Chung-Ying Chen

Genome-wide association study of bipolar I disorder in the Han Chinese population

We report the first genome-wide association study in 1000 bipolar I patients and 1000 controls, with a replication of the top hits in another 409 cases and 1000 controls in the Han Chinese population. Four regions with most strongly associated single-nucleotide polymorphisms (SNPs) were detected, of which three were not found in previous GWA studies in the Caucasian populations. Among them, SNPs close to specificity protein 8 (SP8) and ST8 α-N-acetyl- neuraminide α-2,8-sialyltransferase (ST8SIA2) are associated with Bipolar I, with P-values of 4.87 × 10−7 (rs2709736) and 6.05 × 10−6 (rs8040009), respectively. We have also identified SNPs in potassium channel tetramerization domain containing 12 gene (KCTD12) (rs2073831, P=9.74 × 10−6) and in CACNB2 (Calcium channel, voltage-dependent, β-2 subunit) gene (rs11013860, P=5.15 × 10−5), One SNP nearby the rs1938526 SNP of ANK3 gene and another SNP nearby the SNP rs11720452 in chromosome 3 reported in previous GWA studies also showed suggestive association in this study (P=6.55 × 10−5 and P=1.48 × 10−5, respectively). This may suggest that there are common and population-specific susceptibility genes for bipolar I disorder.

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.).

Mortality and suicide after self-harm: community cohort study in Taiwan

BACKGROUND Little is known about outcomes after self-harm in East Asia. AIMS To investigate mortality after self-harm in a Taiwanese population. METHOD Between 2000 and 2003, 1083 individuals who self-harmed were identified through a population self-harm register in Nantou County, Taiwan, and followed until 2007 for date and cause of death on a national mortality database. RESULTS In total, 145 individuals died, 48 through suicide. The risks of all-cause and suicide mortality in the first year were 4.7% and 2.1% respectively, representing 8- and 131-fold age- and gender-standardised increases. Male gender and older age were independent risk factors for both suicide and non-suicide mortality. Use of more lethal methods in the index episode was associated with higher mortality but this was accounted for by gender. CONCLUSIONS Results in this sample support the recommendation that people with a history of recent self-harm should be a major target for suicide prevention programmes.

Non-fatal repetition of self-harm: population-based prospective cohort study in Taiwan

BACKGROUND Repeated self-harm is relatively common and is linked with an elevated risk of eventual suicide. There has been no study of this involving a large sample from the Far East. AIMS To estimate the risk over the medium term of non-fatal repetition of self-harm and identify predictive factors in those carrying out self-harm. METHOD A total of 970 individuals who had self-harmed were recruited from a community-based suicide behaviour register system in Nantou, Taiwan from July 2000 to February 2003. Information regarding demography and suicide methods was collected. Individuals were followed-up until December 2005 to examine the risk of repeated self-harm and independent predictive factors. RESULTS Ninety cohort members had repeated self-harm during the follow-up period (accounting for 131 repeated self-harm episodes in all). The cumulative risks were 5.7% for the first year, 7.8% for the second year and 9.5% for the fourth year. The risk was highest within the first year after the self-harm event. Independent risk factors included female gender and self-cutting as well as self-poisoning with drugs. Effect of younger age was mediated through the choice of methods. CONCLUSIONS Individuals with self-harm have a high risk of repetition, especially within the first year. Suicide prevention strategies need to focus on intervening with this population to reduce their repetition.

Effect of amphetamine on corrected-QT interval change during methadone maintenance treatment in Taiwan: A prospective cohort study

INTRODUCTION AND AIMS Previous studies have suggested that methadone is associated with prolonged corrected-QT (QTc) interval, but published prospective research studies in this area are relatively scarce. This study investigates QTc interval change among methadone maintenance patients and possible associated risk factors. One of the aims is to explore the effect of amphetamines. DESIGN AND METHODS This prospective cohort study with six-month follow up assesses the effect of methadone on QTc interval among a sample (n = 170) of heroin users in a methadone maintenance treatment program in Taiwan. Demographic data, substance use history, medical history and laboratory studies were collected at study enrollment. Twelve-lead electrocardiograms were performed for all participants both at study enrollment and six months later. RESULTS The median daily methadone dose was 41 mg. A mean increase of QTc interval (17.1 ms, SD = 50.0, P < 0.001) was found at six-month follow up. QTc interval prolongation in the sample at baseline was 2.9%, and at six months was 12.4%. A positive correlation was found between comorbid amphetamine use frequency in the past month and QTc interval change. Methadone dose was not associated with QTc change. DISCUSSION AND CONCLUSIONS An increase of mean QTc interval was found among methadone maintenance patients at six-month follow up. Electrocardiogram monitoring should be performed among patients who are at risk of frequently using amphetamines during methadone maintenance treatment.

Prevalence, correlates, and risk perception of HIV infection among heroin users in Central Taiwan

We investigated the prevalence and correlated factors of human immunodeficiency virus (HIV) among heroin users attending methadone maintenance treatment (MMT) programs in Central Taiwan, and explored the degree of risk perception of HIV infection among the participants. Our study participants were 781 heroin users seeking treatment at the MMT program at Tsaotun Psychiatric Center in Taiwan. The presence of HIV antibodies was identified by microparticle enzyme immunoassay and confirmed by western blot. Multivariate logistic regression was used to identify the independent correlates of HIV infection. The mean age of the sample was 36.1 years [standard deviation (SD) = 7.6]; of the patients, 710 (90.9%) were men. The prevalence of HIV infection among our study population was 20.7%. Multivariate logistic regression analysis revealed that HIV infection was independently associated with the age of the patients of initial heroin use, heroin injection use, nondrug‐related criminal convictions, needle‐sharing behaviors, and sharing injection paraphernalia. A strong agreement existed between self‐reported HIV serostatus and the results of laboratory analyses, with 88.8% of patients reporting their condition correctly. We found a high rate of HIV infection among patients in the MMT program. Factors associated with HIV infection were mostly related to drug‐use behaviors. These findings stress the importance of education regarding drug‐risk behaviors.

Effect of amphetamine on corrected-QT interval change during methadone maintenance treatment in Taiwan

INTRODUCTION AND AIMS Previous studies have suggested that methadone is associated with prolonged corrected-QT (QTc) interval, but published prospective research studies in this area are relatively scarce. This study investigates QTc interval change among methadone maintenance patients and possible associated risk factors. One of the aims is to explore the effect of amphetamines. DESIGN AND METHODS This prospective cohort study with six-month follow up assesses the effect of methadone on QTc interval among a sample (n = 170) of heroin users in a methadone maintenance treatment program in Taiwan. Demographic data, substance use history, medical history and laboratory studies were collected at study enrollment. Twelve-lead electrocardiograms were performed for all participants both at study enrollment and six months later. RESULTS The median daily methadone dose was 41 mg. A mean increase of QTc interval (17.1 ms, SD = 50.0, P < 0.001) was found at six-month follow up. QTc interval prolongation in the sample at baseline was 2.9%, and at six months was 12.4%. A positive correlation was found between comorbid amphetamine use frequency in the past month and QTc interval change. Methadone dose was not associated with QTc change. DISCUSSION AND CONCLUSIONS An increase of mean QTc interval was found among methadone maintenance patients at six-month follow up. Electrocardiogram monitoring should be performed among patients who are at risk of frequently using amphetamines during methadone maintenance treatment.

Effect of amphetamine on corrected-QT interval change during methadone maintenance treatment in Taiwan: A prospective cohort study: Amphetamine, methadone and QTc change

INTRODUCTION AND AIMS Previous studies have suggested that methadone is associated with prolonged corrected-QT (QTc) interval, but published prospective research studies in this area are relatively scarce. This study investigates QTc interval change among methadone maintenance patients and possible associated risk factors. One of the aims is to explore the effect of amphetamines. DESIGN AND METHODS This prospective cohort study with six-month follow up assesses the effect of methadone on QTc interval among a sample (n = 170) of heroin users in a methadone maintenance treatment program in Taiwan. Demographic data, substance use history, medical history and laboratory studies were collected at study enrollment. Twelve-lead electrocardiograms were performed for all participants both at study enrollment and six months later. RESULTS The median daily methadone dose was 41 mg. A mean increase of QTc interval (17.1 ms, SD = 50.0, P < 0.001) was found at six-month follow up. QTc interval prolongation in the sample at baseline was 2.9%, and at six months was 12.4%. A positive correlation was found between comorbid amphetamine use frequency in the past month and QTc interval change. Methadone dose was not associated with QTc change. DISCUSSION AND CONCLUSIONS An increase of mean QTc interval was found among methadone maintenance patients at six-month follow up. Electrocardiogram monitoring should be performed among patients who are at risk of frequently using amphetamines during methadone maintenance treatment.