Chau-Shoun Lee

Variant GADL1 and response to lithium therapy in bipolar I disorder.

BACKGROUND Lithium has been a first-line choice for maintenance treatment of bipolar disorders to prevent relapse of mania and depression, but many patients do not have a response to lithium treatment. METHODS We selected subgroups from a sample of 1761 patients of Han Chinese descent with bipolar I disorder who were recruited by the Taiwan Bipolar Consortium. We assessed their response to lithium treatment using the Alda scale and performed a genomewide association study on samples from one subgroup of 294 patients with bipolar I disorder who were receiving lithium treatment. We then tested the single-nucleotide polymorphisms (SNPs) that showed the strongest association with a response to lithium for association in a replication sample of 100 patients and tested them further in a follow-up sample of 24 patients. We sequenced the exons, exon-intron boundaries, and part of the promoter of the gene encoding glutamate decarboxylase-like protein 1 (GADL1) in 94 patients who had a response to lithium and in 94 patients who did not have a response in the genomewide association sample. RESULTS Two SNPs in high linkage disequilibrium, rs17026688 and rs17026651, that are located in the introns of GADL1 showed the strongest associations in the genomewide association study (P=5.50×10(-37) and P=2.52×10(-37), respectively) and in the replication sample of 100 patients (P=9.19×10(-15) for each SNP). These two SNPs had a sensitivity of 93% for predicting a response to lithium and differentiated between patients with a good response and those with a poor response in the follow-up cohort. Resequencing of GADL1 revealed a novel variant, IVS8+48delG, which lies in intron 8 of the gene, is in complete linkage disequilibrium with rs17026688 and is predicted to affect splicing. CONCLUSIONS Genetic variations in GADL1 are associated with the response to lithium maintenance treatment for bipolar I disorder in patients of Han Chinese descent. (Funded by Academia Sinica and others.).

Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year repeated cross-sectional survey

BACKGROUND Macrosocial changes might affect mental health. We investigated whether the prevalence of common mental disorders (CMDs) changed over a 20-year period of industrialisation in Taiwan. METHODS We used the 12-item Chinese Health Questionnaire to assess mental status of Taiwanese adults in 1990, 1995, 2000, 2005, and 2010. Respondents with scores of 3 or higher were classified as having probable CMDs. We assessed trends of probable CMDs with the Cochran-Armitage test and their risk factors (sex, age, marital status, educational level, employment status, and physical health) with multivariable logistic regression. The trends were compared with national rates of unemployment, divorce, and suicide. FINDINGS Of 10,548 respondents, 9079 (86·1%) completed questionnaires. The prevalence of probable CMDs doubled from 11·5% in 1990 to 23·8% in 2010 (time trend p<0·001). Increases paralleled rises in national rates of unemployment, divorce, and suicide at all five timepoints. Significant risk factors for probable CMDs were female sex (adjusted odds ratio 1·6, 95% CI 1·4-1·8), 6 or fewer years of education (1·3, 1·1-1·5), unemployment (1·4, 1·1-1·7), and poor physical health that limited daily activities (6·5, 5·4-8·0). When we controlled for these factors in multivariable models, the time trends remained significant (p<0·0001). INTERPRETATION National rates of unemployment, divorce, and suicide increased in parallel with prevalence of probable CMDs in Taiwan. Therefore, clinical and social preventive measures both seem important during times of change to the economy and labour market. FUNDING Taiwan National Science Council.

Integrative epigenetic profiling analysis identifies DNA methylation changes associated with chronic alcohol consumption

Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. Emerging evidence supports the association between DNA methylation and alcoholism, though very few studies have examined the effect of chronic alcohol consumption on the epignome. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan. The 993 aboriginal people who underwent the phase 1 (1986) clinical interviews were followed up through phase 2 (1990-1992), and phase 3 (2003-2009). Selected individuals for the current study included 10 males from the phase 1 normal cohort who remained normal at phase 2 and became dependent on alcohol by phase 3 and 10 control subjects who have not had any drinking problems throughout the study. We profiled the DNA methylation changes in the blood samples collected at phases 2 and 3. Enrichment analyses have identified several biological processes related to immune system responses and aging in the control group. In contrast, differentially methylated genes in the case group were mostly associated with susceptibility to infections, as well as pathways related to muscular contraction and neural degeneration. The methylation levels of six genes were found to correlate with alcohol consumption. These include genes involved in neurogenesis (NPDC1) and inflammation (HERC5), as well as alcoholism-associated genes ADCY9, CKM, and PHOX2A. Given the limited sample size, our approach uncovered genes and disease pathways associated with chronic alcohol consumption at the epigenetic level. The results offer a preliminary methylome map that enhances our understanding of alcohol-induced damages and offers new targets for alcohol injury research.

Development of a chinese version of the Yale-Brown obsessive compulsive scale for heavy drinking.

BACKGROUND Measurement of craving is an important component in the investigation of the etiology and clinical pictures of alcoholism and dependence of other substances in different cultures. The aim of this study was to develop a Chinese version of the Yale-Brown Obsessive Compulsive Scale for heavy drinking (YBOCS-hd-C), the instrument most frequently used in assessing the severity of alcohol craving in Taiwan. METHODS Four hundred twenty Han Chinese (220 with alcohol use disorders) and 218 Bunun aborigines (150 with alcohol use disorders) in Taiwan were interviewed by mental health professionals with the YBOCS-hd-C and a Chinese version of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry to establish the psychiatric diagnosis. Validity and reliability of the YBOCS-hd-C were examined. RESULTS The YBOCS-hd-C was found to have acceptable interrater reliability (intraclass correlation, 0.89-0.96), internal consistency (Cronbachs alpha = 0.99), construct validity, concurrent validity, and cross-cultural validity. The correlations between 10 items of the YBOCS-hd-C and 11 items of the World Health Organization Schedules for Clinical Assessment in Neuropsychiatry adjusted for age, gender, and ethnicity ranged from 0.39 to 1.00. The YBOCS-hd-C also discriminated effectively among individuals with alcohol dependence, alcohol abusers, and normal drinkers. CONCLUSIONS This study demonstrated that the YBOCS-hd-C is a reliable and valid instrument for assessing the extent of craving for alcohol in Taiwanese Han and Bunun individuals.

Risk of suicide within 1 year of cancer diagnosis: Cancer and suicide

The association of the risk of suicide with cancer at different time points after a new cancer diagnosis is unclear. This study explored the suicide hazard at different time points after a first cancer diagnosis during the 1‐year period before suicide. This case–crossover study included 2,907 suicide cases from 2002 to 2012 in Taiwan and compared the odds of suicide risk at different time points during one year after any cancer diagnosis with self‐matched periods. The 13th month preceding the suicide date was used as the control period, and the hazard period was the duration from the 1st to 12th month in the conditional logistic regression for case–crossover comparisons. Among major groups of cancers, group of lip, oral cavity and pharynx cancers tended to have higher risk of suicide than other groups of cancers. The first month of cancer diagnosis was associated with the highest risk of suicide compared with the 13th month before suicide. The odds ratio (OR) of suicide were significantly in the first six months after cancer diagnosis but declined afterwards. For example, the adjusted OR was 3.47 [95% confidence interval (CI) = 2.60–4.62] in the first month and 1.53 (95% CI = 1.11–2.12) in the sixth month following cancer diagnosis. These findings provide clinicians with a vital reference period during which sufficient support and necessary referral to mental health support should be provided to reduce the risk of suicide among patients with newly diagnosed cancer morbidity.

GADL1 variant and medication adherence in predicting response to lithium maintenance treatment in bipolar I disorder

Background Genetic variants and medication adherence have been identified to be the main factors contributing to lithium treatment response in bipolar disorders. Aims To simultaneously examine effects of variant glutamate decarboxylase-like protein 1 (GADL1) and medication adherence on response to lithium maintenance treatment in Han Chinese patients with bipolar I (BPI) disorder. Method Frequencies of manic and depressive episodes between carriers and non-carriers of the effective GADL1 rs17026688 T allele during the cumulative periods of off-lithium, poor adherence to lithium treatment and good adherence to lithium treatment were compared in Han Chinese patients with BPI disorder (n=215). Results GADL1 rs17026688 T carriers had significantly lower frequencies of recurrent affective episodes than non-T carriers during the cumulative period of good adherence, but not during those of poor adherence. Conclusions GADL1 rs17026688 and medication adherence jointly predict response to lithium maintenance treatment in Han Chinese BPI patients. Declaration of interest None. Copyright and usage

Do stillbirth, miscarriage, and termination of pregnancy increase risks of attempted and completed suicide within a year? A population-based nested case-control study

To investigate the risks of attempted and completed suicide in women who experienced a stillbirth, miscarriage, or termination of pregnancy within 1 year postnatally and compare this risk with that in women who experienced a live birth.

MicroRNA and gene expression profiling of response to lithium treatment for bipolar I disorder

Bipolar is a debilitating mood disorder characterized by mixed episodes of depression and mania. It is classified into bipolar I and II according to the occurrences and frequencies of depressive and manic episodes. As the sixth leading cause of disability in the world, bipolar disorder exerts a huge amount of burden on the patients family and the society as a whole. Lithium is often the prescribed medication; however, not all patients are responsive to it. In fact, some may even develop adverse drug reactions to the drug. In an attempt to understand the mechanisms underlying the response to lithium among bipolar I patients, we profiled the gene and microRNA expression differences between the good and poor responders in peripheral blood. We identified a number of differentially expressed genes and microRNAs, determined their functions using gene ontology and pathway annotation tools, and assessed the potential interactions between these two types of molecules via target prediction algorithms, association analyses, and existing literature evidence. We found several microRNA-gene interaction biomarkers that differ between the poor and good lithium responders. With future validations, these biomarkers may provide insights into the mechanism underlying lithium response.

Epigenetic profiling of DNA methylation changes associated with chronic alcohol consumption: A 12-year follow-up study

Alcoholism has always been a major public health concern in Taiwan, especially in the aboriginal communities. DNA methylation has recently been found to be associated with alcoholism. Since 1986, we have been following up on the mental health conditions of four major aboriginal peoples of Taiwan. In the current study, we attempted to profile the effect of chronic alcohol exposure on the epigenome. Clinical interviews were performed on 993 aboriginal people at phase 1 (1986), and followed up through phase 2 (1990-1992), and phase 3 (2003-2009) with DNA preparations at phases 2 and 3. Selected individuals for the present study included males from the phase 1 normal cohort who remained normal at phase 2 and became dependent on alcohol by phase 3 (n=10) and control subjects that have not had any drinking problems throughout the study (n=10). We assessed changes in DNA methylation in the blood collected at phases 2 and 3. Preliminary data show that 201 and 254 genes contain sites that are differentially methylated between the two collection time points in the control and case subjects, respectively. Among the list of genes differentially methylated in the case group, the methylation levels of 6 genes were found to correlate with alcohol consumption. These include genes involved in neurogenesis (NPDC1) and inflammation (HERC5) as well as alcoholism-associated genes ADCY9, CKM, and PHOX2A. Our study identified genes that are associated with chronic alcohol consumption at the epigenetic level. The results offer a comprehensive epigenomic map that helps enhance our understanding of alcohol-induced damages.

Value of supply chain management of Taiwan’s hospitality industry

Abstract Running a restaurant has always been a favorite business for people in Taiwan. Especially with the blossom of leisure travel and tourism industry it has attracted even more people to this industry. However, due to lack of good management, few restaurants survive and many more go bankrupt. Therefore, in order to improve a restaurant’s chance of success and its competitiveness in the industry, one must bring in the concept of modern management. In recent years supply chain management has been seen as one aspect of modern management that can strength a company’s competitiveness and establish a trusting relationship with its suppliers and customers. Hence, effective supply chain management can help a company acquire a competitive advantage to face future challenges. This research is aimed at studying the supply chain management as a key success factor in the restaurant industry and plans to extract relevant results by way of positive research; in the hope that those results will provide industry an important niche.