Prevalence, dimensions, and correlates of excessive daytime sleepiness in community-dwelling older adults: the Yilan study, Taiwan.

BACKGROUND: Daytime sleepiness is an important health problem. However, the dimensionality of the Epworth Sleepiness Scale (ESS) in older adults remains unclear. This study aimed to determine the prevalence of ESS-defined excessive daytime sleepiness in older adults. Furthermore, the dimensionality of ESS and its respective correlates were also compared. MATERIALS AND METHODS: This is a community-based survey in which community-dwelling older adults aged ≥ 65 years participated. Excessive daytime sleepiness was assessed using the ESS and was defined as an ESS score of > 10. Exploratory factor analysis was performed to identify the ESS factors. Multiple logistic regression analysis was used to examine the independent correlates of the ESS-defined and factor-specific correlates of excessive daytime sleepiness. RESULTS: In total, 3978 older adults participated in this study. The mean age was 76.6 ± 6.7 years, with 53.8% ≥ 75 years, and 57.1% were female. The prevalence of ESS-defined excessive daytime sleepiness was 16.0%. An exploratory factor analysis revealed two factors in the ESS, which were designated as 'passive' and 'active' according to the soporific levels of ESS items loaded in each factor. Multiple logistic regression showed that male, illiteracy, depression, disability, short sleep duration and no exposure to hypnotics were risk indicators for ESS-defined excessive daytime sleepiness. However, the correlates for passive and active factor-defined excessive daytime sleepiness differ in pattern, especially in variables related to education, exercise, mental health, and sleep. CONCLUSIONS: The prevalence of ESS-defined excessive daytime sleepiness is high, and its correlates vary among older adults. This study also suggests a dual ESS structure in community-dwelling older adults.

Daytime sleepiness is prevalent in older adults.The Epworth Sleepiness Scale (ESS) has dual constructs in older adults.Correlates for excessive daytime sleepiness vary by constructs of the ESS.

Lithium response in bipolar disorder is associated with focal adhesion and PI3K-Akt networks: a multi-omics replication study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Sex difference in the association between excessive daytime sleepiness and health-related quality of life in community-dwelling older adults: The Yilan study, Taiwan.

OBJECTIVES: The association between excessive daytime sleepiness and health-related quality of life among older adults and at-risk individuals remains unclear. This study examined relationships between excessive daytime sleepiness and unfavorable health-related quality of life and explored the moderating effect of sex. STUDY DESIGN: This was a community-based study of adults aged 65 years or more. Excessive daytime sleepiness was defined as a score exceeding 10 on the Epworth Sleepiness Scale. Multiple logistic regression analyses were used to examine the relationships between excessive daytime sleepiness and health-related quality of life. The moderating effect of sex was examined by testing interaction terms. MAIN OUTCOME MEASURES: Health-related quality of life was measured using the Short Form 12 Health Survey, which includes a physical component summary and a mental component summary. Unfavorable health-related quality of life was defined as the lowest tertile of the scores for both components. RESULTS: In total, 3788 individuals participated. After controlling for covariates, older adults with excessive daytime sleepiness did not have an unfavorable physical component summary but were more likely to have an unfavorable mental component summary (odds ratio 1.96; 95 % confidence interval 1.47-2.61). When stratified by sex, excessive daytime sleepiness was associated with a poor physical component summary in men (odds ratio 1.77, 95 % confidence interval 1.00-3.13) but not in women. CONCLUSIONS: Excessive daytime sleepiness was associated with a poor mental component summary in both sexes; however, the association with a poor physical component summary was specific to men.

Multi-ancestry genome-wide association study of major depression aids locus discovery, fine mapping, gene prioritization and causal inference.

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 cohorts with 88,316 MD cases and 902,757 controls to previously reported data. This analysis used a range of measures to define MD and included samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latin American participants (32%). The multi-ancestry GWAS identified 53 significantly associated novel loci. For loci from GWAS in European ancestry samples, fewer than expected were transferable to other ancestry groups. Fine mapping benefited from additional sample diversity. A transcriptome-wide association study identified 205 significantly associated novel genes. These findings suggest that, for MD, increasing ancestral and global diversity in genetic studies may be particularly important to ensure discovery of core genes and inform about transferability of findings.

Different dimensions of daytime sleepiness predicted mortality in older adults: Sex and muscle power-specific risk in Yilan Study, Taiwan.

OBJECTIVES: This study aimed to investigate the relationship between daytime sleepiness and mortality risk among older adults. The moderating effects of sex and physical function were examined. METHODS: This 9-year follow-up study was conducted with community-dwelling individuals aged ≥65 years. Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Exploratory factor analysis (EFA) was used to examine the ESS factors. Handgrip strength was measured to assess physical function, and the highest quartile was defined as good muscle power. Cox regression analysis was used to estimate the 9-year all-cause mortality risk. The interaction terms were examined to evaluate their moderating effect. RESULTS: In total, 2588 individuals participated in the study. The EFA explored two factors: the passive factor (PF) and the active factor (AF). After controlling for various covariates, the cutoff-defined daytime sleepiness (ESS≥11), total raw scores, and factor scores of the ESS all failed to predict mortality risk. The 3-way interaction terms showed statistical significance in terms of [sex × PF × muscle power (p = 0.03)] but not for [sex × AF × muscle power (p = 0.11)]. Specifically, PF predicted mortality risk in women with good muscle power (hazard ratio (HR): 1.48; 95 % confidence interval (CI): 1.04-2.10), which is female-specific. In contrast, AF predicted mortality risk only in men with good muscle power (HR: 1.35; 95 % CI: 1.02-1.78). CONCLUSIONS: The ESS-measured daytime sleepiness in older adults is multidimensional. The mortality risk for each dimension was determined based on sex and physical function.

The differential pattern of associations between nighttime sleep disturbances with dimensions of daytime sleepiness in community-dwelling older adults, the Yilan study, Taiwan.

BACKGROUND: The association between nighttime sleep disturbance and daytime sleepiness remains unclear. This study aimed to examine the relationships between various domains of nighttime sleep disturbance, daytime sleepiness, and their specific dimensions. METHODS: This was a community-based cross-sectional study. The participants were adults aged 65 years and older from Yilan City, Taiwan. Daytime sleepiness (DS) was defined using the Epworth Sleepiness Scale (ESS) with scores ≥ 11. The ESS dimensions were further examined using exploratory factor analysis. The highest 15% factor scores for each factor were defined as factor-specific DS. Various domains of nighttime sleep disturbance were assessed using the Pittsburgh Sleep Quality Index. Logistic regression analysis was used to examine the independent relationships among various nighttime sleep disturbances, ESS, and its dimensions. RESULTS: Of the 2585 participants, a total of 59.0% were women. Two factors were identified by exploratory factor analysis and were designated as 'passive factor' and 'active factor'. Multiple logistic regression analyses elucidated that short sleep duration was a common risk indicator for ESS-defined (odds ratio (OR): 2.01; 95% confidence interval (CI): 1.43-2.83), passive factor-defined (OR: 2.23, 95% CI: 1.65-3.00), and active factor-defined DS (OR: 1.47, 95% CI: 1.07-2.00). Hypnotic use was associated with a lower risk of both ESS-defined (OR: 0.66, 95% CI: 0.47-0.92) and passive factor-defined DS (OR:0.69, 95% CI: 0.52-0.92). Bathroom use (OR: 1.41, 95% CI: 1.04-1.91), coughing or snoring (OR: 2.14, 95% CI: 1.01-4.56), and sleep efficiency (OR: 0.42; 95% CI: 0.31-0.57) were uniquely associated with active factor-defined DS. CONCLUSION: Two factors were identified in the ESS, revealing factor-specific correlates of DS. Specifically, ESS- and passive factor-defined DS shared similar correlates. In contrast, some correlates seem unique to active-factor-defined DS.

Exploring the genetics of lithium response in bipolar disorders.

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N=2,064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. Results: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. Conclusions: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

Handgrip strength is associated with mortality in community-dwelling older adults: the Yilan cohort study, Taiwan.

INTRODUCTION: Hand grip strength (HGS) is one of the methods to help early identification of physical frailty and sarcopenia, the major concerns in the aging societies. It is also crucial to evaluate its impact on mortality. However, the available evidence regarding such impact among specific age cohorts (65 to 74 years and above) is limited. This study tried to investigate the relationship between HGS and mortality among specific cohorts of the community-dwelling older individuals in Yilan, Taiwan. METHODS: A seven-year longitudinal follow-up study was conducted involving 2,468 community-dwelling older individuals in Yilan. The participants were divided into two groups based on their quartiles of hand grip strength: with poor HGS and with good HGS. The association between HGS and mortality was examined using Cox proportional hazards models. RESULTS: The analysis revealed that age, HGS, gender, medical history of cardiovascular diseases, body mass index, and wrist-hip ratio had significant impacts on seven-year survival. Specifically, individuals with poor HGS exhibited increased mortality, with an adjusted hazard ratio (HR) of 1.87 (95% CI: 1.52-2.30). Furthermore, the adverse effect of poor HGS on mortality was more pronounced in males aged 65-74 years (adjusted HR 4.12, 95% CI: 2.16-7.84), females aged 75 years or older (2.09, 1.43-3.04) and males aged 75 years or older (1.49, 1.07-2.07). CONCLUSION: Poor hand grip strength is an independent risk factor for mid-term mortality among community-dwelling older individuals in Yilan. The assessment of HGS can serve as a valuable tool in identifying older individuals at higher risk of death.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.

Longitudinal Outcomes of Resilience, Quality of Life, and Community Integration in Treatment-Resistant Depression: A Two-Group Matched Controlled Trial.

BACKGROUND: Current evidence of nonpharmacological intervention for patients with treatment-resistant depression (TRD) is lacking. AIMS: To examine whether an 8-week nurse-led cognitive-behavioral based group intervention would enhance resilient coping and life quality among community-based patients with TRD. METHOD: The participants were randomly sampled from a cohort of TRD recruited from two general teaching hospitals. The two groups were assessed with multiple outcome measures at baseline (T0); 8-week post-baseline (T1); and at 3, 6, and 9 months after T1 (T2-4). Psychoeducation was nested in the cognitive behavioral group intervention to facilitate discussion. RESULTS: Of the 23 participants (mean age 56 years, 69.6% female) in the experimental group, higher resilient coping and lower mental distress levels at T1 as well as later improved quality of life and community integration at T2-4 were observed compared to the controls across COVID-19 (T3). Overall, the scores of resilience and community integration were higher throughout the four follow-up points of observations for the experimental group. CONCLUSION: The findings indicated that an 8-week nurse-led cognitive-behavioral based group intervention may enhance the TRD patients' resilient coping and mental distress levels while providing the potentials for community reintegration after mental health psychoeducation engagement. It is imperative for the nurses caring for patients with TRD to extend from clinical-based intervention to community-based self-care approach, with the importance of short-term stress management and healthy lifestyle development highlighted during the community reintegration trajectory.

Concurrence of Insomnia and Daytime Sleepiness Predicted 9-Year Mortality Risk in Community-Dwelling Older Adults: The Yilan Study, Taiwan.

BACKGROUND: Co-occurring insomnia and daytime sleepiness has an undetermined clinical significance in older adults. We aimed to investigate the relationship between various combinations of insomnia and daytime sleepiness with mortality risk in community-dwelling older adults. The moderation effect of sex was also assessed. METHODS: We conducted this follow-up study including community-dwelling adults aged ≥65 in Yilan City, Taiwan. Daytime sleepiness was defined as scoring ≥11 on the Epworth Sleepiness Scale. Insomnia was defined as scores ≥5 on the Athens Insomnia Scale-5. Four phenotypes were defined based on the presence of insomnia or daytime sleepiness. The 9-year mortality risks for various phenotypic combinations were estimated using Cox regression analysis. Sex-specific risks were examined using an interaction term. RESULTS: In total, 2 702 older adults participated in the study, and 59.1% were women. The total 9-year mortality rate was 27.5%. After adjusting for all covariates, compared with those without insomnia or daytime sleepiness, the phenotype of co-occurring insomnia with daytime sleepiness predicted higher mortality risk (hazard ratio [HR]: 1.76, confidence interval [CI]: 1.20-2.58). In contrast, insomnia and daytime sleepiness alone did not correlate with higher mortality. The interaction between sex with co-occurring insomnia and daytime sleepiness was significant (p = .01). When stratifying by sex, the association between co-occurring insomnia and daytime sleepiness with higher mortality risk was male-specific (HR: 3.07, CI: 1.87-5.04). CONCLUSIONS: Concurrence of insomnia and daytime sleepiness indicates a toxic phenotypic combination in older adults, particularly in men. Precise public health and preventive medicine can be implemented through geriatric sleep medicine.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder.

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi+Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1×10- 4 values, including HAS3, CNTNAP5 and NFIB. Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3ß. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4, XKR4, NRXN1, NRG1/3 and GRK5. Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level.

The association between bedtime and cardiac autonomic control in community-dwelling older adults - The Yilan study, Taiwan.

This study aimed to investigate the association between bedtime and cardiac autonomic function in older adults. This cross-sectional study included community-dwelling older adults aged ≥ 65 years. Self-reported bedtime was categorized as early (< 21:30), intermediate (21:30-22:30), and late (> 22:30). Cardiac autonomic function was evaluated by HRV. The lowest tertiles for each HRV parameter were defined as unhealthy indicators. A total of 3,729 individuals participated, with mean age of 76.3 ± 6.6 years. After controlling for various covariates, late bedtime was associated with a lower risk for unhealthy total power [Odds ratio (OR) = 0.74; 95% confidence interval (CI) = 0.59-0.93] and low frequency power (OR = 0.69, 95% CI = 0.55-0.87) than intermediate bedtime. In contrast, early bedtime was correlated with a higher risk of poor total power (OR = 1.23, 95% CI: 1.05-1.45) and high frequency power (OR = 1.18, 95% CI = 1.00-1.39). When further specifying sleep duration and physical disability into the regression models, the inverse association between late bedtime and unhealthy HRV remained; however, the association between early bedtime and HRV disappeared. Accordingly, we concluded that in terms of cardiac autonomic function, early bedtime in older adults is not necessarily beneficial for their health outcomes, whereas late bedtime may not be detrimental.Abbreviations: ADL: activity of daily living; BMI: body mass index; CI: confidence interval; GARS: the Groningen Activity Restriction Scale; HADS: The Hospital Anxiety and Depression Scale; HF: high frequency power; HRV: heart rate variability; LF: low frequency power; LF/HF: low frequency to high frequency ratio; OR: odds ratios; TP: total power.

The associations between working conditions and subjective sleep quality among female migrant care workers.

Background: Subjective sleep quality may reflect the mental well-being of migrant care workers; however, the related occupational factors remain unclear. This study examines the association between the characteristics of care labor and the subjective sleep quality of female migrants. Methods: In this cross-sectional study, Southeast Asian migrant care workers in Taiwan were recruited using convenience sampling. Data on working conditions, including workplace setting, wage, working hours, psychiatric symptoms of care recipients, and sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI), were collected through computer-assisted personal interviews. Multiple linear regression analyses were performed to determine the independent relationship between working conditions and the PSQI global score. Results: There were 220 institution-(47.7%) and home-based (52.3%) care workers, and 47.7% had a PSQI score higher than 5. After controlling for covariates, the lowest tertile of wages and daily working hours (> 8 h) were independently correlated with poor sleep quality. Moreover, in the stepwise regression model, wage and working hours remained the most explainable correlates of poor sleep quality. Conclusion: This study lent support to the notion that low wages and long working hours are significant occupational factors that negatively impact the subjective sleep quality of female Southeast Asian migrant care workers in Taiwan.

The mediating effects of personality traits on the relationship of youth conduct problems and mood disorders with adulthood suicidality.

Identifying the relevant factors for suicidality in individuals with conduct problems is a public health concern, especially if they were under the influence of mood disorders later in life. This study investigates the relationship between youth conduct problems and mood disorders and adulthood suicidality, and to further explore the mediating effects of personality on this relationship. A retrospective cohort study was administered to 308 individuals aged 20-65 years, with or without mood disorders diagnosed by psychiatrists. The Composite International Diagnosis Interview was used to evaluate conduct problems in youth and suicidality (i.e., suicide plan and suicide attempt) in the past year. Personality traits were assessed using Eysenck Personality Questionnaire-Revised for extraversion and neuroticism. Multiple-mediator analysis was used to investigate the mediation effects of personality traits on the relationship between conduct problems and suicidality. The average age of enrolled participants was 31.6 years, and 42.5% of them were female. 39.2% reported suicidality and 43.2% reported conduct problems in youth. Participants who were diagnosed with mood disorders (p < 0.001) and reported having conduct problems (p = 0.004) were associated with high suicidality. Multiple-mediator analysis showed that conduct problems in youth increased the risk of adulthood suicidality through the indirect effects of higher neuroticism (suicide plan: OR = 1.30, BCA 95% CI = 1.04-1.83; suicide attempt: OR = 1.27, BCA 95% CI = 1.05-1.66). Neuroticism mediates the association between youth conduct problems and adulthood suicidality. This finding raises our attention to assess personality traits in individuals with youth conduct problems for designing proper intervention strategies to reduce the risk of suicide.

Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.

Characterization of clinical features and comorbidities between bipolar affective disorder with and without depressive episodes.

BACKGROUNDS: A proportion of patients with bipolar disorder (BD) manifests with only unipolar mania (UM). This study examined relevant clinical features and psychosocial characteristics in UM compared with depressive-manic (D-M) subgroups. Moreover, comorbidity patterns of physical conditions and psychiatric disorders were evaluated between the UM and D-M groups. METHODS: This clinical retrospective study (N = 1015) analyzed cases with an average of 10 years of illness duration and a nationwide population-based cohort (N = 8343) followed up for 10 years in the Taiwanese population. UM was defined as patients who did not experience depressive episodes and were not prescribed adequate antidepressant treatment during the disease course of BD. Logistic regression models adjusted for relevant covariates were used to evaluate the characteristics and lifetime comorbidities in the two groups. RESULTS: The proportion of UM ranged from 12.91% to 14.87% in the two datasets. Compared with the D-M group, the UM group had more psychotic symptoms, fewer suicidal behaviors, a higher proportion of morningness chronotype, better sleep quality, higher extraversion, lower neuroticism, and less harm avoidance personality traits. Substantially different lifetime comorbidity patterns were observed between the two groups. CONCLUSIONS: Patients with UM exhibited distinct clinical and psychosocial features compared with patients with the D-M subtype. In particular, a higher risk of comorbid cardiovascular diseases and anxiety disorders is apparent in patients with D-M. Further studies are warranted to investigate the underlying mechanisms for diverse presentations in subgroups of BDs.

Exploration of the relationship between gut microbiota and fecal microRNAs in patients with major depressive disorder.

Microbiota-gut-brain axis signaling plays a pivotal role in mood disorders. The communication between the host and the gut microbiota may involve complex regulatory networks. Previous evidence showed that host-fecal microRNAs (miRNAs) interactions partly shaped gut microbiota composition. We hypothesized that some miRNAs are correlated with specific bacteria in the fecal samples in patients with major depressive disorder (MDD), and these miRNAs would show enrichment in pathways associated with MDD. MDD patients and healthy controls were recruited to collect fecal samples. We performed 16S ribosome RNA sequence using the Illumina MiSeq sequencers and analysis of 798 fecal miRNAs using the nCounter Human-v2 miRNA Panel in 20 subjects. We calculated the Spearman correlation coefficient for bacteria abundance and miRNA expressions, and analyzed the predicted miRNA pathways by enrichment analysis with false-discovery correction (FDR). A total of 270 genera and 798 miRNAs were detected in the fecal samples. Seven genera (Anaerostipes, Bacteroides, Bifidobacterium, Clostridium, Collinsella, Dialister, and Roseburia) had fold changes greater than one and were present in over 90% of all fecal samples. In particular, Bacteroides and Dialister significantly differed between the MDD and control groups (p-value < 0.05). The correlation coefficients between the seven genera and miRNAs in patients with MDD showed 48 pairs of positive correlations and 36 negative correlations (p-value < 0.01). For miRNA predicted functions, there were 57 predicted pathways with a p-value < 0.001, including MDD-associated pathways, axon guidance, circadian rhythm, dopaminergic synapse, focal adhesion, long-term potentiation, and neurotrophin signaling pathway. In the current pilot study, our findings suggest specific genera highly correlated with the predicted miRNA functions, which might provide clues for the interaction between host factors and gut microbiota via the microbiota-gut-brain axis. Follow-up studies with larger sample sizes and refined experimental design are essential to dissect the roles between gut microbiota and miRNAs for depression.