Mian-Yoon Chong

Glycine transporter I inhibitor, N-Methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia

BACKGROUND Hypofunction of N-methyl-D-aspartate glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine or glycine, endogenous full agonists of the glycine site of N-methyl-D-aspartate receptor, or D-cycloserine, a partial agonist, improve the symptoms of schizophrenia. N-methylglycine (sarcosine) is an endogenous antagonist of glycine transporter-1, which potentiates glycines action on N-methyl-D-aspartate glycine site and can have beneficial effects on schizophrenia. METHODS Thirty-eight schizophrenic patients were enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/d), which was added to their stable antipsychotic regimens. Twenty of them received risperidone. Measures of clinical efficacy and side effects were determined every other week. RESULTS Patient who received sarcosine treatment revealed significant improvements in their positive, negative, cognitive, and general psychiatric symptoms. Similar therapeutic effects were observed when only risperidone-treated patients were analyzed. Sarcosine was well-tolerated, and no significant side effect was noted. CONCLUSIONS Sarcosine treatment can benefit schizophrenic patients treated by antipsychotics including risperidone. The significant improvement with the sarcosine further supports the hypothesis of N-methyl-D-aspartate receptor hypofunction in schizophrenia. Glycine transporter-1 is a novel target for the pharmacotherapy to enhance N-methyl-D-aspartate function.

Posttraumatic Stress Disorder Among Adolescent Earthquake Victims in Taiwan

OBJECTIVE To assess the exposure experience and prevalence of posttraumatic stress disorder (PTSD) among adolescent victims in the worst-affected region (Chungliao) near the epicenter of a severe earthquake (7.3 on the Richter scale) that occurred on September 21, 1999, in Taiwan. METHOD The experience of exposure to the earthquake and subjective symptoms of junior high school students aged 12 to 14 who remained in the area were assessed with self-rated questionnaires. Psychiatrists made independent diagnoses for PTSD by using the Childrens Interview for Psychiatric Syndromes. RESULTS Six weeks after the earthquake, 21.7% of 323 students demonstrated PTSD. Those with PTSD showed significantly more psychiatric symptoms than did those without PTSD. Being physically injured and experiencing the death of a close family member with whom they had lived were the 2 major risk factors for PTSD. CONCLUSIONS This study demonstrates that PTSD among adolescent victims of a severe earthquake in Taiwan is not as high as that reported in other studies. Methodological differences in the investigations are discussed, along with differences in symptom manifestations. However, long-term follow-up of these victims is recommended to prevent the development of other psychiatric complications.

Antipsychotic drug prescription for schizophrenia in East Asia: rationale for change

Abstract  The purpose of this international collaborative study was to investigate the prescription patterns of antipsychotic drugs for schizophrenia in East Asia and to analyze factors that affect these patterns. Prescription patterns for patients admitted for treatment of schizophrenia were surveyed using a standardized protocol from six East‐Asian region/countries: China, Hong Kong, Japan, Korea, Singapore and Taiwan. Patients’ social and clinical characteristics, psychiatric symptoms, course of illness, and adverse effects of medications were systematically assessed and recorded. Prescriptions of the first‐ and second‐generation antipsychotic drugs were compared. A total of 2399 patients were recruited. The second‐generation drugs comprised 28.1% of all prescribed antipsychotics, and 46% of the antipsychotic prescriptions were in the context of polypharmacy. The mean dosage of antipsychotics for the whole sample was 675.3 + 645.1 mg chlorpromazine equivalents. Japan had a high frequency of prescribing high doses and polypharmacy; Singapore had a high utilization of depot injections while China had a higher prescription of clozapine. Using multiple logistic regression analysis, distinctions in the prescription patterns of antipsychotic drugs were found: first‐generation drugs were mainly for controlling aggressive behavior, while second‐generation drugs were targeted at the alleviation of positive, negative psychotic symptoms as well as disruptive behavior in schizophrenia. The present collaborative study highlighted differences in the prescription patterns, especially the under‐utilization of second‐generation antipsychotic drugs in East Asia. The pattern of antipsychotic medication use varied from country to country and is likely to be influenced by the prevailing health‐care system, the availability and cost of the drugs.

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.).

Monoamine oxidase A gene polymorphism and suicide: An association study and meta-analysis

BACKGROUND Abnormalities in brain monoamine transmission have been implicated in the pathogenesis of suicidal behavior. Studies examining the association between monoamine oxidase A (MAOA)-uVNTR polymorphism and suicide revealed inconsistent findings. This study aims to evaluate the possible association between the MAOA-uVNTR polymorphism and suicidal behaviors by examining our own subjects and conducting a meta-analytic review. METHODS 373 unrelated psychiatric patients (including 160 suicide attempters and 213 non-suicide attempters) were genotyped for the MAOA-uVNTR polymorphism. A meta-analysis was then performed by pooling data from seven case-control association studies by random effects model. RESULTS Our results indicate that there is no association between the MAOA-uVNTR polymorphism and suicide attempts in both genders. It also reveals that there is no association with violent suicide attempts. In the meta-analysis, there is no association between the polymorphism and suicidal behaviors. Also, there is no difference in the allelic distribution between psychiatric patients with and without suicidal behaviors. Limitations Our study was constrained by the insufficient information about environmental risk factors of suicide. CONCLUSIONS Our study is the first one to use meta-analysis in exploring the role of the MAOA-uVNTR polymorphism in suicidal behavior in psychiatric patients. No significant association was found in our study, suggesting MAOA-uVNTR polymorphism is unlikely to contribute significantly to suicide behavior. Further studies investigating the gene-environment interaction or focusing on the genetic risk factors of endophenotypes of suicidal behaviors are warranted.

Depression in Chinese elderly populations

There is a scarcity of systematic reports on the prevalence of depression in Chinese elderly populations. The available reports used a variety of diagnostic and screening instruments to identify elderly depression. Furthermore, samples were drawn from different elderly populations. In spite of these difficulties, the reports are consistent in terms of the prevalence rates of severe depression which is lower than those reported in Western studies; though the prevalence rates of depressive symptoms approach those of most Western countries. However, the Chinese elderly showed a particular sensitivity to social factors either as vulnerability or protection factors for depression. There is a consistent social dimension in depressive complaints by Chinese elderly; hence the need to construct specific culturally sensitive instruments and to establish within ethnic group norms and diagnostic criteria for elderly depression. Current intervention efforts to prevent and ameliorate depression in the community‐dwelling elderly will be discussed.

High‐dose antipsychotic use in schizophrenia: a comparison between the 2001 and 2004 Research on East Asia Psychotropic Prescription (REAP) studies

AIMS We aimed to examine the frequency of high-dose (defined as mean chlorpromazine mg equivalent doses above 1000) antipsychotic prescriptions in schizophrenia and their clinical correlates in the context of a comparison between studies in 2001 and 2004 within six East Asian countries and territories. METHODS Prescriptions of high-dose antipsychotic for a sample of 2136 patients with schizophrenia from six countries and territories (mainland China, Hong Kong, Korea, Japan, Taiwan and Singapore) were evaluated in 2004 and compared with data obtained for 2399 patients in 2001. RESULTS Overall, the comparison between 2001 and 2004 showed a significant decrease in high-dose antipsychotic use from 17.9 to 6.5% [odds ratio (OR) 0.32, 95% confidence interval (CI) 0.26, 0.39, P < 0.001]. Patients who received high-dose antipsychotics were significantly more likely to have multiple admissions (OR 1.96, 95% CI 1.16, 3.33, P = 0.009), more positive psychotic symptoms such as delusions (OR 2.05, 95% CI 1.38, 3.05, P < 0.001) and hallucinations (OR 1.85, 95% CI 1.30, 2.64, P = 0.001), but less likely to have negative symptoms (OR 0.58, 95% CI 0.40, 0.82, P = 0.002). Multivariate regression analyses revealed that prescription of high-dose antipsychotics was also predicted by younger age (P < 0.001), time period of study (2001; P < 0.001), use of first-generation antipsychotic (P < 0.001) and depot antipsychotics (P < 0.001) as well as antipsychotic polytherapy (P < 0.001). CONCLUSIONS We identified the clinical profile and treatment characteristics of patients who are at risk of receiving high antipsychotic doses. These findings should provide impetus for clinicians to constantly monitor the drug regimes and to foster rational, evidence-based prescribing practices.

Correlates of methamphetamine use for Taiwanese adolescents.

Abstract  The aim of the present study was to assess the associations between methamphetamine (MAP) use and psychiatric comorbidity, individual attitudes and personal knowledge of MAP use, family characteristics and peer factors in Taiwanese adolescents via a case–control study. Two hundred adolescent MAP users and 400 adolescent non‐users were recruited. Their psychiatric comorbidity, attitudes and knowledge toward MAP use, family characteristics and peer interactions were assessed systematically. The associations between MAP use and those factors were examined by univariate and multivariate analysis. In conditional logistic regression analysis, comorbid conduct disorder, attitude favorable to MAP use and poor knowledge of MAP use, disrupted parenting, lower caregiver education level, having friends using or providing MAP and actively interacting with peers were associated significantly with MAP use. Adolescent MAP use was correlated with multiple factors that lie within individuals and the interaction with their family and peers. Correlates of MAP use identified in the present study may be helpful for the design and implementation of preventive intervention.

Adjunctive benzodiazepine treatment of hospitalized schizophrenia patients in Asia from 2001 to 2008

Benzodiazepines are commonly prescribed to patients with schizophrenia in many countries, but as little is known about such treatment in Asia, we evaluated their adjunctive use for 6761 in-patients diagnosed with schizophrenia in nine Asian countries using a cross-sectional study design in 2001, 2004 and 2008. Multivariate logistic regression and multivariate linear regression analyses were performed to assess predictors of benzodiazepine use and dose, respectively. Overall, 54% of the patients received adjunctive benzodiazepines at an average daily dose equivalent to 30.3 mg diazepam, with minor changes over the years sampled. Benzodiazepine use was highest in Taiwan and Japan, lowest in Thailand and China, and was associated with fewer years ill, presence of delusions (OR 1.24), hallucinations (OR 1.22), disorganized speech (OR 1.17), social or occupational dysfunction (OR 1.16), and use of mood stabilizers (OR 3.15), antiparkinsonian (OR 1.79) or antidepressant drugs (OR 1.33), and lower doses of antipsychotics (all p=0.016 to <0.001). Benzodiazepine doses were highest in Taiwan and China, lowest in Korea and Singapore; higher doses were associated with being young, male, physically aggressive, receiving mood stabilizers, and having electroconvulsive treatment (all p=0.019 to <0.001). Benzodiazepine use was associated with neurological and systemic adverse effects. In conclusion, benzodiazepine use was common in Asian patients with schizophrenia. Predictors of benzodiazepine use and dose differed in this population. Critical clinical guidelines should be developed specifically for Asian countries to address sound practices in regard to use of benzodiazepines for psychotic disorders.