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.

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.

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.

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.

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.

Using polygenic scores and clinical data for bipolar disorder patient stratification and lithium response prediction: machine learning approach.

BACKGROUND: Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. AIMS: To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder. METHOD: This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework. RESULTS: The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data. CONCLUSIONS: Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder.

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18-2.01) and European sample: OR = 1.75 (95% CI: 1.30-2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61-4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD.

Volunteering and self-reported health outcomes among older people living in the community: the Yilan study, Taiwan.

PURPOSE: This study aimed to explore associations between volunteering and various self-reported health outcomes among older people, including subjective physical and mental health, self-rated health, and self-rated happiness. METHODS: This questionnaire survey was conducted in Yilan, Taiwan. By convenient sampling, a total of 3692 older people living in the community were recruited from 2012 to 2016. Participants' engagement in community volunteer activities in the past month was recorded. Subjective physical and mental health were evaluated using the Short Form-12 version2 Health Survey physical and mental component summary scores. Self-rated health and happiness were each evaluated by a single question. Participants' demographic information and comorbidities were also recorded. We conducted multiple linear regression analyses adjusted for age, sex, marital status, body mass index, educational level, living status, comorbidities, smoking status, and status of alcohol drinking. RESULTSS: After adjusting for covariates, volunteering was significantly associated with better subjective physical health, self-rated health, and self-rated happiness scores (B = 2.41, 95% confidence interval [CI] (1.56, 3.26); B = 3.46, 95% CI (2.66, 4.66), and B = 4.62, 95% CI (3.18, 6.05), respectively). The strength of the relationships between volunteering and various self-reported health outcomes differed. CONCLUSIONS: Volunteering has positive associations on subjective physical health, self-rated health, and happiness for older people living in the community in Yilan, Taiwan. Further follow-up studies are needed to examine the mechanisms of associations between volunteering and various self-reported health outcomes, and clarify the differences in the strength of their associations.

Volunteer participation differentially moderates the association between insomnia and poor subjective well-being in community-dwelling older adults: the Yilan study, Taiwan.

OBJECTIVES: We aimed to elucidate the moderating effect of volunteer participation on the association between insomnia and subjective well-being. METHODS: This was a community-based, cross-sectional study that targeted community-dwelling older adults aged ≥ 65 years in Yilan city, Taiwan. Whether individuals had volunteered in the past month was asked. Insomnia was measured using the Athens Insomnia Scale-5. Subjective well-being was evaluated using self-rated health, self-rated happiness, the physical component summary (PCS), and the mental component summary (MCS) of Short-form 12. Interaction terms between volunteer participation and insomnia were examined to test the moderating effect of volunteer participation on subjective well-being. RESULTS: In total, 3,875 participants were included in the study. After controlling for confounders, older adults with insomnia were more likely to have poor subjective well-being, except with respect to PCS. By contrast, volunteering was associated with a low risk of association between self-rated health and happiness. The interaction terms for volunteering with self-rated happiness (p = 0.03) and the MCS (p = 0.02) were significant. The association between insomnia and poor self-rated happiness among volunteers (odds ratio [OR] = 3.91, 95% confidence interval [CI] = 1.85-8.28) was significantly stronger than that in non-volunteers (OR = 1.48, 95% CI = 1.18-1.86). However, insomnia was linked with poor MCS in non-volunteers (OR = 1.53, 95% CI = 1.21-1.94), but not in volunteers (OR = 0.64, 95% CI = 0.27-1.50). DISCUSSION: Volunteer participation moderated the association between insomnia and subjective well-being; specifically, volunteering strengthened the association between insomnia and poor self-rated happiness but mitigated the relationship between insomnia and poor MCS.

Depression and anxiety correlate differentially with dissatisfaction with healthcare services in older adults: The Yilan Study, Taiwan.

BACKGROUND/PURPOSE: Previous studies have seldom investigated the psychological factors that are associated with dissatisfaction with healthcare services. We therefore examined the associations of depression and anxiety with service dissatisfaction among older adults. METHODS: A community-based health survey was conducted from 2012 to 2016. Residents aged ≥65 years were randomly recruited from Yilan City, Taiwan. Besides overall dissatisfaction, we assessed dissatisfaction with physicians' ability, physicians' attitude, and waiting time. The Hospital Anxiety and Depression Scale was used to detect depressive and anxiety symptoms with optimal cut-off points of 3 for the anxiety subscale and 6 for the depression subscales. RESULTS: Of the 3480 residents included in this study, the overall dissatisfaction rate was 7.9%. After controlling for covariates, depressive and anxiety symptoms were consistently correlated with the various dimensions of dissatisfaction. More specifically, depressive symptoms were associated with overall dissatisfaction and dissatisfaction with physicians' ability and attitude. Conversely, anxiety was uniquely associated with dissatisfaction with waiting time. CONCLUSION: Psychological symptoms were consistent correlates of dissatisfaction with healthcare services among older adults, although the specific symptoms had different associations with the various dimensions of dissatisfaction.

Different item characteristics of a mild cognitive impairment screening tool in the community-based Yilan Study: application of the item response theory.

BACKGROUND: This study aimed to use item response theory (IRT) to explore the item-by-item characteristics of a mild cognitive impairment (MCI) screening tool using community-based data. METHODS: The Yilan Study is a community-based study that has been conducted since 2012. Until March 2020, 2230 older adults were interviewed according to the household registration data. IRT was applied to determine the item-by-item distinctive characteristics of the Eight-item Interview to Differentiate Aging and Dementia (AD8). RESULTS: The MCI characteristics in the AD8 items have varying degrees of item response threshold. In all circumstances, item AD8-8, which is related to self-rated memory ability, had a low item response threshold. AD8-5 and AD8-7, which are related to the comparisons of time-oriented functional status, had slightly lower thresholds, especially for those aged 65-79 years or without activity limitations. Conversely, AD8-1, AD8-2, AD8-3, AD8-4, and AD8-6 had similar item response thresholds and discriminative power; these items have more detailed functional descriptions or examples for illustration. CONCLUSIONS: Concise and understandable elements are often expected in community-based screening tools. For community-based health screening and population empowerment in the early detection of MCI, assessment tool items with detailed functional descriptions and examples for illustration have similar validities in most of the population. Items related to self-rated memory ability might be less valid. More examples may be needed for items constructed for comparing time-oriented functional status, especially in extremely old adults and individuals with activity limitations.

Hand grip strength in predicting the risk of osteoporosis in Asian adults.

INTRODUCTION: There is a need for a cost-effective method to identify individuals with a high risk of osteoporosis. This study aimed to investigate the suitability of hand grip strength in predicting the risk of osteoporosis in Asian adults. MATERIALS AND METHODS: In this cross-sectional, hospital-based study of 1007 participants, the bone mineral density of the spine and hips was evaluated using dual-energy X-ray absorptiometry according to the 2019 International Society for Clinical Densitometry official positions. Bone microarchitecture was evaluated using the trabecular bone score, and hand grip strength was measured in the dominant hand using a hand digital dynamometer. RESULTS: Hand grip strength was significantly related to bone density and bone microarchitecture. Moreover, hand grip strength was a significant predictor of osteoporosis in both women and men. For osteoporosis prediction in women, a threshold of 21.9 kg of hand grip strength had a sensitivity of 59%, specificity of 59%, and area under the curve (AUC) of 0.61. In men, a threshold of 28.7 kg had a sensitivity of 66%, specificity of 78%, and AUC of 0.75. The optimal cutoff strengths for osteoporosis depended on age and sex. CONCLUSION: The measurement of hand grip strength is a simple, cost-effective and an easy assessment method for identifying individuals at a high risk of osteoporosis. The cutoff strength for evaluating osteoporosis in adults is age and sex specific.

Using hand grip strength to detect slow walking speed in older adults: the Yilan study.

BACKGROUND: Walking speed is an important health indicator in older adults, although its measurement can be challenging because of the functional decline due to aging and limited environment. The aim of this study was to examine whether hand grip strength can be a useful proxy for detecting slow walking speed in this population. METHODS: A cross-sectional study was conducted using the cohort from the Yilan Study in Taiwan. Community-dwelling older adults aged 65 years and older were included. Slow walking speed was defined as a 6-meter walking speed < 1.0 m/s, according to the 2019 Asian Working Group for Sarcopenia diagnostic criteria. Stepwise multiple linear regression was used to determine the most significant variables associated with walking speed. Receiver operating characteristic analysis was used to determine the optimal cutoff values for hand grip strength in detecting slow walking speed. RESULTS: A total of 301 participants with an average age of 73.9 ± 6.8 years were included; 55.1 % participants were women. In stepwise multiple linear regression analysis that included various variables, hand grip strength was found to be the most explainable factor associated with walking speed among all participants and among participants of each sex. The optimal cutoff values for hand grip strength in the detection of slow walking speed were 19.73 kg for all participants (sensitivity: 55 %, specificity: 83 %, area under the curve: 0.74, accuracy: 66.9 %), 35.10 kg for men (sensitivity: 92 %, specificity: 42 %, area under the curve: 0.70, accuracy: 66.4 %), and 17.93 kg for women (sensitivity: 62 %, specificity: 80 %, area under the curve: 0.76, accuracy: 67.9 %). CONCLUSIONS: Hand grip strength was found to be a useful proxy for the identification of slow walking speed in older adults.

Investigation of early and lifetime clinical features and comorbidities for the risk of developing treatment-resistant depression in a 13-year nationwide cohort study.

BACKGROUND: To investigate the risk of treatment-resistant depression (TRD) in patients with depression by examining their clinical features, early prescription patterns, and early and lifetime comorbidities. METHODS: In total, 31,422 depressive inpatients were followed-up from diagnostic onset for more than 10-years. Patients were diagnosed with TRD if their antidepressant treatment regimen was altered ≥two times or if they were admitted after at least two different antidepressant treatments. Multiple Cox regression model were used to determine whether physical and psychiatric comorbidities, psychosis, and prescription patterns increased the risk of TRD by controlling for relevant demographic covariates. Survival analyses were performed for important TRD-associated clinical variables. RESULTS: Females with depression (21.24%) were more likely to suffer from TRD than males (14.02%). Early anxiety disorders were more commonly observed in the TRD group than in the non-TRD group (81.48 vs. 58.96%, p < 0.0001). Lifetime anxiety disorders had the highest population attributable fraction (42.87%). Seventy percent of patients with multiple psychiatric comorbidities developed TRD during follow-up. Cox regression analysis further identified that functional gastrointestinal disorders significantly increased TRD risk (aHR = 1.19). Higher doses of antidepressants and benzodiazepines and Z drugs in the early course of major depressive disorder increased TRD risk (p < 0.0001). CONCLUSION: Our findings indicate the need to monitor early comorbidities and polypharmacy patterns in patients with depression associated with elevated TRD risk.

The associations between various sleep-wake disturbances and depression in community-dwelling older adults- the Yilan study, Taiwan.

Objectives: Given the close relationship between sleep-wake disturbances and depression, an in-depth investigation of such a relationship is imperative. The present study aims at elucidating the relationship between various sleep-wake disturbances and depression in older adults and at examining the influence of co-occurring anxiety on such associations.Method: A community-based survey using the cohort from the Yilan Study in Taiwan was conducted from August 2013 to November 2016. Adults aged 65 and older were randomly selected to participate in the study. The Hospital Depression and Anxiety Scale was used to measure clinical depressive and anxiety symptoms. Insomnia and daytime sleepiness were defined through the Athens Insomnia Scale and the Epworth Sleepiness Scale, respectively. Furthermore, the use of hypnotics, subjective sleep duration and sleep-wake scheduling were evaluated. Their relationship with depression was examined through logistic regression analyses.Results: There were 2620 participants surveyed and 247 (9.4%) had depression. Before controlling for anxiety, insomnia (OR: 1.78, 95% CI: 1.23-2.55), daytime sleepiness (OR: 1.79, 95% CI: 1.27-2.53), and long sleepers (OR: 1.77, 95% CI: 1.24-2.53) have a higher likelihood for depression in the multivariable regression analysis. However, when including anxiety into the multivariable regression model, only those with daytime sleepiness and long sleepers had an elevated risk for depression. Therefore, the association between insomnia and depression turned to be statistically non-significant.Conclusion: In older adults, various sleep-wake disturbances differ in their relationship with depression. In addition, daytime sleepiness and long sleep duration were mostly characteristic of depression when co-occurring anxiety was considered.

Relationship between muscle strength and fall episodes among the elderly: the Yilan study, Taiwan.

BACKGROUND: Fall episodes are not unusual among community residents, especially the elderly, and lower muscle strength is an important issue to address in order to prevent falls. METHODS: A community health survey was conducted in a suburban area of Taiwan, and 1067 older adults were selected for enrollment in the present study. All the enrolled subjects had been visited at their homes; the subjects' strength of both hands and muscle mass of both legs were measured and well-established questionnaires were finished by certificated paramedic staffs. RESULTS: The incidence of fall episodes in the previous 1 year in the Yilan elderly population was 15.1%, and the female predominance was significant. A significantly higher prevalence of cataracts was found in group who experienced a fall in the past year (64% vs. 54.9% in the non-fall group). Mild or more severe dementia was much more prevalent in the group who experienced a recent fall (33.8% vs. 25.7% in the non-fall group). The strength of both hands tested as the physical function was 17.6 ± 8.0 kg in the recent fall group, significantly weaker than that in the non-fall group (20.7 ± 8.7 kg). Multivariate regression analysis revealed a greater weekly exercise duration and greater strength of both hands reduced the occurrence of falls among the whole and the female population. The standardized effect sizes of hand grip strength between both groups, not trivial, were 0.29 and 0.37 for the total population and the female subpopulation respectively. CONCLUSIONS: Less weekly exercise duration and weaker muscle strength were f ound to be independent risk factors of fall episode(s) in an elderly Taiwanese population, especially in the female sub-population. Muscle strength, measured by average of both hands grip strength, was the most significantly factor of one-year fall episode(s) accessed retrospectively.

Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study.

BACKGROUND: Lithium is a first-line treatment in bipolar disorder, but individual response is variable. Previous studies have suggested that lithium response is a heritable trait. However, no genetic markers of treatment response have been reproducibly identified. METHODS: Here, we report the results of a genome-wide association study of lithium response in 2563 patients collected by 22 participating sites from the International Consortium on Lithium Genetics (ConLiGen). Data from common single nucleotide polymorphisms (SNPs) were tested for association with categorical and continuous ratings of lithium response. Lithium response was measured using a well established scale (Alda scale). Genotyped SNPs were used to generate data at more than 6 million sites, using standard genomic imputation methods. Traits were regressed against genotype dosage. Results were combined across two batches by meta-analysis. FINDINGS: A single locus of four linked SNPs on chromosome 21 met genome-wide significance criteria for association with lithium response (rs79663003, p=1·37 × 10(-8); rs78015114, p=1·31 × 10(-8); rs74795342, p=3·31 × 10(-9); and rs75222709, p=3·50 × 10(-9)). In an independent, prospective study of 73 patients treated with lithium monotherapy for a period of up to 2 years, carriers of the response-associated alleles had a significantly lower rate of relapse than carriers of the alternate alleles (p=0·03268, hazard ratio 3·8, 95% CI 1·1-13·0). INTERPRETATION: The response-associated region contains two genes for long, non-coding RNAs (lncRNAs), AL157359.3 and AL157359.4. LncRNAs are increasingly appreciated as important regulators of gene expression, particularly in the CNS. Confirmed biomarkers of lithium response would constitute an important step forward in the clinical management of bipolar disorder. Further studies are needed to establish the biological context and potential clinical utility of these findings. FUNDING: Deutsche Forschungsgemeinschaft, National Institute of Mental Health Intramural Research Program.

Comparison of associated features and drug treatment between co-occurring unipolar and bipolar disorders in depressed eating disorder patients.

BACKGROUND: To examine the differences of associated characteristics and prescription drug use between co-occurring unipolar and bipolar disorders in patients with eating disorders (EDs). METHODS: Patients with EDs and major depressive episode (MDE) were recruited from psychiatric outpatient clinics. They were interviewed and completed self-administered measures assessing eating and general psychopathology. The prescribed drugs at the index outpatient visit were recorded. Clinical characteristics and prescription drugs of groups with major depressive disorder (ED-MDD), MDE with lifetime mania (ED-BP I), and MDE with lifetime hypomania (ED-BP II) were compared. Continuous variables between groups were compared using generalized linear regression with adjustments of age, gender, and ED subtype for pair-wise comparisons. Multivariate logistic regression with adjustments of age, gender, and ED subtype was employed to estimate adjusted odds ratios with 95% confidence intervals between groups. RESULTS: Two hundred and twenty-seven patients with EDs had a current MDE. Among them, 17.2% and 24.2% experienced associated manic and hypomanic episodes, respectively. Bipolar I and II patients displayed significantly poorer weight regulation, more severe impulsivity and emotional lability, and higher rates of co-occurring alcohol use disorders than ED-MDD patients. ED-BP I patients were found to have the lowest IQ, poorest working memory, and the most severe depression, suicidality and functional impairment among all patients. Patients with ED-BP II shared affect and behavioral dysregulations with ED-BP I, but had less severe degrees of cognitive and functional impairments than ED-BP I. Patients with ED-BP I were significantly less likely than those in the ED-MDD and ED-BP II groups to be on antidepressant monotherapy, but a great rate (27%) of ED-BP I individuals taking antidepressant monotherapy had potential risk of mood switch during the course of treatment. CONCLUSIONS: Our study identified discriminative features of bipolar I and II disorders from MDD among a group of depressed ED patients. We suggest that the associated mania, hypomania, and mood lability are predictors of clinical severity and should be identified from ED patients presented with depressive features. Accurate diagnosis of bipolar disorders may have implications for pharmacotherapy in patients with EDs.

Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies.

BACKGROUND: This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. METHODS: We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. RESULTS: Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P<5.0×10-6), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P<6.0×10-3) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P=3.9×10-4~1.0×10-3) and replication samples (2.8×10-4~1.7×10-3). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II. CONCLUSION: We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II.

Correlates of self-report chronic insomnia disorders with 1-6 month and 6-month durations in home-dwelling urban older adults - the Shih-Pai Sleep Study in Taiwan: a cross-sectional community study.

BACKGROUND: To examine the correlates of insomnia disorder with different durations in home-dwelling older adults. METHODS: A cross-sectional survey in the Shih-Pai area of Taipei City, Taiwan (The Shih-Pai Sleep Study). A total 4047 subjects over the age of 65 years completed the study (2259 men and 1788 women). The Pittsburgh Sleep Quality Index and the duration of insomnia symptoms were used to identify DSM-IV 1-6 month and 6-month insomnia disorders. RESULTS: The prevalence of DSM-IV defined insomnia disorder was 5.8 %; two-thirds of these case lasted for ≥6 months. The shared correlates for both 1-6 and 6-month insomnia disorders were gender (women), depression and moderate pain. Pulmonary diseases were exclusively associated with 1-6 month insomnia disorder (OR: 2.57, 95 % CI: 1.46-4.52). In contrast, heart disease (OR: 1.73, 95 % CI: 1.21-2.49) and severe pain (OR: 2.34, 95 % CI: 1.14-4.40) were associated with 6-month insomnia disorder. CONCLUSION: The prevalence of persistent insomnia disorder is higher than short-term insomnia disorder. Correlates for less persistent and more persistent insomnia disorder appears to be partially different. Duration quantifiers may be important in the identification of the etiology of insomnia and further studies with follow-ups are needed to examine the order of developing insomnia disorder and associated conditions.