A network model of depressive and anxiety symptoms: a statistical evaluation.

BACKGROUND: Although network analysis studies of psychiatric syndromes have increased in recent years, most have emphasized centrality symptoms and robust edges. Broadening the focus to include bridge symptoms within a systematic review could help to elucidate symptoms having the strongest links in network models of psychiatric syndromes. We conducted this systematic review and statistical evaluation of network analyses on depressive and anxiety symptoms to identify the most central symptoms and bridge symptoms, as well as the most robust edge indices of networks. METHODS: A systematic literature search was performed in PubMed, PsycINFO, Web of Science, and EMBASE databases from their inception to May 25, 2022. To determine the most influential symptoms and connections, we analyzed centrality and bridge centrality rankings and aggregated the most robust symptom connections into a summary network. After determining the most central symptoms and bridge symptoms across network models, heterogeneity across studies was examined using linear logistic regression. RESULTS: Thirty-three studies with 78,721 participants were included in this systematic review. Seventeen studies with 23 cross-sectional networks based on the Patient Health Questionnaire (PHQ) and Generalized Anxiety Disorder (GAD-7) assessments of clinical and community samples were examined using centrality scores. Twelve cross-sectional networks based on the PHQ and GAD-7 assessments were examined using bridge centrality scores. We found substantial variability between study samples and network features. 'Sad mood', 'Uncontrollable worry', and 'Worrying too much' were the most central symptoms, while 'Sad mood', 'Restlessness', and 'Motor disturbance' were the most frequent bridge centrality symptoms. In addition, the connection between 'Sleep' and 'Fatigue' was the most frequent edge for the depressive and anxiety symptoms network model. CONCLUSION: Central symptoms, bridge symptoms and robust edges identified in this systematic review can be viewed as potential intervention targets. We also identified gaps in the literature and future directions for network analysis of comorbid depression and anxiety.

Utilizing plasma drug levels and genetic testing to achieve optimal treatment response in a patient with treatment-resistant schizoaffective disorder.

We report the case of a Chinese male with schizoaffective disorder, an active smoker and a nonresponder to clozapine (600 mg daily). Therapeutic clozapine monitoring was analyzed, revealing a low concentration-dose ratio. A pharmacogenetic test showed that the patient had the CYP1A2*1F/*1F genotype, indicating an ultra-rapid clozapine metabolizer. In combination with fluvoxamine, a CYP1A2 enzyme inhibitor, clozapine plasma concentrations approached the reference range and achieved clinical improvement. This case demonstrates how pharmacogenetics can help understand the value of therapeutic drug monitoring to enhance the treatment of refractory schizoaffective disorder.

Exploring the interplay of psychiatric symptoms, antipsychotic medications, side effects, employment status, and quality of life in Chronic Schizophrenia.

BACKGROUND: Many factors contribute to quality of life (QoL) in patients with schizophrenia, yet limited research examined these factors in patients in China. This cross-sectional study explores subjective QoL and its associated factors in patients. METHODS: The QoL was assessed using the Schizophrenia Quality of Life Scale (SQLS). Clinical symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS) and seven factors were extracted. Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder Scale (GAD-7) were used to assess depression and anxiety. Cognitive impairment was assessed using the Ascertain Dementia 8 (AD8). The Treatment Emergent Symptom Scale (TESS) and Rating Scale for Extrapyramidal Side Effects (RSESE) were used to evaluate the side effects of medications. RESULTS: We recruited 270 patients (male:142,52.6%, mean age:41.9 ± 9.4 years). Positive correlations were observed between SQLS and its subdomains with the total score of BPRS, PHQ-9, GAD-7, AD8, TESS, and RSESE (all P < 0.005). Patients who were taking activating second-generation antipsychotics (SGAs) had lower scores on total SQLS, Motivation/ Energy domain of SQLS (SQLS-ME) as well as Symptoms/ Side effects domain of SQLS (SQLS-SS) compared to those taking non-activating SGAs (all P < 0.005). Multiple regression analysis showed that depressive/ anxiety symptoms and cognitive impairment had significant negative effects on QoL (P ≤ 0.001), while activating SGAs had a positive effect (P < 0.005). Blunted affect and unemployment were inversely associated with the motivation/energy domain (P < 0.001). CONCLUSION: Our findings emphasize the important role of depression/anxiety symptoms and cognitive impairment in the QoL of patients with chronic schizophrenia. Activating SGAs and employment may improve the QoL of these individuals. TRIAL REGISTRATION: This protocol was registered at chictr.org.cn (Identifier: ChiCTR2100043537).

Prevalence of work hour alcohol use and associated factors among psychiatrists in China.

BACKGROUND: Since 2012, work-hour alcohol use (WHAU) has been prohibited in China. However, there is a lack of national data on WHAU among healthcare workers, including psychiatrists. METHODS: We collected data from psychiatrists in 41 tertiary psychiatric hospitals using an online questionnaire, which included demographics, work-related factors, WHAU, and the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C). RESULTS: Out of 2911 psychiatrists who completed the survey, 4.29% reported having heard (3.13%) or witnessed (1.17%) WHAU among colleagues, and .51% (95% CI: .26%-.78%) admitted to their own WHAU. Most participants (95.57%) reported awareness of the policy against WHAU. Poisson regression demonstrated the unawareness of WHAU policy (incidence-rate ratios [IRR] 11.08; 95% CI: 3.56-34.52; P < .001), lower income (IRR .87; 95% CI: .79-0.96; P = .008), and higher AUDIT-C scores (IRR 1.48; 95% CI: 1.22-1.80; P < .001) were significantly associated with WHAU occurrences. CONCLUSIONS: The survey indicates that WHAU among psychiatrists is more prevalent than expected, correlating with insufficient awareness of hospital policies. This suggests a need for targeted educational interventions.

COVID-19 and Sleep Problems: A Perspective from Bibliometric Analysis.

OBJECTIVES: The Coronavirus Disease 2019 (COVID-19) pandemic and the containment measures for COVID-19 have affected sleep quality in the population. This study explored sleep-related research from a bibliometric perspective to provide an overview of the research outputs in this field. METHODS: Original and review articles were retrieved from the Web of Science Core Collection (WOSCC) database from December 2019 to 7 Aug 2023. R package "bibliometrix" was used to summarize the number of articles of authors, institutions, and countries; count the citations of the articles, and generate a Three-Fields Plot. VOSviewer software was applied to visualize the collaboration network among authors and institutions, and to conduct a co-occurrence analysis of keywords. RESULTS: A total of 4,499 articles on COVID-19 and sleep, and 25,883 articles on non-COVID-19 and sleep were included. Sleep related articles were mainly published by authors from China, the USA, and Italy. For COVID-19 and sleep research, Huazhong University of Science was the most productive institution. The Psychiatry Research was the most influential journal across the different subject categories of this field. "Mental health", "anxiety", and "depression" were the most common keywords, while "sleep quality" and "quality of life" were the likely topic areas in terms of future research directions. CONCLUSIONS: Our findings provide a comprehensive perspective for researchers to understand the wider landscape of both COVID-19 and non-COVID-19 sleep-related research area.

Income gap between male and female psychiatric nurses in China: A national survey.

AIM: To investigate gender differences in the actual and expected income among psychiatric nurses in China. BACKGROUND: Although studies have shown that male nurses earn more than female nurses in other countries, there are no published data regarding gender income differences among psychiatric nurses in China. METHODS: We conducted a cross-sectional study involving 41 representative psychiatric hospitals in China. Demographic, income, and job-related data were analyzed using the inverse probability of treatment weighting (IPTW) based on the propensity score. FINDINGS: The sample included 9256 psychiatric nurses, and nearly four-fifths (79.3%) were female. Males earned slightly higher average monthly incomes than female nurses, while initial analysis showed no significant overall gender income difference (p > 0.05). Notably, most participants (92.5%) desired an income increase of at least 10%, with over half (56.2%) expressing significant dissatisfaction with their current income. After adjustment using propensity score combined with IPTW, females in the junior and mid-level groups had significantly lower income than their male counterparts (all p < 0.01), despite having different night shift patterns. However, there were no significant gender differences in actual or expected income among senior-level psychiatric nurses (p > 0.05). CONCLUSION: A majority of psychiatric nurses in China express dissatisfaction with their current incomes and expect higher incomes. Male nurses earned significantly more than female nurses in the junior and mid-level professional groups, potentially due to their differences in night shifts. IMPLICATIONS FOR NURSING POLICY AND HEALTH POLICY: Policymakers and hospital administrators should optimize the income structures of nurses and develop targeted policies to address the gender income gap. Improving nurse income has the potential to enhance motivation and satisfaction within the profession.

The association between the adverse event reporting system and burnout and job satisfaction of nurses: Workplace violence as a mediator.

AIMS: This study aims to explore the association between the implementation of the adverse event reporting system (AERS), burnout, and job satisfaction among psychiatric nurses, with a focus on examining the mediating effect of workplace violence from patients. BACKGROUND: Many organizational and personal factors contribute to burnout and job satisfaction experienced by nurses. AERS, serving as a key component of organizational-level quality improvement system, impacts the overall workplace wellness of nurses. METHODS: A national sample of 9,744 psychiatric nurses from 41 psychiatric hospitals across 29 provinces in China participated. Burnout was measured by the Maslach Burnout Inventory. Job satisfaction was measured using the Minnesota Satisfaction Questionnaire. Workplace violence was assessed by nurses' experience of verbal and physical violence. Multilevel linear regression analyses were carried out to examine if AERS impacts burnout and job satisfaction and to identify the mediating role of workplace violence. RESULTS: AERS was positively associated with job satisfaction, but negatively with burnout and workplace violence. Workplace violence exhibited a positive association with burnout and a negative association with job satisfaction. Mediation analyses indicated that the associations between AERS, burnout, and job satisfaction were mediated by workplace violence. CONCLUSIONS: The application of AERS is associated with a reduction in workplace violence in hospitals, which contributes to the diminished burnout and heightened job satisfaction among psychiatric nurses. IMPLICATIONS FOR NURSING PRACTICE AND HEALTH POLICY: The study highlights the importance of organizational efforts and mechanisms in promoting nurses' well-being. It is necessary for hospital management to create a safe workplace through the implementation of AERS.

Medication treatment for alcohol use disorder in special populations.

BACKGROUND AND OBJECTIVES: Alcohol use disorder (AUD) is a significant public health concern, with underutilized effective treatments, particularly in special populations. This article summarizes the current evidence and guidelines for treating AUD in special populations. METHODS: This article is a literature review that synthesizes the latest research on AUD treatment for special populations. We screened 242 articles and included 57 in our final review. RESULTS: There are four food and Drug Administration-approved medications for AUD (MAUD): disulfiram, oral naltrexone, extended-release injectable naltrexone (XR-NTX), and acamprosate. Naltrexone and disulfiram have the potential to cause liver toxicity, and acamprosate should be avoided in patients with severe kidney disease. Psychosocial treatments should be considered first-line for pregnant and nursing patients. Naltrexone is contraindicated in patients on opioids, as it may precipitate acute withdrawal. For patients experiencing homelessness, nonabstinent treatment goals may be more practical, and XR-NTX should be considered to improve adherence. Limited evidence suggests medication can improve AUD treatment outcomes in adolescents and young adults. For patients with poor treatment response despite adequate medication adherence, switching to a different medication and augmentation with psychosocial treatments should be considered. DISCUSSION AND CONCLUSIONS: Understanding the unique considerations for special populations with AUD is crucial, and addressing their special needs may improve their treatment outcomes. SCIENTIFIC SIGNIFICANCE: Our study significantly contributes to the existing literature by summarizing crucial information for the treatment of AUD in special populations, highlighting distinct challenges, and emphasizing tailored approaches to improve overall health and well-being.

Factors Associated With Utilization of Electroconvulsive Therapy During Psychiatric Hospitalization Among Children and Adolescents in China.

PURPOSE: Based on a nationally representative sample in China, we examined the demographic and clinical correlates of utilization of electroconvulsive therapy (ECT) in child and adolescent (C/A) patients younger than 18 years during psychiatric hospitalization. METHODS: As part of a national survey, 41 provincial tertiary psychiatric hospitals in mainland China were selected. Data from 196 C/A patients who were discharged from these psychiatric hospitals from March 19 to 31, 2019, were retrieved and analyzed. RESULTS: (1) The overall rate of ECT among C/A patients during psychiatric hospitalization was 15.6% (n = 30). (2) Between ECT and non-ECT groups, significant differences were found in sex, age, length of stay, Global Assessment of Functioning at admission, treatment outcome, and self-injurious behavior during hospitalization, and the ratio of marked improvement on discharge. (3) Multiple logistic regression analysis revealed that ECT use was independently and positively associated with an older age, male sex, lower Global Assessment of Functioning, and self-injurious behavior during hospitalization. CONCLUSIONS: The frequency of ECT use was relatively frequent in C/A patients during psychiatric hospitalization in our nationally representative sample in China. Developing more specific and operational criteria for the use of ECT for C/A patients is needed to provide guidance for the optimal use of ECT in this patient population.

Psychometric Properties of the Chinese Version of the ElectroConvulsive Therapy Cognitive Assessment: An Electroconvulsive Therapy-Specific Cognitive Screening Tool.

OBJECTIVES: Electroconvulsive therapy (ECT) is an effective somatic treatment, but it may be limited by cognitive adverse effects. The existing cognitive screening instruments often lack specificity to ECT-associated cognitive deficits. The ElectroConvulsive Therapy Cognitive Assessment was developed and validated in a clinical setting, but the reliability and validity of the Chinese version of ElectroConvulsive Therapy Cognitive Assessment (ECCA-C) have not been studied in a large clinical sample. METHODS: The ECCA-C and the Montreal Cognitive Assessment (MoCA) were administered to patients with major depressive disorder (MDD) undergoing ECT at 3 time points: pretreatment (baseline), before the fifth treatment, and 1 week posttreatment. The instruments were also administered to a sample of healthy subjects. RESULTS: Sixty-five patients with MDD and 50 age- and sex-matched healthy controls were recruited in this study. Overall, the patient group had statistically significantly lower MoCA and ECCA-C scores than the control group (both P values <0.001). The Cronbach α of the ECCA-C was 0.88 at baseline. Statistically significant decreases over time were observed in ECCA-C: pre-ECT (23.9 ± 4.0) > mid-ECT (21.3 ± 3.4) > post-ECT (18.7 ± 4.8) (all P values <0.001), whereas no statistically significant changes in MoCA scores were found at these 3 time points (F = 1.86, P = 0.165). A cutoff score of 26.5 on the ECCA-C was found to best differentiate between MDD patients and healthy controls. CONCLUSIONS: The ECCA-C showed satisfactory psychometric properties and may be a more sensitive instrument than the MoCA to assess cognitive impairment associated with ECT.

Cutting Edge: IL-6-Driven Immune Dysregulation Is Strictly Dependent on IL-6R α-Chain Expression.

IL-6 binds to the IL-6R α-chain (IL-6Rα) and signals via the signal transducer gp130. Recently, IL-6 was found to also bind to the cell surface glycoprotein CD5, which would then engage gp130 in the absence of IL-6Rα. However, the biological relevance of this alternative pathway is under debate. In this study, we developed a mouse model, in which murine IL-6 is overexpressed in a CD11c-Cre-dependent manner. Transgenic mice developed a lethal immune dysregulation syndrome with increased numbers of Ly-6G+ neutrophils and Ly-6Chi monocytes/macrophages. IL-6 overexpression promoted activation of CD4+ T cells while suppressing CD5+ B-1a cell development. However, additional ablation of IL-6Rα protected IL-6-overexpressing mice from IL-6-triggered inflammation and fully phenocopied IL-6Rα-deficient mice without IL-6 overexpression. Mechanistically, IL-6Rα deficiency completely prevented downstream activation of STAT3 in response to IL-6. Altogether, our data clarify that IL-6Rα is the only biologically relevant receptor for IL-6 in mice.

The effects of childhood trauma on personality in unaffected first-degree relatives of patients with major depressive disorder.

ABSTRAC: OBJECTIVES: This study aimed to preliminarily and exploratorily examine the associations between childhood trauma (CT), its subtypes, and personality traits among unaffected first-degree relatives (FDR, children, or siblings) of patients with major depressive disorder (MDD). METHODS: The study sample included three subgroups: MDD patients (N = 85), Patients' FDRs (N = 35), and healthy control individuals (HC, N = 89). The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma and the Eysenck Personality Questionnaire was used to assess personality traits. RESULTS: Significant differences were found in a few personality traits (p < 0.05 for extraversion, neuroticism, and psychoticism) among MDD patients, FDR, and HC, and there were no significant differences between HC and FDR. In the FDR group, compared with those without CT, participants with CT scored significantly higher for neuroticism (N) (F = 3.246, p = 0.046). CT was significantly associated with N, psychoticism (P) and Lie (L), and the strongest association was between CT total score and N. Significantly positive correlations were found between N and sexual abuse (SA) (r = 0.344, p = 0.043), emotional neglect (EN) (r = 0.394, p = 0.019), physical neglect (PN) (r = 0.393, p = 0.019), and CTQ total score (r = 0.452, p = 0.006); between P and CTQ total score (r = 0.336, p = 0.049); and significant negative correlations were found between L and EN (r = -0.446, p = 0.007), CTQ total score (r = -0.375, p = 0.027). CONCLUSION: In unaffected FDRs, there were significant associations between childhood trauma and a few personality traits, including neuroticism, psychoticism, and lie, and emotional neglect was significantly associated with neuroticism.

An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

Cardiovascular Effects of High-Frequency Magnetic Seizure Therapy Compared With Electroconvulsive Therapy.

BACKGROUND: Magnetic seizure therapy (MST) is a novel convulsive therapy that has been shown to have antidepressant efficacy comparable to electroconvulsive therapy (ECT) with fewer cognitive side effects. However, the cardiovascular (CVS) effects of high frequency MST in comparison to ECT have not been investigated. MATERIALS AND METHODS: Forty-five patients with depression received 6 treatment sessions of 100 Hz MST versus 6 bifrontal ECT treatments in a nonrandomized comparative clinical design. Data on CVS function including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and rate pressure product (RPP) were collected at baseline (T0), after the induction of anesthesia but before the electrical stimulation (T1), during convulsion (T2), 2 minutes after cessation of motor seizure (T3), 5 minutes after cessation of motor seizure (T4), and 10 minutes after cessation of motor seizure (T5). Comparisons were made with baseline data and between MST and ECT groups. RESULTS: There were statistically significant elevations in the maximum HR, SBP, DBP, and RPP in patients receiving ECT compared with MST both in the initial and sixth treatments (all P < 0.05). Particularly, at T2, the ECT group had significantly higher HR, SBP, DBP, and RPP than those in MST group both in initial and sixth treatment (all P < 0.001). At the sixth treatment, the ECT group had significantly higher SBP, DBP, and RPP during the treatment than in the MST group (all P < 0.001). LIMITATIONS: The anesthetic choices for this study may limit the generalizability of our findings. The sample size was relatively small. CONCLUSIONS: Compared with ECT, high-frequency MST has fewer CVS side effects and may be a safer option for depression patients with CVS disorders.

Burnout and job satisfaction of psychiatrists in China: a nationwide survey.

BACKGROUND: Despite a significant shortage of psychiatrists in China, an ever-increasing number of psychiatrists in China are experiencing burnout and job dissatisfaction and considering leaving their jobs. Yet, to our knowledge, there have been no nationwide studies to date that examined both burnout and job dissatisfaction of psychiatrists in China. Therefore, this study evaluated burnout and job dissatisfaction of psychiatrists in China, and identified relevant characteristics. METHODS: We conducted a nationwide, cross-sectional survey in March 2019. Psychiatrists from all tertiary psychiatric hospitals in China were invited to participate. The Maslach Burnout Inventory-Human Service Survey and the short version of the Minnesota Satisfaction Questionnaire were used to measure burnout and job satisfaction. Data on socio-demographic and occupational characteristics were collected. Multivariate logistic regression was conducted to identify socio-demographic and occupational characteristics associated with burnout and job satisfaction. RESULTS: In total, 4520 psychiatrists from tertiary psychiatric hospitals in China completed the questionnaire. Overall, 38.4% of respondents met the criteria for burnout and 35.6% were dissatisfied with their jobs. Being male, more years of practice, having no leadership role, and longer working hours per week were significantly associated with burnout and job dissatisfaction. Lower monthly pay was significantly associated with job dissatisfaction but not burnout. Moreover, burnout was significantly associated with job dissatisfaction. CONCLUSIONS: Our data suggest a high rate of burnout and job dissatisfaction among psychiatrists in China. In order to preserve and strengthen the mental health workforce, proactive measures are urgently needed to mitigate burnout and job dissatisfaction among psychiatrists in China.

A sequence analysis of hospitalization patterns and service utilization in patients with major psychiatric disorders in China.

BACKGROUND: Understanding the long-term inpatient service cost and utilization of psychiatric patients may provide insight into service demand for these patients and guide the design of targeted mental health programs. This study assesses 3-year hospitalization patterns and quantifies service utilization intensity of psychiatric patients in Beijing, China. METHODS: We identified patients admitted for one of three major psychiatric disorders (schizophrenia, bipolar and depressive disorders) between January 1 and December 31, 2013 in Beijing, China. Inpatient admissions during the following 3 years were extracted and analyzed using sequence analysis. Clinical characteristics, psychiatric and non-psychiatric service use of included patients were analyzed. RESULTS: The study included 3443 patients (7657 hospitalizations). The patient hospitalization sequences were grouped into 4 clusters: short stay (N = 2741 (79.61% of patients), who had 126,911 or 26.82% of the hospital days within the sample), repeated long stay (N = 404 (11.73%), 76,915 (16.26%) days), long-term stay (N = 101 (2.93%), 59,909 (12.66%) days) and permanent stay (N = 197 (5.72%), 209,402 (44.26%) days). Length and frequency of hospitalization, as well as readmission rates were significantly different across the 4 clusters. Over the 3-year period, hospitalization days per year decreased for patients in the short stay and repeated long stay clusters. Patients with schizophrenia (1705 (49.52%)) had 78.4% of cumulative psychiatric stays, with 11.14% of them in the permanent stay cluster. Among patients with depression, 23.11% had non-psychiatric hospitalizations, and on average 46.65% of their total inpatient expenses were for non-psychiatric care, the highest among three diagnostic groups. CONCLUSION: Hospitalization patterns varied significantly among psychiatric patients and across diagnostic categories. The high psychiatric care service use of the long-term and permanent stay patients underlines the need for evidence-based interventions to reduce cost and improve care quality.

Off-label use of antipsychotic medications in psychiatric inpatients in China: a national real-world survey.

BACKGROUND: The off-label use of antipsychotic medications is common in many countries, and the extent of such use in psychiatric inpatients in China has not been sufficiently studied. The purpose of this study was to survey the incidence and examine the correlates of off-label antipsychotic use in a large, nationally-representative sample in China. METHODS: This study included discharged psychiatric patients between March 19 and 31, 2019 from 41 tertiary psychiatric hospitals across 29 provinces in China. Their socio-demographic and clinical data were collected and analyzed. RESULTS: After excluding patients with schizophrenia spectrum disorder or bipolar disorder, 981 patients were included in the analysis. Overall, antipsychotics were prescribed to 63.2% (95%CI 60.2-66.2%) of the sample. Antipsychotics were used in a wide spectrum of psychiatric disorders, with the rate being the highest among patients with dissociative (conversion) disorders (89.9, 95%CI 83.0-94.8%), organic mental disorders (81.7, 95%CI 73.1-88.7%), dementia (79.0,95%CI 67.8-87.9%), obsessive-compulsive disorder (77.8, 95%CI 55.7-92.5%), mental disorders due to psychoactive substances (75.3,95%CI 64.7-84.2%), behavioural and emotional disorders with onset usually occurring in childhood and adolescence (71.4, 95%CI 45.5-90.1%), somatoform disorders (63.2, 95%CI 40.8%-82..2%), major depression disorder (53.7,95%CI 48.8-58.6%), anxiety disorder (38.8,95%CI 30.5-47.7%), and insomnia (25.0, 95%CI 8.5-28.9%). The top three most commonly used antipsychotics were olanzapine (29.1%), quetiapine (20.3%) and risperidone (6.8%), and their corresponding average doses were 9.04 ± 5.80 mg/day, 185.13 ± 174.72 mg/day, and 2.98 ± 1.71 mg/day, respectively. A binary logistic regression showed that younger age, having the Employee Health Insurance or Residents Health Insurance, having psychotic symptoms and requiring restraint during hospitalization were significantly associated with off-label use of antipsychotics. CONCLUSION: Off-label use of antipsychotics is very common in psychiatric inpatients in China, mainly with moderate-dose use of single agents. However, the efficacy and safety of this practice is uncertain for many diagnoses and for the elderly. Clinicians should be cautious about this practice while waiting for more research data.

Alcohol Use Among Mental Health Professionals in China: A Nationwide Cross-sectional Survey.

AIM: To survey the use of alcohol, and its correlates by mental health professions in China, a nation where there is rapid increase in alcohol consumption and problems. METHODS: As a part of a large-scale, nation-wide online survey of healthcare professionals, we collected demographic variables and other health-related variables anonymously. The Alcohol Use Disorder Identification Test-Concise (AUDIT-C) was used to collect data on alcohol use. RESULTS: 13,980 mental health professionals completed the survey (4382 doctors, 9339 nurses and 259 clinical psychologists), representing 64% of the total targeted. Respondents were predominantly female (75.1%). Alcohol consumption was reported by 41.8% of participants (by 53.9% of doctors, 36.2% of nurses and 40.5% of clinical psychologists). Based on the cut-off scores of the AUDIT-C (≥3 for women and ≥4 for men), 7.5% were classified as probable alcohol misusers in the past year, and the rates were 10.2% in doctors, 6.3% in nurses and 5.8% in clinical psychologists. Multiple logistic regression showed that male sex (OR = 3.772; CI = 3.206-4.439), being a doctor (OR = 1.259; CI = 1.052-1.506), being divorced or widowed (OR = 1.979; CI = 1.467-2.666), having an associate degree or less (OR = 1.809; CI = 1.040-3.147), working in Northeast China (OR = 1.538; CI = 1.281-1.848) and the habit of smoking (OR = 3.345; CI = 2.280-3.967) were significantly associated with alcohol misuse. CONCLUSIONS: Alcohol use and misuse were relatively common among mental health professionals in China, and male sex, being a doctor, with lower education, working in Northeast China and cigarette smoking were significant associations. Awareness and interventions are recommended to promote healthier use of alcohol in this professional group, especially among risk subgroups.

Elevated Rates of Restraint and Seclusion in Child and Adolescent Psychiatric Inpatients in China and Their Associated Factors.

To investigate the rate of restraint and seclusion (R&S) use in child and adolescent psychiatric inpatients in China and to examine factors associated with use of these interventions. As part of an official national survey, 41 provincial tertiary psychiatric hospitals in China were selected. Data from 196 youth inpatients discharged from these hospitals from March 19 to 31, 2019 were retrieved and analyzed. (1) The overall rate of R&S was 29.1% (N = 57) and the rate of restraint was 28.6% (N = 56), and seclusion was 11.7% (N = 23) respectively. (2) Compared to patients who did not require R&S, those who required R&S were more likely to have been hospitalized on an involuntary basis, more likely to present with either manic symptoms or aggressive behavior as primary reason for admission, had more frequent aggressive behaviors during hospitalization, and had a significantly longer length of stay. (3) A logistic regression showed that aggressive behaviors during hospitalization was significantly associated with the use of R&S (OR = 21.277, p < 0.001), along with three other factors: manic symptoms as a reason for admission, involuntary admission and a lower GAF score at admission (all p < 0.01). The rate of R&S is dramatically higher in child and adolescent psychiatric hospitalizations in China compared to other regions. Targeted training of staff, development of precise operational guidelines for appropriate use of R&S, and strict oversight are urgently needed to minimize the inappropriate use of R&S in child and adolescent patients.

Alternative Splice Forms of CYLD Mediate Ubiquitination of SMAD7 to Prevent TGFB Signaling and Promote Colitis.

BACKGROUND & AIMS: The CYLD lysine 63 deubiquitinase gene (CYLD) encodes tumor suppressor protein that is mutated in familial cylindromatosus, and variants have been associated with Crohn disease (CD). Splice forms of CYLD that lack exons 7 and 8 regulate transcription factors and functions of immune cells. We examined the expression of splice forms of CYLD in colon tissues from patients with CD and their effects in mice. METHODS: We performed immunohistochemical analyses of colon tissues from patients with untreated CD and patients without inflammatory bowel diseases (controls). We obtained mice that expressed splice forms of CYLD (sCYLD mice) without or with SMAD7 (sCYLD/SMAD7 mice) from transgenes and CYLD-knockout mice (with or without transgenic expression of SMAD7) and performed endoscopic analyses. Colitis was induced in Rag1-/- mice by transfer of CD4+ CD62L+ T cells from C57/Bl6 or transgenic mice. T cells were isolated from mice and analyzed by flow cytometry and quantitative real-time polymerase chain reaction and intestinal tissues were analyzed by histology and immunohistochemistry. CYLD forms were expressed in mouse embryonic fibroblasts, primary T cells, and HEK293T cells, which were analyzed by immunoblot, mobility shift, and immunoprecipitation assays. RESULTS: The colonic lamina propria from patients with CD was infiltrated by T cells and had higher levels of sCYLD (but not full-length CYLD) and SMAD7 than tissues from controls. Incubation of mouse embryonic fibroblasts and T cells with transforming growth factor ß increased their production of sCYLD and decreased full-length CYLD. Transgenic expression of sCYLD and SMAD7 in T cells prevented the differentiation of regulatory T cells and T-helper type 17 cells and increased the differentiation of T-helper type 1 cells. The same effects were observed in colon tissues from sCYLD/SMAD7 mice but not in those from CYLD-knockout SMAD7 mice. The sCYLD mice had significant increases in the numbers of T-helper type 1 cells and CD44high CD62Llow memory-effector CD4+ T cells in the spleen and mesenteric lymph nodes compared with wild-type mice; sCYLD/SMAD7 mice had even larger increases. The sCYLD/SMAD7 mice spontaneously developed severe colitis, with infiltration of the colon by dendritic cells, neutrophils, macrophages, and CD4+ T cells and increased levels of Ifng, Il6, Il12a, Il23a, and Tnf mRNAs. Co-transfer of regulatory T cells from wild-type, but not from sCYLD/SMAD7, mice prevented the induction of colitis in Rag1-/- mice by CD4+ T cells. We found increased levels of poly-ubiquitinated SMAD7 in sCYLD CD4+ T cells. CYLD formed a nuclear complex with SMAD3, whereas sCYLD recruited SMAD7 to the nucleus, which inhibited the expression of genes regulated by SMAD3 and SMAD4. We found that sCYLD mediated lysine 63-linked ubiquitination of SMAD7. The sCYLD-SMAD7 complex inhibited transforming growth factor ß signaling in CD4+ T cells. CONCLUSIONS: Levels of the spliced form of CYLD are increased in colon tissues from patients with CD. sCYLD mediates ubiquitination and nuclear translocation of SMAD7 and thereby decreases transforming growth factor ß signaling in T cells. This prevents immune regulatory mechanisms and leads to colitis in mice.