms in 4 Chinese cities according to the severity of COVID-19. We also evaluated the pattern of long COVID symptoms and their risk factors. These findings may inform early identification of patients with COVID-19 at risk of long COVID and planning of rehabilitative services.

Effects of cumulative COVID-19 cases on mental health: Evidence from multi-country survey.

BACKGROUND: Depression and anxiety were both ranked among the top 25 leading causes of global burden of diseases in 2019 prior to the coronavirus disease 2019 (COVID-19) pandemic. The pandemic affected, and in many cases threatened, the health and lives of millions of people across the globe and within the first year, global prevalence of anxiety and depression increased by 25% with the greatest influx in places highly affected by COVID-19. AIM: To explore the psychological impact of the pandemic and resultant restrictions in different countries using an opportunistic sample and online questionnaire in different phases of the pandemic. METHODS: A repeated, cross-sectional online international survey of adults, 16 years and above, was carried out in 10 countries (United Kingdom, India, Canada, Bangladesh, Ukraine, Hong Kong, Pakistan, Egypt, Bahrain, Saudi Arabia). The online questionnaire was based on published approaches to understand the psychological impact of COVID-19 and the resultant restrictions. Five standardised measures were included to explore levels of depression [patient health questionnaire (PHQ-9)], anxiety [generalized anxiety disorder (GAD) assessment], impact of trauma [the impact of events scale-revised (IES-R)], loneliness (a brief loneliness scale), and social support (The Multi-dimensional Scale of Perceived Social support). RESULTS: There were two rounds of the online survey in 10 countries with 42866 participants in Round 1 and 92260 in Round 2. The largest number of participants recruited from the United Kingdom (112985 overall). The majority of participants reported receiving no support from mental health services throughout the pandemic. This study found that the daily cumulative COVID-19 cases had a statistically significant effect on PHQ-9, GAD-7, and IES-R scores. These scores significantly increased in the second round of surveys with the ordinary least squares regression results with regression discontinuity design specification (to control lockdown effects) confirming these results. The study findings imply that participants' mental health worsened with high cumulative COVID-19 cases. CONCLUSION: Whist we are still living through the impact of COVID-19, this paper focuses on its impact on mental health, discusses the possible consequences and future implications. This study revealed that daily cumulative COVID-19 cases have a significant impact on depression, anxiety, and trauma. Increasing cumulative cases influenced and impacted education, employment, socialization and finances, to name but a few. Building a database of global evidence will allow for future planning of pandemics, particularly the impact on mental health of populations considering the cultural differences.

Prediction of Dropout in a Randomized Controlled Trial of Adjunctive Light Treatment in Patients with Non-Seasonal Depression and Evening Chronotype.

The current study examined the possible predictors of dropout during a five-week light treatment (LT) with a gradual advance protocol in 93 patients with unipolar non-seasonal depression and evening chronotypes by comparing their clinical characteristics and performing a logistic regression analysis. Nineteen out of ninety-three (20%) subjects (80% female, 46.5 ± 11.7 years old) dropped out during the 5-week light treatment. Treatment non-adherence (i.e., receiving LT for less than 80% of the prescribed duration) over the first treatment week predicted a five-fold increase in risk of dropout during light therapy (OR: 5.85, CI: 1.41-24.21) after controlling for potential confounders, including age, gender, treatment group, rise time at the baseline, patient expectation, and treatment-emergent adverse events. There is a need to incorporate strategies to enhance treatment adherence and retention in both research and clinical settings. Chinese clinical trial registry (ChiCTR-IOR-15006937).

Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference.

STUDY OBJECTIVES: Eveningness is associated with worse outcomes in depression. It remained unclear if eveningness could be altered with chronobiological therapy and whether such a change would predict long-term outcomes of depression. METHODS: Data from a randomized controlled trial of 5-week adjunctive bright light therapy with a gradual advance protocol conducted in 91 adult patients with nonseasonal unipolar depression and eveningness (Morningness-Eveningness Questionnaire, score ≤ 41) was examined. "Change of eveningness" was defined by Morningness-Eveningness Questionnaire score over 41 at posttreatment week 5 and "persistent change of eveningness" was defined as maintenance of Morningness-Eveningness Questionnaire score > 41 throughout the follow-up period from week 5 to posttreatment 5 months. RESULTS: Thirty-three participants (36%) had change of eveningness at week 5. Generalized estimating equations models showed that a change of eveningness at week 5 predicted a 2-fold increase in remission of depression over the 5-month follow up (odds ratio = 2.61 95% confidence interval 1.20-5.71, P = .016). Twenty-five participants (75.7%) had a persistent change and were more likely to achieve a remission of depression over the 5-month follow up (odds ratio = 3.18, 95% confidence interval: 1.35-7.50, P = .008). CONCLUSIONS: One-third of the patients with depression changed their evening-preference after 5-week of chronotherapeutic treatment, and such change predicted a higher likelihood of depression remission over 5 months of follow-up. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Registry; Name: Adjunctive light treatment in major depressive disorder patients with evening chronotype-A randomized controlled trial; URL: https://www.chictr.org.cn/showprojen.aspx?proj=11672; Identifier: ChiCTR-IOR-15006937. CITATION: Chan JWY, Chan NY, Li SX, et al. Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference. J Clin Sleep Med. 2022;18(2):523-531.

Night Shift Work, MTNR1B rs10830963 Polymorphism, and Prostate Cancer Risk: Findings from a Prospective, Population-Based Study.

BACKGROUND: The association between night shift work and prostate cancer is controversial. Evidence shows that genetic and environmental factors both contribute to the development of prostate cancer. It is well known that melatonin plays a protective role in prostate cancer. Melatonin receptor 1B gene (MTNR1B) rs10830963 influences the dynamics of melatonin secretion, and night shift work, which disrupts our internal circadian rhythms, also dysregulates the production of melatonin. Therefore, we aimed to examine the interaction between night shift work and rs10830963 polymorphism on prostate cancer. METHODS: This is a prospective cohort study based on UK Biobank that included 133,416 employed male participants. Exposures included night shift work and rs10830963 polymorphism. The primary outcome was the incidence of prostate cancer. Cox regression analysis was used to estimate the association of night shift work and MTNR1B rs10830963 with prostate cancer. RESULTS: A significant interaction was found between night shift work and MTNR1B rs10830963 on the incidence of prostate cancer (P = 0.009). Among non-night shift workers, rs10830963 polymorphism was not significantly associated with the risk of prostate cancer. Among night shift workers, compared with CC carriers, GC carriers had a significantly lower risk of prostate cancer [HR: 0.69; 95% confidence interval (CI): 0.51-0.93], and similar associations were more evident for GG carriers (HR: 0.33; 95% CI: 0.15-0.75). CONCLUSIONS: Compared with MTNR1B rs10830963 CC, carrying allele G may reduce the risk of prostate cancer when exposed to night shift work. IMPACT: These results suggest that rs10830963 G carriers may have a lower risk of prostate cancer when taking night shifts.

High prevalence of hypokalemia in acute psychiatric inpatients.

BACKGROUND: Hypokalemia is an easily identifiable, clinically important but commonly neglected condition in psychiatric patients. This study intended to examine the prevalence of hypokalemia and its clinical correlates in acute psychiatric inpatients. METHOD: This retrospective study was conducted over a 6 month period in 2008. The case notes, computerized records and laboratory results of all patients who were consecutively admitted to the acute psychiatric wards in a University-affiliated regional psychiatric unit were studied. RESULT: Three hundred forty-seven patients out of 440 admissions were studied. Hypokalemia, as defined by serum potassium level of less than 3.5 mmol/L, was found in 20.5% of patients with a higher prevalence in psychotic patients (27.7%). The mean potassium level of psychotic patients was lower than that of the overall study population (3.72 vs. 3.81 mmol/L, P<.05). White cell counts among the hypokalemic patients were higher than those without hypokalemia (7.8 vs. 7.1 x 10(9)/L, P=.02). CONCLUSION: Hypokalemia was common among acute psychiatric inpatients. Both agitation and the use of antipsychotics were postulated to contribute to the high prevalence of hypokalemia among acutely ill psychiatric patients.