Altered Impulsivity Across Drug-Naïve Parkinsonism, Isolated Rapid Eye Movement Sleep Behavior Disorder, and Their High-Risk Relatives.

OBJECTIVE: To determine multidimensional impulsivity levels across different early stages of α-synucleinopathy. METHODS: This cross-sectional study investigated motor and decisional impulsivity levels using a panel of computerized tasks among drug-naïve parkinsonism patients, isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) patients and their first-degree relatives (iRBD-FDRs), and control participants. Trait impulsivity and impulse control behaviors were assessed by self-reported questionnaires. RESULTS: A total of 27 drug-naïve parkinsonism patients, 157 iRBD patients, 66 iRBD-FDRs, and 82 control participants were recruited. Parkinsonism and iRBD patients had fewer numbers of extracted beads in beads task 1 and 2 (both p < 0.001), and a higher rate of irrational choice in task 1 (p = 0.046) before making decisions, and fewer numbers of pumps of unexploded blue balloons in the balloon analog risk task (p = 0.004) than control participants, indicating a higher level of reflection impulsivity and a lower level of risk taking, respectively. iRBD patients had more no-go errors in the go/no-go task than control participants (padjusted = 0.036), suggesting a higher level of motor impulsivity. iRBD-FDRs with dream-enactment behaviors had fewer numbers of extracted beads (p = 0.047) in beads task 2 than FDRs without dream-enactment behaviors, suggesting a possible higher level of reflection impulsivity. INTERPRETATION: A complex construct of altered impulsivity with decreased risk taking, but increased reflection and motor impulsivity, has already occurred at the prodromal and early stages of α-synucleinopathy, which have implications for underlying pathophysiology and clinical management of α-synucleinopathy, especially for impulse control behaviors upon dopaminergic drug treatment. ANN NEUROL 2024;95:544-557.

Visuospatial dysfunction predicts dementia-first phenoconversion in isolated REM sleep behaviour disorder.

OBJECTIVE: While isolated rapid eye movement sleep behaviour disorder (iRBD) is known as a prodrome of α-synucleinopathies, the prediction for its future phenoconversion to parkinsonism-first or dementia-first subtype remains a challenge. This study aimed to investigate whether visuospatial dysfunction predicts dementia-first phenoconversion in iRBD. METHODS: Patients with iRBD and control subjects were enrolled in this prospective cohort study. Baseline neuropsychological assessment included the Unified Parkinson's Disease Rating Scale part III, Montreal Cognitive Assessment (MoCA), Rey-Osterrieth complex figure (ROCF), Colour Trails test (CTT), Farnsworth-Munsell 100-hue test and Digit Span test. The anterior and posterior subscores of MoCA as well as their modified versions were explored. A composite score derived from ROCF and CTT was also explored. Regular follow-up was conducted to determine the phenoconversion status of iRBD patients. RESULTS: The study included 175 iRBD patients and 98 controls. During a mean follow-up of 5.1 years, 25.7% of patients experienced phenoconversion. Most of the neuropsychological tests could differentiate dementia-first but not parkinsonism-first convertors from non-convertors. The modified posterior subscore of MoCA, by integrating the Alternating Trail Making and Clock Drawing components into original the posterior subscore, which mainly reflects visuospatial function, was the strongest predictor for dementia-first phenoconversion (adjusted HR 5.48, 95% CI 1.67 to 17.98). CONCLUSION: Visuospatial dysfunction, as reflected mainly by the modified posterior subscore of MoCA, is a predictive factor for dementia-first phenoconversion in iRBD, suggesting its potential for being a biomarker for clinical prognostic prediction and potential neuroprotective trials aiming to delay or prevent dementia.

Familial α-synucleinopathy spectrum features in patients with psychiatric REM sleep behaviour disorder.

BACKGROUND: Rapid eye movement (REM) sleep behaviour disorder (RBD) is one of the earliest and most specific prodromes of the α-synucleinopathies including Parkinson's disease (PD). It remains uncertain whether RBD occurring in the context of psychiatric disorders (psy-RBD), although very common, is merely a benign epiphenomenon of antidepressant treatment, or whether it harbours an underlying α-synucleinopathy. We hypothesised that patients with psy-RBD demonstrate a familial predisposition to an α-synucleinopathy. METHODS: In this case-control-family study, a combination of family history and family study method was used to measure the α-synucleinopathy spectrum features, which included RBD, neurodegenerative prodromal markers and clinical diagnoses of neurodegenerative disorders. We compared the risk of α-synucleinopathy spectrum features in the first-degree relatives (FDRs) of patients with psy-RBD, psychiatric controls and healthy controls. RESULTS: There was an increase of α-synucleinopathy spectrum features in the psy-RBD-FDRs, including possible and provisional RBD (adjusted HR (aHR)=2.02 and 6.05, respectively), definite RBD (adjusted OR=11.53) and REM-related phasic electromyographic activities, prodromal markers including depression (aHR=4.74) and probable subtle parkinsonism, risk of prodromal PD and clinical diagnosis of PD/dementia (aHR=5.50), as compared with healthy-control-FDRs. When compared with psychiatric-control-FDRs, psy-RBD-FDRs consistently presented with a higher risk for the diagnosis and electromyographic features of RBD, diagnosis of PD/dementia (aHR=3.91) and risk of prodromal PD. In contrast, psychiatric controls only presented with a familial aggregation of depression. CONCLUSION: Patients with psy-RBD are familially predisposed to α-synucleinopathy. The occurrence of RBD with major depression may signify a subtype of major depressive disorders with underlying α-synucleinopathy neurodegeneration. TRIAL REGISTRATION NUMBER: NCT03595475.

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.

Prevalence and correlates of REM sleep behaviour disorder in patients with major depressive disorder: a two-phase study.

OBJECTIVE: To investigate the prevalence and clinical correlates of video polysomnography (vPSG)-confirmed rapid eye movement sleep behaviour disorder (RBD) in patients with major depressive disorder (MDD). METHODS: This is a clinic-based two-phase epidemiological study. In phase 1, patients with MDD were screened by a validated questionnaire, RBD Questionnaire-Hong Kong (RBDQ-HK). In phase 2, a subsample of both the screen-positive (RBDQ-HK >20) and screen-negative patients with MDD underwent further clinical and sleep assessment (vPSG) to confirm the diagnosis of RBD (MDD+RBD). Poststratification weighting method was used to estimate the prevalence of MDD+RBD. The total likelihood ratio and the probability of prodromal Parkinson's disease (PD) were calculated from prodromal markers and risk factors, as per the Movement Disorder Society research criteria. RESULTS: A total of 455 patients with MDD were screened (median age (IQR)=52.66 (15.35) years, 77.58% woman, 43.74% positive). Eighty-one patients underwent vPSG and 12 of them were confirmed MDD+RBD. The prevalence of MDD+RBD was estimated to be 8.77% (95% CI: 4.33% to 16.93%), with possibly male predominance. MDD+RBD were associated with colour vision and olfaction deficit and a higher probability for prodromal PD. CONCLUSIONS: Almost 9% of patients with MDD in the psychiatric outpatient clinic has vPSG-confirmed RBD. Comorbid MDD+RBD may represent a subtype of MDD with underlying α-synucleinopathy neurodegeneration. Systematic screening of RBD symptoms and necessity of vPSG confirmation should be highlighted for capturing this MDD subtype with a view to enhance personalised treatment and future neuroprotection to prevent neurodegeneration.

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.

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.

History for some or lesson for all? A systematic review and meta-analysis on the immediate and long-term mental health impact of the 2002-2003 Severe Acute Respiratory Syndrome (SARS) outbreak.

BACKGROUND: The aims of this systematic review and meta-analysis are to examine the prevalence of adverse mental health outcomes, both short-term and long-term, among SARS patients, healthcare workers and the general public of SARS-affected regions, and to examine the protective and risk factors associated with these mental health outcomes. METHODS: We conducted a systematic search of the literature using databases such as Medline, Pubmed, Embase, PsycInfo, Web of Science Core Collection, CNKI, the National Central Library Online Catalog and dissertation databases to identify studies in the English or Chinese language published between January 2003 to May 2020 which reported psychological distress and mental health morbidities among SARS patients, healthcare workers, and the general public in regions with major SARS outbreaks. RESULTS: The literature search yielded 6984 titles. Screening resulted in 80 papers for the review, 35 of which were included in the meta-analysis. The prevalence of post-recovery probable or clinician-diagnosed anxiety disorder, depressive disorder, and post-traumatic stress disorder (PTSD) among SARS survivors were 19, 20 and 28%, respectively. The prevalence of these outcomes among studies conducted within and beyond 6 months post-discharge was not significantly different. Certain aspects of mental health-related quality of life measures among SARS survivors remained impaired beyond 6 months post-discharge. The prevalence of probable depressive disorder and PTSD among healthcare workers post-SARS were 12 and 11%, respectively. The general public had increased anxiety levels during SARS, but whether there was a clinically significant population-wide mental health impact remained inconclusive. Narrative synthesis revealed occupational exposure to SARS patients and perceived stigmatisation to be risk factors for adverse mental health outcomes among healthcare workers, although causality could not be determined due to the limitations of the studies. CONCLUSIONS: The chronicity of psychiatric morbidities among SARS survivors should alert us to the potential long-term mental health complications of covid-19 patients. Healthcare workers working in high-risk venues should be given adequate mental health support. Stigmatisation against patients and healthcare workers should be explored and addressed. The significant risk of bias and high degree of heterogeneity among included studies limited the certainty of the body of evidence of the review.

Cultural variations in wellbeing, burnout and substance use amongst medical students in twelve countries.

High levels of stress, burnout, and symptoms of poor mental health have been well known among practicing doctors for a number of years. Indeed, many health systems have formal and informal mechanisms to offer support and treatment where needed, though this varies tremendously across cultures. There is increasing evidence that current medical students, our doctors of the future, also report very high levels of distress, burnout, and substance misuse. We sampled large groups of medical students in 12 countries at the same time and with exactly the same method in order to aid direct comparison. 3766 students responded to our survey across five continents in what we believe is a global first. Our results show that students in all 12 countries report very high levels of 'caseness' on validated measures of psychiatric symptoms and burnout. Rates of substance misuse, often a cause of or coping mechanism for this distress, and identified sources of stress also varied across cultures. Variations are strongly influenced by cultural factors. Further quantitative and qualitative research is required to confirm our results and further delineate the causes for high rates of psychiatric symptoms and burnout. Studies should also focus on the implementation of strategies to safeguard and identify those most at risk.

Development of a Cost-Effective Surgical Headlight Using Consumer Light Emitting Diode Lighting and 3D Printing.

Need. Battery-powered Light Emitting Diode (LED) surgical headlights are necessary for improved intraoperative illumination but may be costly. Technical Solution. The objective of this study was to develop a low-cost surgical headlight using a consumer-grade LED headlight and 3D-printed mount. Proof of Concept. Eighteen surgical residents performed simulation exercises that mimicked suturing in the oral cavity using both a custom prototype headlight and a commercial surgical headlight. The time required to complete the task with each headlight was recorded along with an exit survey. A second device was created based on the critiques of the first device and was tested by ten additional surgical trainees. Surgical residents completed the simulation task in 27 ± 8.6 seconds and 21 ± 5.6 seconds with the commercially available headlight and first prototype, respectively. In the second experiment, the simulation task was completed in 23 ± 11.1 and 23 ± 12.2 seconds with the commercially available headlight and second device, respectively. Survey results showed an overall positive consensus, with critiques about headband security, suggestions for smaller LED chassis, and a more robust mounting bracket. Some preferred the prototype headlight due to the wider field of illumination compared to the commercially available unit (ie, beam spread/beam angle). Next Steps. Future adjustments are required to optimize the location of the headlight and the battery to modify the weight distribution of the device. Conclusion. These findings demonstrate that our prototype models are viable alternatives to conventional surgical headlights and warrant continued optimization for broader adoption by surgeons and trainees for whom higher-cost alternatives are not an option.

Residual Injurious Symptoms and Its Association With Neurodegenerative Outcomes in Idiopathic Rapid Eye Movement Sleep Behavior Disorder: A Retrospective, Longitudinal Follow-up Study.

BACKGROUND: The risk of neurodegenerative disorders in idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with residual injurious symptoms (RIS) after symptomatic treatment with clonazepam and/or melatonin is unclear. OBJECTIVE: The objective of this study was to determine the rate and correlates of RIS and its association with the risk of neurodegenerative diseases in patients with iRBD. METHODS: This was a retrospective cohort study. RIS was defined by the RBD Questionnaire-Hong Kong (RBDQ-HK) as the presence of residual sleep-related injuries or potential injurious behaviors for at least once a month after at least 1 year of treatment. RESULTS: A total of 15 out of 133 (11.3%) patients with iRBD (age at diagnosis = 66.5 ± 7.3 years, 77.4% male) had RIS after 2.7 years of treatment. Patients with RIS were younger at both onset and polysomnography-confirmed diagnosis of iRBD (years, mean ± standard deviation, 56.3 ± 6.9 vs. 61.8 ± 7.6, P = 0.01; 61.2 ± 4.2 vs. 67.2 ± 7.4, P < 0.001, respectively), had more severe behavioral symptoms at diagnosis (both RBDQ-HK total score and behavioral subscore, P = 0.01), and used a higher maximum dose of clonazepam (mg; median [interquartile range], 1.5 [1.0] vs. 1.0 [1.0], P = 0.01). RIS was probably associated with a higher risk of developing dementia with Lewy bodies (adjusted hazard ratio [95% confidence interval], 5.47 [1.71-17.46], adjusted for onset age of RBD), but not Parkinsons's disease in the follow-up. CONCLUSION: RIS is not uncommon in patients with iRBD despite long-term medication treatment. An earlier onset and more severe clinical profile are associated with RIS. The prediction of RIS toward dementia with Lewy bodies but not PD suggests that RIS may probably help to identify the specific risk of different subtypes of α-synucleinopathy. © 2020 International Parkinson and Movement Disorder Society.

Wellbeing and mental health amongst medical students from Hong Kong.

Medical students are a known high-risk group for mental health issues. This study aimed to survey the psychological well-being of medical students from Hong Kong, a known stressful city. This study is part of a wider effort to compare the psychological well-being of medical students world-wide. We invited medical students from Hong Kong to complete a self-report questionnaire online. The questionnaire included questions on demographics, known mental health issues, sources of psychological stress, and substance use. It also included the cut-annoyed-guilty-eye (CAGE) questionnaire, Short-Form General Health Questionnaire (GHQ-12), and the Oldenburg Burnout Inventory (OLBI). There were 123 responses. Our results suggest high levels of psychological morbidity and distress among medical students in Hong Kong. 87% screened positive for minor psychiatric disorders on the GHQ-12 and 95% met OLBI thresholds for burnout. Female respondents demonstrated significantly higher mean GHQ-12 scores than male. Despite the apparent high prevalence of mental ill-health in this population, only 15% of respondents reported receiving professional help.

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.

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.

Multimodal digital assessment of depression with actigraphy and app in Hong Kong Chinese.

There is an emerging potential for digital assessment of depression. In this study, Chinese patients with major depressive disorder (MDD) and controls underwent a week of multimodal measurement including actigraphy and app-based measures (D-MOMO) to record rest-activity, facial expression, voice, and mood states. Seven machine-learning models (Random Forest [RF], Logistic regression [LR], Support vector machine [SVM], K-Nearest Neighbors [KNN], Decision tree [DT], Naive Bayes [NB], and Artificial Neural Networks [ANN]) with leave-one-out cross-validation were applied to detect lifetime diagnosis of MDD and non-remission status. Eighty MDD subjects and 76 age- and sex-matched controls completed the actigraphy, while 61 MDD subjects and 47 controls completed the app-based assessment. MDD subjects had lower mobile time (P = 0.006), later sleep midpoint (P = 0.047) and Acrophase (P = 0.024) than controls. For app measurement, MDD subjects had more frequent brow lowering (P = 0.023), less lip corner pulling (P = 0.007), higher pause variability (P = 0.046), more frequent self-reference (P = 0.024) and negative emotion words (P = 0.002), lower articulation rate (P < 0.001) and happiness level (P < 0.001) than controls. With the fusion of all digital modalities, the predictive performance (F1-score) of ANN for a lifetime diagnosis of MDD was 0.81 and 0.70 for non-remission status when combined with the HADS-D item score, respectively. Multimodal digital measurement is a feasible diagnostic tool for depression in Chinese. A combination of multimodal measurement and machine-learning approach has enhanced the performance of digital markers in phenotyping and diagnosis of MDD.

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.

A synbiotic preparation (SIM01) for post-acute COVID-19 syndrome in Hong Kong (RECOVERY): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Post-acute COVID-19 syndrome (PACS) affects over 65 million individuals worldwide but treatment options are scarce. We aimed to assess a synbiotic preparation (SIM01) for the alleviation of PACS symptoms. METHODS: In this randomised, double-blind, placebo-controlled trial at a tertiary referral centre in Hong Kong, patients with PACS according to the US Centers for Disease Control and Prevention criteria were randomly assigned (1:1) by random permuted blocks to receive SIM01 (10 billion colony-forming units in sachets twice daily) or placebo orally for 6 months. Inclusion criterion was the presence of at least one of 14 PACS symptoms for 4 weeks or more after confirmed SARS-CoV-2 infection, including fatigue, memory loss, difficulty in concentration, insomnia, mood disturbance, hair loss, shortness of breath, coughing, inability to exercise, chest pain, muscle pain, joint pain, gastrointestinal upset, or general unwellness. Individuals were excluded if they were immunocompromised, were pregnant or breastfeeding, were unable to receive oral fluids, or if they had received gastrointestinal surgery in the 30 days before randomisation. Participants, care providers, and investigators were masked to group assignment. The primary outcome was alleviation of PACS symptoms by 6 months, assessed by an interviewer-administered 14-item questionnaire in the intention-to-treat population. Forward stepwise multivariable logistical regression was performed to identify predictors of symptom alleviation. The trial is registered with ClinicalTrials.gov, NCT04950803. FINDINGS: Between June 25, 2021, and Aug 12, 2022, 463 patients were randomly assigned to receive SIM01 (n=232) or placebo (n=231). At 6 months, significantly higher proportions of the SIM01 group had alleviation of fatigue (OR 2·273, 95% CI 1·520-3·397, p=0·0001), memory loss (1·967, 1·271-3·044, p=0·0024), difficulty in concentration (2·644, 1·687-4·143, p<0·0001), gastrointestinal upset (1·995, 1·304-3·051, p=0·0014), and general unwellness (2·360, 1·428-3·900, p=0·0008) compared with the placebo group. Adverse event rates were similar between groups during treatment (SIM01 22 [10%] of 232 vs placebo 25 [11%] of 231; p=0·63). Treatment with SIM01, infection with omicron variants, vaccination before COVID-19, and mild acute COVID-19, were predictors of symptom alleviation (p<0·0036). INTERPRETATION: Treatment with SIM01 alleviates multiple symptoms of PACS. Our findings have implications on the management of PACS through gut microbiome modulation. Further studies are warranted to explore the beneficial effects of SIM01 in other chronic or post-infection conditions. FUNDING: Health and Medical Research Fund of Hong Kong, Hui Hoy and Chow Sin Lan Charity Fund, and InnoHK of the HKSAR Government. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.