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.

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.

Detection of Suicidal Ideation in Clinical Interviews for Depression Using Natural Language Processing and Machine Learning: Cross-Sectional Study.

Background: Assessing patients' suicide risk is challenging, especially among those who deny suicidal ideation. Primary care providers have poor agreement in screening suicide risk. Patients' speech may provide more objective, language-based clues about their underlying suicidal ideation. Text analysis to detect suicide risk in depression is lacking in the literature. Objective: This study aimed to determine whether suicidal ideation can be detected via language features in clinical interviews for depression using natural language processing (NLP) and machine learning (ML). Methods: This cross-sectional study recruited 305 participants between October 2020 and May 2022 (mean age 53.0, SD 11.77 years; female: n=176, 57%), of which 197 had lifetime depression and 108 were healthy. This study was part of ongoing research on characterizing depression with a case-control design. In this study, 236 participants were nonsuicidal, while 56 and 13 had low and high suicide risks, respectively. The structured interview guide for the Hamilton Depression Rating Scale (HAMD) was adopted to assess suicide risk and depression severity. Suicide risk was clinician rated based on a suicide-related question (H11). The interviews were transcribed and the words in participants' verbal responses were translated into psychologically meaningful categories using Linguistic Inquiry and Word Count (LIWC). Results: Ordinal logistic regression revealed significant suicide-related language features in participants' responses to the HAMD questions. Increased use of anger words when talking about work and activities posed the highest suicide risk (odds ratio [OR] 2.91, 95% CI 1.22-8.55; P=.02). Random forest models demonstrated that text analysis of the direct responses to H11 was effective in identifying individuals with high suicide risk (AUC 0.76-0.89; P<.001) and detecting suicide risk in general, including both low and high suicide risk (AUC 0.83-0.92; P<.001). More importantly, suicide risk can be detected with satisfactory performance even without patients' disclosure of suicidal ideation. Based on the response to the question on hypochondriasis, ML models were trained to identify individuals with high suicide risk (AUC 0.76; P<.001). Conclusions: This study examined the perspective of using NLP and ML to analyze the texts from clinical interviews for suicidality detection, which has the potential to provide more accurate and specific markers for suicidal ideation detection. The findings may pave the way for developing high-performance assessment of suicide risk for automated detection, including online chatbot-based interviews for universal screening.

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.

Gut microbiome dysbiosis across early Parkinson's disease, REM sleep behavior disorder and their first-degree relatives.

The microbiota-gut-brain axis has been suggested to play an important role in Parkinson's disease (PD). Here we performed a cross-sectional study to profile gut microbiota across early PD, REM sleep behavior disorder (RBD), first-degree relatives of RBD (RBD-FDR), and healthy controls, which could reflect the gut-brain staging model of PD. We show gut microbiota compositions are significantly altered in early PD and RBD compared with control and RBD-FDR. Depletion of butyrate-producing bacteria and enrichment of pro-inflammatory Collinsella have already emerged in RBD and RBD-FDR after controlling potential confounders including antidepressants, osmotic laxatives, and bowel movement frequency. Random forest modelling identifies 12 microbial markers that are effective to distinguish RBD from control. These findings suggest that PD-like gut dysbiosis occurs at the prodromal stages of PD when RBD develops and starts to emerge in the younger RBD-FDR subjects. The study will have etiological and diagnostic implications.

A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic.

STUDY OBJECTIVES: The lifestyles change of children and adolescents during the COVID-19 pandemic due to antipandemic measures can affect their sleep health. Existing studies have used convenient samples and focused on the initial months of the pandemic, leaving a knowledge gap on changes in young people's sleep patterns under the "new normal" under COVID-19. METHODS: As part of a territory-wide epidemiological study in Hong Kong, this cross-sectional study recruited primary and secondary school students by stratified random sampling. Sleep parameters were collected using the structured diagnostic interview for sleep patterns and disorders. We investigated the pandemic's effects on sleep parameters by comparing data of participants recruited pre-COVID and those recruited during COVID using multivariate regression, adjusting for age, sex, household income, seasonality, and presence of mental disorders, and the moderators and mediators of the effects. RESULTS: Between September 1, 2019 and June 2, 2021, 791 primary and 442 secondary school students were recruited and analyzed. Primary school and secondary school participants assessed before COVID had a longer sleep latency on school days (95% confidence interval [CI] = 1.0-5.2 minutes, adjusted P-value = .010; and 95% CI= 3.9-13.0 minutes, adjusted P-value = .004, respectively) and nonschool days (95% CI = 1.7-7.2 minutes, adjusted P-value = .005; 95% CI = 3.4-13.7 minutes, adjusted P-value = .014, respectively). Low household income was a moderator for later bedtime (adjusted P-value = .032) and later sleep onset (adjusted P-value = .043) during nonschool days among secondary school students. CONCLUSIONS: Changes associated with COVID have a widespread and enduring effect on the sleep health of school-aged students in Hong Kong. Household income plays a role in adolescent sleep health resilience, and the impact of antiepidemic measures on the health gaps of the youth should be considered. CITATION: Chau SWH, Hussain S, Chan SSM, et al. A comparison of sleep-wake patterns among school-age children and adolescents in Hong Kong before and during the COVID-19 pandemic. J Clin Sleep Med. 2023;19(4):749-757.

Personality profile and its association with conversion to neurodegenerative disorders in idiopathic REM sleep behavior disorder.

Patients with Parkinson's disease (PD) were described less extraverted and more neurotic. It remained unclear whether similar personality traits could be found in idiopathic rapid eye movement sleep behavior disorder (iRBD), a prodromal stage of PD, and could predict phenoconversion to neurodegenerative disorders. We aimed to investigate the personality profile and its association with future neurodegenerative phenoconversion in iRBD patients. One hundred and eighty-five video-polysomnography confirmed iRBD patients and 91 age- and sex-matched controls underwent personality assessment using the NEO five-factor inventory, and 171 iRBD patients were followed up. Our results showed that iRBD was marginally negatively associated with extraverted personality trait (B = -0.28, 95% confidence interval (CI) = -0.55, -0.001). During a median follow-up of 5.9 years, 47 iRBD patients (27.5%) had phenoconversion. More neurotic (adjusted hazard ratio (HR) = 2.0, 95% CI = 1.3, 3.1) and less extraverted personality traits (adjusted HR = 0.53, 95% CI = 0.36, 0.77) were associated with an increased risk of phenoconversion in iRBD patients. Our findings suggest that personality profile may be a potential prodromal marker of iRBD.

Evolution of Prodromal REM Sleep Behavior Disorder to Neurodegeneration: A Retrospective Longitudinal Case-Control Study.

BACKGROUND AND OBJECTIVES: Individuals with a history of recurrent dream-enactment behaviors, but with subthreshold REM sleep without atonia levels for REM sleep behavior disorder (RBD) diagnosis, are currently classified to have prodromal RBD (pRBD). However, the REM sleep-elevated EMG diagnostic cutoff, progression trajectory, and long-term neurodegenerative outcome of pRBD are not well understood. This study aimed to delineate the evolution of REM sleep EMG levels, determine the EMG cutoff score for diagnosing pRBD, and examine the risk for neurodegenerative diseases of pRBD. METHODS: This retrospective longitudinal case-control study recruited patients with pRBD and age-matched, sex-matched, and follow-up duration-matched controls who were free of neurodegenerative disease at baseline in the Sleep Assessment Unit, the Chinese University of Hong Kong from 1997 to 2018. Patients and controls underwent clinical and video-polysomnography (PSG) assessments at baseline and follow-up(s). REM sleep EMG activity level on mentalis and anterior tibialis (AT) muscles on video-PSG at each visit was scored. The diagnosis of neurodegenerative diseases was confirmed by a neurologist. RESULTS: A total of 44 patients (age 67.4 ± 8.2 years, 6 females) and 44 controls were recruited. The combined REM sleep EMG level on mentalis and AT muscles of patients with pRBD significantly increased during 8.2 ± 3.3 years of follow-up (from 19.3% ± 9.7% to 47.3% ± 27.4% with estimated annual increase of 3.9%), yielding 29 patients with pRBD (66%) meeting the full-blown RBD diagnostic criteria. Baseline REM sleep mentalis and AT muscles EMG activity of patients who developed full-blown RBD could favorably differentiate pRBD from controls (6.3% for mentalis "any" and 9.1% for combination of mentalis any and bilateral AT muscles phasic EMG with an area under the curve of 0.88 [0.78-0.98] and 0.97 [0.92-1.00], respectively). Patients with pRBD had a higher risk for neurodegenerative diseases (9 developed Parkinson disease and 3 developed dementia with Lewy bodies) when compared with controls (5 developed Alzheimer disease, adjusted hazard ratio = 2.95, 95% CI = 1.02-8.54). DISCUSSION: pRBD has a predictive progression in both pathophysiology and neurodegenerative outcome. This finding has significant implications to the nosological status of pRBD, the current REM sleep-related EMG diagnostic criteria, spectrum concept of RBD, and future neuroprotective intervention. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that EMG activity during REM sleep predicts the development of pRBD.

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.

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.

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.