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Hsien-Yuan Lane

Publications and source records attributed to Hsien-Yuan Lane.

At least 19 recordsLinked to original sources
PubMed2006

Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia.

BACKGROUND: Agonists at the N-methyl-D-aspartate (NMDA)-glycine site (D-serine, glycine, D-alanine and D-cycloserine) and glycine transporter-1 (GlyT-1) inhibitor (N-methylglycine, or called sarcosine) both improve the symptoms of stable chronic schizophrenia patients receiving concurrent antipsychotics. Previous studies, however, found no advantage of D-serine, glycine, or D-cycloserine added to clozapine. The present study aims to determine the effects of sarcosine adjuvant therapy for schizophrenic patients receiving clozapine treatment. METHODS: Twenty schizophrenic inpatients enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/day) which was added to their stable doses of clozapine. Measures of clinical efficacy and side-effects were determined every other week. RESULTS: Sarcosine produced no greater improvement when co-administered with clozapine than placebo plus clozapine at weeks 2, 4, and 6. Sarcosine was well tolerated and no significant side-effect was noted. CONCLUSIONS: Unlike patients treated with other antipsychotics, patients who received clozapine treatment exhibit no improvement by adding sarcosine or agonists at the NMDA-glycine site. Clozapine possesses particular efficacy, possibly related to potentiation of NMDA-mediated neurotransmission. This may contribute to the clozapine's unique clinical efficacy and refractoriness to the addition of NMDA-enhancing agents.

Adult↗
PubMed2006

Risperidone-related weight gain: genetic and nongenetic predictors.

OBJECTIVE: A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously explore the effects of multiple candidate genes and environment factors on body weight of schizophrenia patients who received risperidone, a commonly used atypical antipsychotic agent. METHODS: One hundred twenty-three ethnically Han Chinese inpatients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days. Body weight and clinical manifestations were assessed biweekly. Drug efficacy was measured by the Positive and Negative Syndrome Scale (PANSS), and safety was evaluated by the Extrapyramidal Symptom Rating Scale (ESRS) and the UKU Side Effect Rating Scale. We collected body weight as the response value. Potential prognostic factors were baseline body weight, age, sex, diagnosis subtypes, risperidone dosage, PANSS total scores, treatment duration (weeks 0-6), and 15 genetic variants [across 10 candidate genes: 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, D1, D2, D3, and alpha1-adrenergic receptors, brain-derived neurotrophic factor (BDNF), and cytochrome P450 2D6 (CYP2D6)]. Because there were repeated assessments, multiple linear regression with the generalized estimating equation (GEE) method was used to adjust the within-subject dependence. RESULTS: Of 15 genetic polymorphisms examined, 5-HT2A 102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T significantly influenced body weight, and so did baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy. CONCLUSIONS: These results suggest that numerous genetic and nongenetic factors affect antipsychotics-related weight gain.

Adolescent↗
PubMed2006

Optimizing early prediction for antipsychotic response in schizophrenia.

OBJECTIVE: Researchers, by studying first-generation antipsychotics, have established an early prediction model, which had a favorable specificity but a low sensitivity. This study aims to optimize early prediction of treatment response for schizophrenia using a novel statistic method that can be done even under the Microsoft Excel system of a personal computer. METHODS: One hundred twenty-three inpatients with acutely exacerbated schizophrenia were given optimal therapy of risperidone, a commonly used second-generation antipsychotic agent. Response was defined as a reduction of 20% or more in the Positive and Negative Syndrome Scale total score. We applied the generalized estimating equation method's logistic regression to establish an early prediction model based on the treatment results of the first and the second weeks. RESULTS: The proposed method correctly predicted nonresponse at 4 and 6 weeks in 80.8% and 81.8% of the patients, respectively. The method also identified responder at 4 and 6 weeks in 80.0% and 82.8%, respectively. The predictive powers (or correct prediction rates) at 4 and 6 weeks were 80.3% and 82.4%, respectively. In addition, the results based on the responses in Positive and Negative Syndrome Scale scores were slightly better than those in Brief Psychiatric Rating Scale scores. CONCLUSIONS: Using the first 2 weeks' treatment results to predict the fourth or sixth week's treatment response is acceptable in terms of specificity, sensitivity, and predictive power. Further studies are needed. Moreover, whether this model could be applied to establish a prediction system for other psychotropics, such as antidepressants, also deserves research.

Adolescent↗
PubMed2006

Glutamate decarboxylase genes and alcoholism in Han Taiwanese men.

OBJECTIVE: Glutamate decarboxylase (GAD), the rate-limiting enzyme in the synthesis of gamma-aminobutyric acid (GABA), may be involved in the development of alcoholism. This study examined the possible roles of the genes that code for 2 forms of GAD (GAD1 and GAD2) in the development of alcoholism. METHOD: An association study was conducted among 140 male alcoholic subjects meeting the DSM-III-R criteria for alcohol dependence and 146 controls recruited from the Han Taiwanese in community and clinical settings. Psychiatric assessment of drinking conditions was conducted using a Chinese version of the Schedules for Clinical Assessment in Neuropsychiatry. The SHEsis and Haploview programs were used in statistical analyses. RESULTS: Nine single-nucleotide polymorphisms (SNPs) at the GAD1 gene were valid for further statistics. Between alcoholic subjects and controls, significant differences were found in genotype distributions of SNP1 (p=0.000), SNP2 (p=0.015), SNP4 (p=0.015), SNP5 (p=0.031), SNP6 (p=0.012), and SNP8 (p=0.004) and in allele distributions of SNP1 (p=0.001), SNP2 (p=0.009), and SNP8 (p=0.009). Permutation tests of SNP1, SNP2, and SNP8 demonstrated significant differences in allele frequencies but not in 2 major haplotype blocks. Three valid SNPs at the GAD2 gene demonstrated no associations with alcoholism. Further permutation tests in the only 1 haplotype block or individual SNPs demonstrated no significant differences. CONCLUSIONS: This is the first report indicating a possible significant role of the GAD1 gene in the development of alcohol dependence and/or the course of alcohol withdrawal and outcome of alcoholism.

Adult↗
PubMed2006

The study of electroacupuncture on cerebral blood flow in rats with and without cerebral ischemia.

Electroacupuncture (EA) is widely used to treat disorders of the nervous system, such as stroke. The aim of the present study was to investigate the effect of EA on cerebral blood flow (CBF) in cerebral ischemic rats. We developed an animal model of cerebral ischemia (CI) by occluding the blood flow of both common carotid arteries in Sprague-Dawley (SD) rats; 2 or 15 Hz EA was applied to both Zusanli acupoints. The levels of nitric oxide (NO) in the peripheral blood and amounts of calcitonin gene-related peptide (CGRP) in the cerebral cortex and thalamus were measured. In addition, L-N (G)-nitro arginine methyl ester (L-NAME) was used to measure the changes in CBF induced by EA in rats with and without CI. The results indicated that both 2 and 15 Hz EA increase the mean CBF in rats with and without CI. However, neither 2 nor 15 Hz EA induced changes in levels of NO in peripheral blood or changes in CGRP levels in cerebral cortex and thalamus. In addition, L-NAME did not change the increase in CBF. We concluded that both 2 and 15 Hz EA at both Zusanli acupoints induced the increase of CBF in rats with and without CI. Whether the effect of EA is related to NO or CGRP will be investigated in a future study.

Animals↗
PubMed2005

Expanded trinucleotide repeats in the TBP/SCA17 gene mapped to chromosome 6q27 are associated with schizophrenia.

Schizophrenia has a complex and non-Mendelian mode of inheritance. Recently, trinucleotide repeat (TNR)-containing genes have been considered as the candidate genes predisposing to schizophrenia. The purpose of this study was to determine whether a genetic association could be observed between schizophrenia and the TNR polymorphisms within the KLHL1AS/SCA8, PPP2R2B/SCA12, and TBP/SCA17 genes. We studied 100 unrelated schizophrenia patients and 124 controls without evident neurodegenerative or psychiatric disorders. The overall allele frequency distributions of the KLHL1AS/SCA8 and PPP2R2B/SCA12 genes were not significantly different between the schizophrenic patients and the control subjects (P>0.05). The allele frequency distribution in the schizophrenic patients was significantly different from that in the controls at the TBP/SCA17 gene (P=0.0149), with an increased frequency of 36 repeats in the patients and two patients carrying 45 TNR expansions were identified. TBP/SCA17 is the TATA box binding protein gene mapped to chromosome 6q27. The study suggests that TNR expansions of the TBP/SCA17 gene may contribute to the genetic risk of schizophrenia in rare cases.

Adult↗
PubMed2005

Sarcosine or D-serine add-on treatment for acute exacerbation of schizophrenia: a randomized, double-blind, placebo-controlled study.

CONTEXT: Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia. OBJECTIVE: To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Inpatient units of 2 major medical centers in Taiwan. Patients Sixty-five schizophrenic inpatients with acute exacerbation. INTERVENTIONS: Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy. MAIN OUTCOME MEASURES: Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores. RESULTS: The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P< or =.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P< or =.04 for all). D-serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains. CONCLUSIONS: This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed.

Acute Disease↗
PubMed2005

A functional polymorphism in the promoter region of the tryptophan hydroxylase gene is associated with alcohol dependence in one aboriginal group in Taiwan.

BACKGROUND: Polymorphisms within intron 7 of the tryptophan hydroxylase (TPH1) gene were found to be associated with alcohol dependence in different ethnic groups, including the aboriginal Bunun group in Taiwan. This study aimed to identify genetic variants at the TPH1 locus and to examine their associations with alcoholism. We hypothesized that the polymorphism of TPH1 gene is functional and influences the human circadian rhythm to contribute to the pathophysiology of alcohol dependence. METHODS: DNA from the Taiwanese Han and Bunun was subjected to sequence for screening genetic variation in the coding and promoter regions of the TPH1 locus. Polymorphisms among individuals with alcohol dependence and control subjects in two ethnic groups in Taiwan were investigated. RESULTS: Three variants in the TPH1 promoter region were identified, and the markers are in complete linkage disequilibrium in both populations. Positive associations at both allelic and genotypic levels were obtained between case and control groups in the Bunun. Expression studies demonstrated that the variants indeed affected reporter gene activity in human choriocarcinoma and colon adenocarcinoma cell lines. CONCLUSIONS: Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan. The associations between TPH1 genotypes and alcoholism may deserve further investigation.

Adult↗
PubMed2005

Dopamine D3 receptor Ser9Gly polymorphism and risperidone response.

Risperidone is an atypical antipsychotic agent with efficacy for both positive and negative symptoms of schizophrenia. Risperidone is a potent dopamine D3 antagonist and agonism at D3 sites induces behavioral suppression in rodents. We thus hypothesized that D3 antagonism may contribute to response to risperidone in negative symptoms. This study aimed to explore the influence of the Ser9Gly polymorphism of the dopamine D3 receptor (DRD3) gene on response to risperidone after controlling for nongenetic factors. One hundred twenty-three Han Chinese patients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days. Clinical manifestations were measured biweekly with Positive and Negative Syndrome Scale and Nurses' Observation Scale for Inpatients Evaluation (for assessment of social functioning). For adjusting the within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was used to analyze the effects of Ser9Gly polymorphism and other covariates on clinical performance. Compared with patients with the Gly9Gly genotype, those with either Ser9Ser or Ser9Gly had better performance on negative symptoms after control for other prognostic factors (P = 0.0002 and 0.0092, respectively). Patients with the Ser9Ser genotype had better social functioning than those with Gly9Gly (P = 0.0029). The Ser9Gly polymorphism, however, did not significantly affect positive symptoms. Male gender, fewer previous hospitalizations, and higher risperidone dose also predicted better treatment response. These data suggest that the DRD3 Ser9Gly polymorphism or, alternatively, another genetic variation that is in linkage disequilibrium, may influence response to risperidone in negative symptoms and social functioning.

Adult↗
PubMed2005

Pharmacogenetic studies of response to risperidone and other newer atypical antipsychotics.

Risperidone and other newer atypical antipsychotics are becoming the mainstay for schizophrenia treatment. Recent studies suggest that the 5-hydroxytryptamine receptor 2A (5-HT2A) gene (HTR2A) T102C and G-1438A polymorphisms may influence treatment response of risperidone or olanzapine for schizophrenia's negative symptoms (e.g., blunted affect and social withdrawal). In addition, the HTR6 T267C polymorphism has been linked to risperidone response for positive symptoms (delusions and hallucinations). The dopamine D2 receptor (DRD2) Ser311Cys polymorphism may also play a role in determining risperidone efficacy for positive, negative and cognitive symptoms, the DRD2 Ins-A2/Del-A1 diplotype may predict better risperidone response, and the DRD3 Ser311Cys variant may affect general treatment response of several atypical agents. Although investigators have started to explore genetic effects on cognitions of schizophrenia patients receiving antipsychotics, future larger sized pharmacogenetic studies on both psychotic symptoms and cognitive functions are warranted.

Antipsychotic Agents↗
PubMed2004

Effects of dopamine D2 receptor Ser311Cys polymorphism and clinical factors on risperidone efficacy for positive and negative symptoms and social function.

Risperidone is an atypical antipsychotic agent with efficacy for both positive and negative symptoms of schizophrenia. However, what makes an antipsychotic 'atypical' remains unclear. We recently found that the T102C polymorphism in the 5-HT2A receptor gene could affect risperidone's efficacy for negative symptoms. The present study investigated the effect of the Ser311Cys polymorphism in the dopamine D2 receptor (DRD2) gene on risperidone treatment response. A total of 123 Han Chinese patients with acutely exacerbated schizophrenia were given risperidone for up to 42 days. Clinical manifestations were measured bi-weekly with Positive and Negative Syndrome Scale (PANSS) and Nurses' Observation Scale for Inpatients Evaluation (NOSIE, for assessment of social function). For adjusting the within-subject dependence over repeated assessments, multiple linear regression with generalized estimating equation methods was utilized to analyse the effects of Ser311Cys polymorphism and other covariates on clinical performance. Compared with patients who had the Ser311Ser genotype, patients with the Ser311Cys genotype had lower scores on PANSS Positive, Negative, General Psychopathology and Cognitive subscales and NOSIE, after adjustment for 5-HT2A T102C polymorphisms and other confounders. The 5-HT2A T102C polymorphism had marginal influences on PANSS Total and Negative subscale scores. Male gender, fewer previous hospitalizations, and higher risperidone dose predicted better treatment response after control for other variables. The preliminary results suggest that variations in the DRD2 gene influence risperidone treatment response for positive, negative, and cognitive symptoms, general psychopathology, and social functioning. Several clinical factors may also contribute to inter-individual differences in risperidone treatment response.

Adult↗
PubMed2004

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 glycine's 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.

Adult↗
PubMed2004

Risperidone response and 5-HT6 receptor gene variance: genetic association analysis with adjustment for nongenetic confounders.

Previous genetic-response studies, usually without considering environmental factors, encountered great difficulties in replication of results. Although atypical antipsychotics are becoming the mainstay for schizophrenia treatment which makes an antipsychotic "atypical" remains unclear. Risperidone (a widely used atypical antipsychotic agent) and several other atypicals have high affinities for 5-HT6 and 5-HT7 receptors. This study investigated the effects of the T-->C 267 polymorphism in the 5HT6 receptor gene and two rare Pro279Leu and Thr92Lys substitutions in the 5HT7 receptor gene on risperidone efficacy after rigorous control for nongenetic confounders. We found an association between the T-->C 267 polymorphism of the 5HT6 receptor gene and response to risperidone in 123 acutely ill schizophrenia inpatients after adjustment for confounders. Compared to patients with the T/C 267 genotype, those with T/T 267 showed less severe positive symptoms (p=0.006) and general psychopathology (including anxiety, depression, and cognitive dysfunctions) (p=0.005). The T-->C 267 polymorphism had no influences on negative symptoms. The two rare polymorphisms in the 5HT7 receptor gene were not observed in our sample. In conclusion, the 5HT6 receptor gene variant can affect risperidone response to positive symptoms and general psychopathology (but not negative symptoms) after control for nongenetic factors.

Acute Disease↗
PubMed2004

Dose-dependent alternations in the pharmacokinetics of olanzapine during coadministration of fluvoxamine in patients with schizophrenia.

Olanzapine, an atypical antipsychotic agent, is a substrate of the cytochrome P4501A2 (CYP1A2) enzyme. Administration of a potent CYP1A2 inhibitor (eg, fluvoxamine) may alter the pharmacokinetics of olanzapine. This study investigated the pharmacokinetic interactions between olanzapine and fluvoxamine in patients with schizophrenia. Ten male smokers were administrated a single dose of olanzapine 10 mg at baseline, followed by 2 weeks of fluvoxamine 50 mg/day and another 2 weeks of fluvoxamine 100 mg/day. Olanzapine 10 mg was given at day 10 during each fluvoxamine treatment. After pretreatment with fluvoxamine, the area under the curve, maximal plasma concentration, and half-time of olanzapine were significantly increased by 30% to 55%, 12% to 64%, and 25% to 32%, respectively. Volume of distribution and apparent clearance were significantly reduced by 4% to 26% and 26% t O 38%, respectively, after administration of fluvoxamine. Increases in area under the plasma concentration-time curve from time 0 to infinity appear to be dose dependent. Presumably, altered olanzapine pharmacokinetics are attributed to the inhibition of CYP1A2. Patients treated with the combination of olanzapine and fluvoxamine should be monitored carefully.

Adult↗
PubMed2004

Adjunctive fluvoxamine inhibits clozapine-related weight gain and metabolic disturbances.

BACKGROUND: Adjunctive fluvoxamine inhibits clozapine metabolism and decreases plasma norclozapine (a toxic metabolite of clozapine) to clozapine ratios. This study aimed to demonstrate the effects of fluvoxamine on clozapine-related weight gain, hyperglycemia, and lipid abnormalities. METHOD: Sixty-eight treatment-resistant inpatients with a DSM-IV diagnosis of schizophrenia were randomly assigned to 2 treatment groups for 12 weeks. The monotherapy group (N = 34) received clozapine (< or = 600 mg/day). The coadministration group (N = 34) received fluvoxamine (50 mg/day) plus low-dose clozapine (< or = 250 mg/day). The study was conducted from August 1999 to October 2002. RESULTS: The 2 groups were similar in demographic data; baseline body weight and body mass index (BMI); baseline serum glucose, triglyceride, and cholesterol levels; and steady-state plasma clozapine concentration. The monotherapy patients (but not the coadministration patients) had significantly higher (p < .05) body weight, BMI, and serum glucose and triglyceride levels after treatment than at baseline. At week 12, the monotherapy patients also had significantly higher glucose (p = .035), triglyceride (p = .041), and norclozapine (p = .009) (and numerically higher cholesterol) levels than the cotreatment patients. The changes in weight and serum glucose and triglyceride levels were significantly correlated (p = .026, p = .005, and p = .028, respectively) with the plasma concentration of norclozapine but not with plasma levels of clozapine. CONCLUSION: These results suggest that fluvoxamine cotreatment can attenuate weight gain and metabolic disturbances in clozapine-treated patients. Plasma levels of norclozapine, but not clozapine, are associated with increases in weight and serum glucose and triglyceride levels. Of note, coadministration of fluvoxamine could increase plasma clozapine levels markedly and carry the risk of adverse events. If this combined treatment is applied, conservative introduction with reduced clozapine dosage and careful therapeutic drug monitoring of clozapine concentration is recommended.

Adolescent↗