Scalable mixed model methods for set-based association studies on large-scale categorical data analysis and its application to exome-sequencing data in UK Biobank.

The ongoing release of large-scale sequencing data in the UK Biobank allows for the identification of associations between rare variants and complex traits. SAIGE-GENE+ is a valid approach to conducting set-based association tests for quantitative and binary traits. However, for ordinal categorical phenotypes, applying SAIGE-GENE+ with treating the trait as quantitative or binarizing the trait can cause inflated type I error rates or power loss. In this study, we propose a scalable and accurate method for rare-variant association tests, POLMM-GENE, in which we used a proportional odds logistic mixed model to characterize ordinal categorical phenotypes while adjusting for sample relatedness. POLMM-GENE fully utilizes the categorical nature of phenotypes and thus can well control type I error rates while remaining powerful. In the analyses of UK Biobank 450k whole-exome-sequencing data for five ordinal categorical traits, POLMM-GENE identified 54 gene-phenotype associations.

Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation.

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to diabetes and coronary heart disease. To expand the unclear genetic mechanism underlying AIWG, we conducted a two-stage genome-wide association study in Han Chinese patients with schizophrenia. The study included a discovery cohort of 1936 patients and a validation cohort of 534 patients, with an additional 630 multi-ancestry patients from the CATIE study for external validation. We applied Mendelian randomization (MR) analysis to investigate the relationship between AIWG and antipsychotic-induced lipid changes. Our results identified two novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P = 1.373 × 10-9) and rs3824417 in PTPRD (P = 3.348 × 10-9) in Chinese Han samples. The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. Colocalization analysis suggested that AIWG and type 2 diabetes (T2D) shared a causal variant in PEPD. Polygenic risk scores (PRSs) for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P = 7.58 × 10-4) and triglycerides (P = 2.06 × 10-3) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating antipsychotic-induced lipid changes, PRSs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC = 0.79, R2 = 0.332). Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia.

Interactive effect of air pollution and genetic risk of depression on processing speed by resting-state functional connectivity of occipitoparietal network.

BACKGROUND: Air pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function. METHODS: Eligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months' ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 µm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility. RESULTS: Using a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed. CONCLUSIONS: Our cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.

Sleep-specific repetitive negative thinking processes and prenatal insomnia symptoms: A naturalistic follow-up study from mid- to late-pregnancy.

Insomnia symptoms are highly prevalent during pregnancy; therefore, identifying modifiable risk markers is important for risk prediction and early intervention. This study aimed to examine the role of sleep-specific rumination and sleep-specific worry in prenatal insomnia symptoms. A total of 859 married pregnant women without history of psychiatric illnesses (mean [standard deviation] age, 30.15 [3.86] years; 593 [69.0%] with a bachelor's degree or above) were enrolled from the obstetrical outpatient departments of two tertiary comprehensive hospitals in Shandong, China, who completed assessments of sleep-specific rumination, sleep-specific worry, and insomnia symptoms at baseline (mid-pregnancy) and follow-up (late-pregnancy). Measures included Daytime Insomnia Symptom Response Scale, Anxiety and Preoccupation about Sleep Questionnaire, and Insomnia Severity Index. Our results showed that after controlling for covariates, both sleep-specific rumination and sleep-specific worry showed significant concurrent and prospective associations with insomnia symptoms, and the increases in scores of sleep-specific rumination and sleep-specific worry over time were significantly associated with the increased likelihood of insomnia symptoms at follow-up. Moreover, the increases in sleep-specific rumination and sleep-specific worry over time were significantly associated with the increased likelihood of reporting newly developed insomnia symptoms rather than persistent normal sleep. However, the changes in sleep-specific rumination and sleep-specific worry were not significantly associated with the likelihood of reporting persistent or remitted insomnia symptoms rather than persistent normal sleep. In conclusion, sleep-specific rumination and sleep-specific worry were significantly associated with concurrent or subsequent insomnia symptoms; thus, they may be promising cognitive risk markers and intervention targets.

Association between transition patterns of sleep problems and suicidal ideation in Chinese female nurses: A prospective study.

OBJECTIVE: Suicidal ideation and sleep problems are both common in nurses. However, few longitudinal studies are available to examine the temporal association between sleep and suicidal ideation in nurses. METHOD: Data from the Health Longitudinal Survey of Nurses in Shandong Province was analyzed, involving 623 female nurses who had completed data of concern in 2018 (T1) and 2019 (T2). Sleep problem was assessed by the Pittsburgh Sleep Quality Index, in which the transition patterns for global and specific sleep component and the cumulative number of sleep component problems were defined. Suicidal ideation was measured by the ninth item of the Patient Health Questionnaire. Binary logistic regression was used to explore the association between sleep and suicidal ideation. RESULTS: Chronic and deteriorated global sleep problems is associated with a greater risk of suicidal ideation. For the specific component of sleep, sleep disturbance and short sleep duration are associated with a higher risk of suicidal ideation. The higher number of cumulative sleep component problems is associated with a higher risk of suicidal ideation. CONCLUSION: Findings indicate sleep disturbance and short sleep duration may be pathways to suicidal ideation. Initiatives that target at sleep problems may be important to reduce suicidal ideation in nurses.

Psychometric properties of the Chinese version of the Cognitive Reserve Assessment Scale in Health in patients with cancer.

BACKGROUND: Cognitive reserve is a modifiable factor that could prevent cognitive decline in patients with cancer. The Cognitive Reserve Assessment Scale in Health (CRASH) is an instrument used to assess cognitive reserve. This study aims to develop and examine the psychometric properties of the Chinese version of the CRASH for patients with cancer. METHODS: A cross-sectional survey was conducted with 167 cancer patients from four wards of two hospitals in China. Thirty-one patients were re-assessed to examine the test-retest reliability. Four translators and three reviewers developed the Chinese version of the scale. We assessed its structural validity, concurrent validity, internal consistency, test-retest reliability, measurement error, and floor/ceiling effects. RESULTS: Confirmatory factor analysis showed a good model fit with the four-factor structure of the original CRASH. The CRASH scores were statistically significantly associated with neuropsychological test scores, indicating sufficient concurrent validity. The internal consistency was acceptable, except for leisure activities, with standardized Cronbach's alphas (0.64-0.94) and standardized Omega (0.66-0.95). There was excellent test-retest reliability, with a high intraclass correlation coefficient (0.914-0.993) of total scores and scores for each domain. The measurement error was acceptable, and no floor or ceiling effects were observed. CONCLUSIONS: The Chinese version of the CRASH is a valid and reliable instrument to assess cognitive reserve in patients with cancer. Moreover, cognitive reserve measured by the CRASH was associated with low cognitive performance in cancer patients.

Therapeutic outcomes wide association scan of different antipsychotics in patients with schizophrenia: Randomized clinical trials and multi-ancestry validation.

AIM: This study identified discrepant therapeutic outcomes of antipsychotics. METHODS: A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables. RESULTS: In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (ß = -2.17); ziprasidone related to higher risk of increased QT interval (ß range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort. CONCLUSION: Future precision medicine should focus on personalized side-effects.

Role of the EM clustering method in determining the geochemical background of As and Cr in soils: a case study in the north of Changchun, China.

Determining the geochemical background for heavy metals is vital in soil management activities. Although many statistical methods for geochemical background determination have been proposed, the multi-population problem of geochemical data, primarily regional ones, derived mainly from mixing multiple populations belonging to various geological sources or processes, needs to be better addressed. In this study, the Expectation-Maximization (EM) algorithm was employed to separate multiple populations in a 1:250,000 scale regional geochemical data set of soils in a lithologically complex region in the north of Changchun, China. The data set included 3746 surface soil samples analyzed for SiO2, K2O, Al2O3, CaO, La, Rb, Y, Ti, Ce, V, Cr, and As. The potential high-risk areas of As and Cr were determined before and after the separation of multiple populations. The comparison results show that the EM clustering method can efficiently separate multiple populations and determine soil geochemical background more reasonably, thus eliminating false contamination that is easily misidentified and better revealing concealed contamination that is challenging to detect.

Prenatal stress self-help mindfulness intervention via social media: a randomized controlled trial.

BACKGROUND: Prenatal stress is a pressing issue. However, there is a lack of robust evidence for psychosocial interventions to manage this problem. AIMS: This study aimed to examine the effectiveness of a mindfulness-based intervention on reducing prenatal stress compared to participation in health education groups. METHODS: A randomized controlled trial was conducted in a prenatal clinic of comprehensive tertiary care from April to October 2017. A total of 108 pregnant women were randomly assigned to an intervention or a control group. Participants completed self-report measures of depression, anxiety, perceived stress, fatigue, positive and negative affect, and mindfulness before, immediately after, and 15 weeks after the 4-week intervention period. Generalized estimating equations were used to analyze the intervention outcomes. RESULTS: The results supported greater improvement in terms of perceived stress (Wald χ2=26.94, p<0.001), fatigue (Wald χ2=17.61, p<0.001), positive affect (Wald χ2=9.03, p = 0.011), negative affect (Wald χ2=11.37, p = 0.003), and mindfulness (Wald χ2=24.97, p<0.001) in the intervention group than in the control group. CONCLUSIONS: The self-help mindfulness intervention decreased prenatal stress and negative affect and improved positive affect and mindfulness.

Prenatal Symptom Cluster of Psychopathology and Associations With Mindfulness and Rumination: A Network Analysis.

ABSTRACT: The present study aimed to examine the interrelationships of prenatal psychopathology (specifically symptom cluster), dispositional mindfulness, and rumination using network analysis. Network analysis estimates the links between symptoms and can evaluate the presence and strength of the links. A total of 1122 pregnant women were recruited from a tertiary hospital in China. Psychopathology symptoms (including anxiety, depression, stress, fatigue, sleep, fear of childbirth [FOC], and memory problems) were assessed and used along with mindfulness and rumination to construct networks of association using R. Results illustrated five communities within the network. Anxiety resulted in the highest strength of centrality followed by two symptoms: FOC and retrospective memory. Paths showed that mindfulness was directly connected to depression, prospective memory, retrospective memory, and lack of positive anticipation in FOC, whereas mindfulness was connected indirectly through rumination to anxiety, fatigue, stress, and sleep problems. The findings reinforce that anxiety is a key symptom of prenatal psychopathology and requires priority consideration. The direct associations between mindfulness and prenatal psychopathology symptoms provide potential targets for future mindfulness-based interventions, and mindfulness reducing rumination thus in turn decrease anxiety, suggesting potential mediating mechanism of mindfulness.

Asthma Promotes Choroidal Neovascularization via the Transforming Growth Factor Beta1/Smad Signalling Pathway in a Mouse Model.

INTRODUCTION: The association between age-related macular degeneration and asthma is controversial. Transforming growth factor beta (TGF-ß), which plays a critical role in asthma, has been extensively studied with regard to its function in choroidal neovascularization (CNV). In the present study, we aimed to investigate the role of TGF-ß and the possible mechanism of CNV formation complicated with asthma and to explore the effect of a TGF-ß inhibitor on CNV development in asthma mouse models. METHODS: Laser-induced CNV and ovalbumin-induced asthma mouse models were divided into 5 groups: control group, acute asthma group, chronic asthma group, inhibitor-treated acute asthma group, and inhibitor-treated chronic asthma group. The gene expression patterns of angiogenic cytokines, vascular endothelial growth factor (VEGF) receptors and inflammasomes in the control group, acute asthma group, and chronic asthma group were detected using a QuantiGene Plex 6.0 Reagent System. Fundus fluorescein angiography and histology of CNV lesions stained with haematoxylin-eosin were performed to evaluate CNV formation. Quantitative real-time PCR and western blotting were used to assess TGF-ß1, TGF-ß2, and VEGF expression and Smad2/3, AKT, p38 MAPK, and ERK1/2 signal transduction and phosphorylation in retinal and choroidal tissues from each group. RESULTS: In this study, we verified that laser treatment led to more CNV and vascular leakage in asthmatic mice than that in control mice. The changes were particularly notable in the chronic asthma group. The respective TGF-ß1, VEGF, and phosphorylated Smad2/3 (p-Smad2/3) mRNA and protein levels in retinal and choroidal tissues were significantly upregulated in both the acute and chronic asthma groups. After injection of a TGF-ß inhibitor, a distinct decline in VEGF, TGF-ß1, and p-Smad2/3 protein and mRNA levels was observed, and the mean CNV area also decreased. CONCLUSION: We provide new evidence that asthma could be a risk factor for CNV development via the TGF-ß1/Smad signalling pathway. A TGF-ß inhibitor can be applied as a useful, adjunctive therapeutic strategy for preventing CNV formation in asthmatic patients.

Work-related potential traumatic events and job burnout among operating room nurses: Independent effect, cumulative risk, and latent class approaches.

AIMS: The objective of this study is to explore and compare the strength of associations between work-related potential traumatic events and burnout among operating room nurses based on three different approaches. DESIGN: The study followed a multisite cross-sectional design. METHODS: A stratified sampling method was conducted. Cities in the Shandong Province were divided into four groups, and two tertiary hospitals were randomly selected from all tertiary hospitals in cities of each group. A total of 361 eligible operating room nurses provided valid questionnaires between June and November 2019. Work-related potential traumatic events questionnaire and the Chinese version of the Maslach Burnout Inventory were conducted. Associations between individual, cumulative potential traumatic events, as well as latent class analysis-derived patterns of potential traumatic experiences with burnout were examined using logistic regression analysis. RESULTS: Specific traumatic events (e.g., patients' sudden death, bullying and ostracism from colleagues) were independently associated with an increased risk of burnout. Work-related potential traumatic events had a cumulative effect on burnout, whereby operating room nurses exposed to cumulative potential traumatic events carried a higher risk for burnout than others. The "multiple work-related potential traumatic events" pattern derived by latent class analysis was related to an increased risk of high depersonalization. CONCLUSION: Operating room nurses who reported specific or multiple work-related potential traumatic events were at high risk for burnout. It is of great significance to provide qualified and timely counselling or support. IMPACT: This study is the first to focus on work-related potential traumatic events among operating room nurses and examine their relationship with burnout based on three perspectives. The findings could help identify those operating room nurses who are at high risk of burnout in clinical practice. Hospital managers should develop targeted interventions to prevent or mitigate the harmful impact of potential traumatic events on occupational health.

The association of different parenting styles among depressed parents and their offspring's depression and anxiety: a cross-sectional study.

BACKGROUND: Parenting styles play a critical role in children's development, especially for those in families with a depressed parent. To date, no study has explored whether youth perceptions of parenting style are heterogeneous in families with a depressed parent or whether heterogeneous parenting styles are associated with children's internalizing symptoms. METHODS: Participants were children aged 8-16 years who had a parent with major depressive disorder; they were enrolled through their parents, who were outpatients at two hospitals in Ningxia. Parenting styles were measured using the Parental Bonding Instrument. Youth depression and anxiety were measured using the Depression Self-Rating Scale for Children and the Screen for Child Anxiety-Related Emotional Disorders, respectively. We applied latent profile analysis to identify the subtypes of parenting styles with similar patterns. Differences between subtypes in relation to demographic variables and parenting style scores were calculated using one-way ANOVAs, Wilcoxon rank sum tests, and chi-squared tests. Bivariate logistic analyses were conducted to examine the associations between parental bonding subtypes and children's depression and anxiety. RESULTS: Four parenting styles were identified through latent profile analysis: care-autonomy, overprotection-indifference, indifference, and undifferentiated parenting. Youth with care-autonomy parents had a lower risk of depression (OR: 0.16; 95% CI: 0.06-0.41) and anxiety (OR: 0.22; 95% CI: 0.10-0.48), while indifference parenting increased children's risk of depression (OR: 5.29; 95% CI: 1.30-21.54) more than undifferentiated parenting. CONCLUSIONS: Children with a depressed parent had heterogeneous perceptions of parenting styles. Mothers' and fathers' parenting styles were largely congruent. Care-autonomy parenting (high care and high autonomy) may decrease children's risk of depression, whereas indifference parenting (low care and autonomy) may increase their risk of depression.

Association analysis between the interaction of RAS family genes mutations and papillary thyroid carcinoma in the Han Chinese population.

Papillary thyroid carcinoma (PTC) is the major subtype of thyroid cancer, accounting for 75%-85% of all thyroid malignancies. This study aimed to identify the association between the interactions of single nucleotide polymorphisms (SNPs) in RAS family genes and PTC in the Han Chinese population, to provide clues to the pathogenesis and potential therapeutic targets for PTC. Hap Map and NCBI-db SNP databases were used to retrieve SNPs. Haploview 4.2 software was used to filter SNPs based on specific parameters, six SNPs of RAS gene (KRAS-rs12427141, KRAS-rs712, KRAS-rs7315339, HRAS-rs12628, NRAS-rs14804 and NRAS-rs2273267) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) in 673 PTC patients and 657 healthy controls, the interactive effect was evaluated by crossover analysis, logistic regression and GMDR software. We found that genetic mutation in rs712 have significant associations with PTC risk after Bonferroni correction (p<0.001). The interaction between KRAS-rs12427141 and HRAS-rs12628 increased the risk of PTC (U=-2.119, p<0.05), the interaction between KRAS-rs2273267 and HRAS-rs7315339 reduced the risk of PTC (U=2.195, p<0.05). GMDR analysis showed that the two-factor model (KRAS-rs712, NRAS-rs2273267) was the best (p=0.0107). Summarily, there are PTC-related interactions between RAS family genes polymorphisms in the Han Chinese population.

A Retrospective Study of 268 Patients with SARS-CoV-2 Infection to Evaluate the Association Between Blood Glucose and Severity of COVID-19 Pneumonia and Patient Mortality.

BACKGROUND Diabetes is one of the most commonly reported comorbidities among patients infected with SARS-CoV-2. This retrospective study of patients with SARS-CoV-2 infection was conducted to evaluate the association between blood glucose levels and the severity of COVID-19 pneumonia and patient mortality. MATERIAL AND METHODS A total of 268 patients with confirmed SARS-CoV-2 infection were included in this retrospective study. We obtained demographic characteristics, clinical symptoms, laboratory data, and survival information from patients' electronic medical records. Blood glucose was measured on admission to the hospital. Comorbidities, including hypertension, diabetes, chronic kidney disease, chronic liver disease, chronic obstructive pulmonary disease, and cardiovascular disease, were collected by self-reported medical history. RESULTS Significantly higher risks of severe COVID-19 were found in patients with blood glucose levels ranging from 5.53 to 7.27 mmol/L (odds ratio [OR], 3.98; 95% confidence interval [CI], 1.81-8.75) and in patients with blood glucose ≥7.27 mmol/L (OR, 12.10; 95% CI, 5.53-26.48) than in those with blood glucose <5.53 mmol/L. There was a trend toward better survival in patients with blood glucose <5.53 mmol/L than in patients with blood glucose from 5.53 to 7.27 mmol/L (hazard ratio [HR], 6.34; 95% CI, 1.45-27.71) and ≥7.27 mmol/L (HR, 19.37; 95% CI, 4.68-80.17). Estimated 10-day overall survival rates were 96.8%, 90.6%, and 69.3% in patients with blood glucose <5.53 mmol/L, 5.53 to 7.27 mmol/L, and ³7.27 mmol/L, respectively. CONCLUSIONS Hyperglycemia was association with severity of COVID-19 pneumonia and with increased patient mortality. These findings support the need for blood glucose monitoring and control of hyperglycemia in patients with COVID-19 pneumonia.

Mindfulness improves health worker's occupational burnout: the moderating effects of anxiety and depression.

OBJECTIVE: This study aims to test whether health workers experiencing both depression, anxiety and burnout would show severer burnout symptoms, and the potential moderating effect of anxiety and depression on mindfulness improving burnout. METHODS: This study was conducted in a comprehensive hospital of China in 2016. A total of 924 healthcare professionals were included in this cross-sectional study with a response rate of 82.0%. Maslach Burnout Inventory, Patient Health Questionnaire-9, Generalized Anxiety Disorder, Perceived Stress Scale and Short Inventory of Mindfulness Capability were used to measure burnout, depression, anxiety, perceived stress and mindfulness. Univariate analysis, correlation analysis, mediation analysis and moderated mediation analysis were conducted. RESULTS: Burnout and anxiety group (BA) and burnout and depression group (BD) reported significantly higher burnout scores compared to the burnout-only group (BO) (59.90 ± 15.700, 56.20 ± 13.190, and 49.99 ± 11.955, respectively). Perceived stress was a mediator between mindfulness and occupational burnout, and depression and anxiety significantly moderated the mediation path between mindfulness and occupational burnout (ß for stress in moderated mediation models with depression and anxiety respectively: ß = 1.8088, p < 0.001, and ß = 1.7908, p < 0.001). For participants who experienced a high level of depression, less occupational burnout was reduced as mindfulness increased. Indirect effect of mindfulness reducing occupational burnout was greater among participants who experienced less anxiety. CONCLUSIONS: Depression and anxiety weakened the mindfulness ability on relieving occupational burnout, which could be the potential mechanism of the worsening effect of depression and anxiety.

Effectiveness of Smartphone-Based Mindfulness Training on Maternal Perinatal Depression: Randomized Controlled Trial.

BACKGROUND: Despite potential for benefit, mindfulness remains an emergent area in perinatal mental health care, and evidence of smartphone-based mindfulness training for perinatal depression is especially limited. OBJECTIVE: The objective of this study was to evaluate the effectiveness of a smartphone-based mindfulness training intervention during pregnancy on perinatal depression and other mental health problems with a randomized controlled design. METHODS: Pregnant adult women who were potentially at risk of perinatal depression were recruited from an obstetrics clinic and randomized to a self-guided 8-week smartphone-based mindfulness training during pregnancy group or attention control group. Mental health indicators were surveyed over five time points through the postpartum period by online self-assessment. The assessor who collected the follow-up data was blind to the assignment. The primary outcome was depression as measured by symptoms, and secondary outcomes were anxiety, stress, affect, sleep, fatigue, memory, and fear. RESULTS: A total of 168 participants were randomly allocated to the mindfulness training (n=84) or attention control (n=84) group. The overall dropout rate was 34.5%, and 52.4% of the participants completed the intervention. Mindfulness training participants reported significant improvement of depression (group × time interaction χ24=16.2, P=.003) and secondary outcomes (χ24=13.1, P=.01 for anxiety; χ24=8.4, P=.04 for positive affect) compared to attention control group participants. Medium between-group effect sizes were found on depression and positive affect at postintervention, and on anxiety in late pregnancy (Cohen d=0.47, -0.49, and 0.46, respectively). Mindfulness training participants reported a decreased risk of positive depressive symptom (Edinburgh Postnatal Depression Scale [EPDS] score>9) compared to attention control participants postintervention (odds ratio [OR] 0.391, 95% CI 0.164-0.930) and significantly higher depression symptom remission with different EPDS reduction scores from preintervention to postintervention (OR 3.471-27.986). Parity did not show a significant moderating effect; however, for nulliparous women, mindfulness training participants had significantly improved depression symptoms compared to nulliparous attention control group participants (group × time interaction χ24=18.1, P=.001). CONCLUSIONS: Smartphone-based mindfulness training is an effective intervention in improving maternal perinatal depression for those who are potentially at risk of perinatal depression in early pregnancy. Nulliparous women are a promising subgroup who may benefit more from mindfulness training. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900028521; http://www.chictr.org.cn/showproj.aspx?proj=33474.

Association of MAD1L1 polymorphism (rs871925) with prenatal famine exposure and schizophrenia in a Chinese population: A case-control study.

Schizophrenia (SCZ) is a complex, frequently disabling psychiatric disorder. Prenatal exposure to famine, an environmental factor, plays a significant role in the cause of SCZ. We used DNA methylation related sites to analyze their association with prenatal famine exposure and SCZ risk in a Northeast Han Chinese population. A total of 967 subjects (446 patients with SCZ/521 health controls) were recruited. Five single-nucleotide polymorphisms (rs2300149 in ITIH1, rs2675956 in NGEF, rs3758543 in NT5C2, rs7003288 in NA, and rs871925 in MAD1L1) were selected and genotyped. Genotype distribution and allele frequency analysis indicated that rs871925 was significantly associated with SCZ. We also found a significant association between prenatal exposure to famine and rs871925 in the recessive model in the health control group. The generalized multifactor dimensionality reduction analysis suggested a five-locus interaction model association with the risk of developing SCZ. Our data suggested that MAD1L1 rs871925 was associated with prenatal famine exposure and SCZ susceptibility in a Northeast Han Chinese population.

Profiling of schizophrenia-associated serum peptides by MALDI-TOF-MS.

Schizophrenia is a psychiatric condition characterized by poor prognosis and severe symptoms that decrease the quality of life of patients. It is therefore important to develop rapid and reliable methods for early diagnosis. To achieve this aim, identification of accurate biomarkers will promote research into the mechanisms of schizophrenia and the design of effective diagnosis tools. Discriminative peptides in the serum of participants (277 schizophrenia patients and 294 healthy controls) were detected using the matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry (MALDI-TOF-MS). The diagnostic model for schizophrenia was validated using the ClinProTool software. Discrimination models were tested in the training set (200 schizophrenia patients and 200 healthy controls), and the robustness of the models was evaluated using the independent test set (77 cases and 94 controls). A total of 77 peaks were significantly different between schizophrenia patients and healthy controls with a signal-to-noise ratio of over 5. Among them, 35 peptides were down-regulated and 42 peptides were up-regulated in schizophrenia patients. With a cross-validation rate of 92.7% and a recognition capability rate of 96.5%, the supervised neural network comprising 25 discriminative peaks was found to be the most efficient model for schizophrenia diagnosis (sensitivity = 96.10%, specificity = 94.68%). Peptides at m/z = 2022.18 corresponded to complement C3f, and peptides at m/z = 1020.89, 1351.02, 1466.1 were identified as fragments of fibrinopeptide A. These two peptides may be potential biomarkers for schizophrenia in the Chinese population. The serum peptide levels present a potential clinical diagnostic tool for schizophrenia.

Association between social support and health-related quality of life among Chinese rural elders in nursing homes: the mediating role of resilience.

PURPOSE: This study aims to confirm the relationship between social support and health-related quality of life (HRQOL) among rural Chinese elders in nursing homes, and to examine the mediating role of resilience in the impact of social support on HRQOL. METHODS: A cross-sectional survey of 205 elders aged 60 and above was conducted in five rural public nursing homes. Sociodemographic characteristics, the SF-36 questionnaire, and information about social support and resilience were collected. The researchers administered the questionnaires to the participants in a face-to-face setting. Descriptive analysis and a correlation matrix were used to indicate characteristics of the participants and bivariate correlations, respectively. The mediation analyses, composed of regression analysis and PROCESS analysis, were preformed to test both direct and indirect effects of social support on HRQOL, namely the mediating role of resilience. RESULTS: Social support was positively related to HRQOL (ß = 0.303, p < 0.001) among Chinese rural elders in nursing homes. The mediating role of resilience in the relationship between social support and HRQOL was confirmed (a*b bootstrapped 95% confidence interval = [0.098, 0.257]), which revealed that social support had an indirect effect on HRQOL through resilience. CONCLUSIONS: Resilience partially mediates the relationship between social support and HRQOL. The mediation model provides a better understanding of how social support and resilience work together to affect HRQOL, and it could guide the interventions in health care for promoting HRQOL among Chinese rural elders in nursing homes.