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Shih-Ku Lin

Publications and source records attributed to Shih-Ku Lin.

At least 19 recordsLinked to original sources
PubMed2006

Association analysis of SOD2 variants with methamphetamine psychosis in Japanese and Taiwanese populations.

SOD2 (superoxide dismutase 2) plays a crucial role in protecting the cells against damage caused by free radicals, by catalyzing their detoxification. On the other hand, cell damage caused by free radical generation following methamphetamine administration has been postulated as one of the possible pathophysiological mechanisms for methamphetamine psychosis. Hence, we investigated the association of SOD2 polymorphisms with the development of methamphetamine psychosis, in two independent populations of Japan and Taiwan. We recruited 116 patients with methamphetamine psychosis and 189 controls in Japan, and 135 patients with methamphetamine psychosis and 204 controls in Taiwan. The methamphetamine group was divided into two clinical subtypes: a transient type of psychosis (i.e., good prognosis) and a prolonged type of psychosis (i.e., poor prognosis), according to the course of the manifestation of psychosis. With reference to the genotypic and allelic frequencies of Ala/Val functional polymorphism in exon 2, we found significant differences between individuals with prolonged methamphetamine psychosis and control samples from Japan and Taiwan in the genotypic (P value 0.014 and 0.016, respectively) and in the allelic (P value 0.004 and 0.047, respectively) frequencies. Our results suggest that Ala/Val polymorphism of the SOD2 gene could be associated with the risk of developing methamphetamine psychosis.

Adolescent↗
PubMed2006

Higher plasma drug concentration in clozapine-treated schizophrenic patients with side effects of obsessive/compulsive symptoms.

Clozapine-induced obsessive/compulsive symptoms (OCS) have been reported by many authors. This study investigated the incidence of these side effects, together with the relation between these side effects and the plasma concentration (Cps) of clozapine and its metabolites norclozapine and clozapine-N-oxide in schizophrenic patients. One hundred and two schizophrenic patients treated with clozapine were interviewed and screened with questionnaires testing for OCS during a 1-year study period. Cps of clozapine and the metabolites were monitored using reversed-phase high-performance liquid chromatography with ultraviolet detection. Thirty-nine patients (38.2%) presented with OCS, and, of these, 29 patients (28.4%) were classified as clozapine-induced, with an average latent period of 39.8+/-22.5 months. The Cps of clozapine and norclozapine were significantly higher in patients with OCS than in those without (595.1+/-364.9 vs. 433.5+/-252.8 ng/mL, P=0.001 and 266.4+/-144.4 vs. 203.1+/-119.8 ng/mL) OCS. Clozapine-induced OCS were not uncommon side effects. The authors suggest that the emergence of these side effects may be related to higher Cps of clozapine and clinicians should routinely check for and manage these side effects.

Adult↗
PubMed2006

Association between dopamine receptor D1 A-48G polymorphism and methamphetamine abuse.

Several lines of evidence have suggested that substance abuse is mediated by the dopaminergic rewarding system, primarily through the activity of the dopamine receptor D1 (DRD1). The purpose of the present study was to evaluate the association of DRD1 A-48G polymorphism with methamphetamine (MAP) abusers and MAP-induced psychosis patients. A total of 363 MAP abusers and 425 healthy normal controls were enrolled. The structural Diagnostic Interview for Genetic Study was used to evaluate all MAP abusers. The MAP abusers were classified into psychosis (n = 135) and non-psychosis (n = 228) groups. A-48G polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism. The results show that male sex and a higher frequency of MAP abuse were the predisposing factors in the development of MAP psychosis. The DRD1 -48G allele frequency in the MAP psychosis group, non-psychosis group and the healthy normal controls was 0.14, 0.18 and 0.16, respectively. No association was found between DRD1 A-48G polymorphism and MAP abuse and MAP psychosis. However, the data provided additional evidence of ethnicity-related differences in the distribution of polymorphism in comparison to previous studies.

Adult↗
PubMed2006

Recidivism among male subjects incarcerated for illicit drug use in Taiwan.

Illicit drug users are generally considered both patients and criminals in Taiwan. This study presents drug use behaviors and criminal recidivism of male subjects incarcerated for illicit drug use in Taiwan after detoxification at a detention center. This study also examined the relationship between drug use behaviors and subsequent recidivism. Charts and crime records of 794 male patients from the acute detoxification unit in a detention center in northern Taiwan were reviewed. These subjects were incarcerated for methamphetamine or/and heroin use. The authors examined the relationship between the variables collected during detoxification and subsequent recidivism of illicit drug use in the following 5 years after detoxification. Of 794 subjects, 539 (67.9%) were repeat offenders during the following 5 years after detoxification. Their recidivism occurred primarily within the first 2 years after being released into the community. The recidivism rate for heroin users was significantly higher than that of methamphetamine users. Aged under 30 years, a previous criminal record, and a positive urine analyses test for illicit drugs upon entering the detoxification unit were significantly associated with recidivism. Recidivism rates of illicit drug users in Taiwan after detoxification in the detention center were substantially high. The efficacy of detoxification programs at detention centers in Taiwan needs to be re-evaluated.

Adult↗
PubMed2005

Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis.

It is not clear why some methamphetamine (MAMP) abusers develop psychotic symptoms, while others use MAMP regularly over long periods and remain unscathed. We tested the hypotheses that those users who develop MAMP-induced psychosis (MIP) have greater familial loading for psychotic disorders than users with no psychosis. Four hundred forty-five MAMP users were recruited from a psychiatric hospital and a detention center in Taipei, and were assessed with the Diagnostic Interview for genetic studies (DIGS-C) and the Family Interview for genetic study (FIGS-C). Morbid risk (MR) for psychiatric disorders in first-degree relatives was compared between those MAMP users with a lifetime diagnosis of MAMP psychosis and those without. The relatives of MAMP users with a lifetime diagnosis of MAMP psychosis had a significantly higher MR for schizophrenia (OR = 5.4, 95% CI: 2.0-14.7, P < 0.001) than the relatives of those probands who never became psychotic. Furthermore, the MR for schizophrenia in the relatives of the subjects with a prolonged MAMP psychosis (MIP-P) was higher than in the relatives of those users with a brief MAMP psychosis (MIP-B) (OR = 2.8, 95% CI: 1.0-8.0, P = 0.042). The greater his or her familial loading for schizophrenia, the more likely a MAMP user is to develop psychosis, and the longer that psychosis is likely to last.

Adult↗
PubMed2005

Ethnic variation in CYP2A6*7, CYP2A6*8 and CYP2A6*10 as assessed with a novel haplotyping method.

Cytochrome P450 2A6 is the main human nicotine metabolizing enzyme coded for by a highly polymorphic gene, CYP2A6. CYP2A6*7, CYP2A6*8 and CYP2A6*10 are variant alleles common to Asian ethnicities. The CYP2A6*7 and CYP2A6*8 alleles each contain a non-synonymous single nucleotide polymorphism (SNP) 6558T>C and 6600G>T, respectively, whereas the CYP2A6*10 haplotype allele contains both. We have developed the first haplotyping assay; it can unambiguously distinguish the CYP2A6*7, CYP2A6*8 and CYP2A6*10 alleles. The allele frequencies of these three variants were assessed using the novel haplotyping assay in Chinese-Canadian (n=112), Chinese-American (n=221), Taiwanese (n=319), Korean-American (n=207) and Japanese-Canadian (n=64) populations, as well as in Caucasian (n=110) and African-Canadian (n=113) populations. Our new method demonstrated higher frequencies of CYP2A6*7 and CYP2A6*10, and a lower frequency of CYP2A6*8 in Asian populations, but no significant change of allele frequencies in Caucasian or African-Canadian populations.

Africa↗
PubMed2004

Association analysis of the DRD4 and COMT genes in methamphetamine abuse.

We analyzed two polymorphisms in genes encoding proteins of the dopamine system, the Val158Met polymorphism in the catechol-O-methyltransferase gene and the 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene for association with methamphetamine abuse. We used a case/control design with 416 methamphetamine abusing subjects and 435 normal controls. All subjects were Han Chinese from Taiwan. We found an excess of the high activity Val158 allele in the methamphetamine abuser group, consistent with several previous reports of association of this allele with drug abuse. The 120-bp VNTR polymorphism in the promoter of the dopamine D4 receptor gene itself did not show significant association with methamphetamine abuse. However, analysis of the 120-bp VNTR polymorphism and the exon 3 VNTR in the dopamine D4 receptor as a haplotype showed significant association with methamphetamine abuse, which gave an empirical P value 0.0034 for a heterogeneity model. Moreover, there were significant interactive effects between polymorphisms in the catechol-O-methyltransferase and dopamine D4 genes. The evidence of interaction between COMT 158 Val/Met and DRD4 48-bp VNTR polymorphisms (P = 0.0003, OR = 1.45, 95% CI: 1.148-1.77), and between COMT 158 Val/Met and DRD4 120 bp promoter polymorphisms (P = 0.01, OR = 1.10, 95% CI: 1.10-1.18) were significant but the latter was weak. We conclude that genetic variation in the dopamine system may encode an additive effect on risk of becoming a methamphetamine abuser.

Adolescent↗
PubMed2004

Changing seroepidemiology of hepatitis B, C, and D virus infections in high-risk populations.

Needle-sharing and sexual contact are important transmission routes of hepatitis B, C, and D virus (HBV, HCV, HDV) infection. This study aimed to investigate the current status of these viral infections among high-risk populations including prostitutes and intravenous (i.v.) drug users, compared with the prevalence rate reported previously to examine the changing seroepidemiology. Of the 916 female prostitutes, 79 (9%) were positive for antibody to HCV (anti-HCV), 111 (12%) were positive for HBV surface antigen (HBsAg), and 5 (5%) had antibody to HDV (anti-HDV). The prevalence rate was significantly lower compared to that in 1989-1991 (12%, P = 0.037) for HCV infection, and to that in 1988 (59%) and 1996 (40%) (P < 0.0001) for HDV infection. Of the 494 i.v. drug users, 87 (18%) patients were HBsAg carriers and 12 (14%) were anti-HDV-positive. The prevalence rate of HDV infection was significantly lower than that reported in 1985 (79%, P < 0.0001). Among the 443 tested i.v. drug users, 182 (41%) were anti-HCV-positive, significantly lower than that in 1985 (53%, P = 0.026). Of the 263 male prostitutes, 11 (4%) were anti-HCV-positive, 45 (17%) were HBsAg-positive, and 7 (16%) were anti-HDV-positive. Of the 129 illegal immigrant prostitutes, 7 (5%) were anti-HCV-positive, 15 (12%) were HBsAg-positive and none were positive for anti-HDV. In conclusion, the findings indicate a declining prevalence of HCV and HDV infections among drug users and prostitutes over the past 16 years. Male prostitutes and immigrant prostitutes are new "high-risk" populations and may become a reservoir for disease transmission.

Adolescent↗
PubMed2004

DAT polymorphism and diverse clinical manifestations in methamphetamine abusers.

The clinical outcome for methamphetamine (MAP) abusers is variable. MAP exerts its biological activity through rapid conversion to amphetamine (AP) and MAP itself. The dopamine transporter (DAT) is the main modulator of MAP/AP-induced dopamine release and dopamine neurotoxicity, and is also the major regulator of dopamine level in the brain. We tested for an association between a DAT-gene polymorphism and clinical variations in MAP abusers. A total of 146 MAP abusers were enrolled in the study and classified into three clinically distinct groups: MAP dependence (n = 30), MAP psychosis (n = 88) and chronic MAP psychosis (n = 28). Patients with schizophrenia (n = 79) and healthy controls (n = 72) were also recruited for the study. The 40 base pair variable number tandem repeat polymorphism in the 3'-untranslated region of the DAT was the focus of the investigation. The subjects were all Chinese residents of Taiwan. The respective allelic frequencies for DAT repeats 11, 10 and 9 were 0.067, 0.833 and 0.083 for the MAP-dependence group, 0.006, 0.864 and 0.119 for the MAP psychosis group, 0.018, 0.893 and 0.089 for the chronic MAP psychosis group, 0.019, 0.911 and 0.07 for the schizophrenic controls, and 0.021, 0.889 and 0.083 for the healthy controls. No significant associations were demonstrated between this DAT polymorphism in genotype and allele frequency and the clinical outcome of MAP abusers. The biological relevance of the variable number tandem repeat polymorphism in the 3'-untranslated region of DAT in MAP abusers was not demonstrated in this study.

3' Untranslated Regions↗
PubMed2004

Association analysis of dopamine D2-like receptor genes and methamphetamine abuse.

OBJECTIVES: Substance use disorders are familial, and genetic factors explain a substantial degree of their familial aggregation. This study employs an association approach to examine the genetic underpinning of methamphetamine (MAMP) use and MAMP-induced psychosis. METHODS: A total of 416 MAMP abusers from a hospital and a detention center in Taipei were interviewed with the Diagnostic Interview for Genetic Study and the Family Interview for Genetic Study. Genetic polymorphisms of D2-like dopamine receptor genes, DRD2 TaqI A, DRD3 Ser-9-Gly, and DRD4 exon III variable number of tandem repeats, were compared between: (a) MAMP users as a whole and 435 normal controls, and (b) those 154 individuals with MAMP-induced psychosis and the 252 MAMP users with no psychosis. RESULTS: None of the three markers we studied were associated with predisposition to psychosis among the MAMP abusers. The MAMP abusers had a higher (P=0.011) prevalence of the seven-repeat allele of DRD4 than normal controls. CONCLUSIONS: Chance fluctuations in the frequency of rare alleles and ascertainment differences in the case and control samples cannot be ruled out. Therefore, further studies of the seven-repeat allele in MAMP abusers and controls should be performed before an association can be established.

Female↗
PubMed2004

Psychiatric comorbidity and gender differences of persons incarcerated for methamphetamine abuse in Taiwan.

Methamphetamine (MAP) abuse has been common in Taiwan for the past decade. The purpose of the present study was to investigate MAP abuse in Taiwan, with specific attention to psychiatric comorbidity and gender differences. A total of 325 MAP abuse subjects (180 male, 145 female) from a detention center in Taipei were assessed with the Diagnostic Interview for Genetic Studies. The following were studied: drug use behavior, treatment-seeking behavior, lifetime prevalence of mood disorders, MAP psychosis, alcohol use disorders, pathological gambling and antisocial personality. The MAP-abuse subjects in Taiwan had high psychiatric morbidity and low access to mental health services. There also exist certain differences in the prevalence of psychiatric illnesses and treatment-seeking behavior between male and female subjects. Compared with their male counterparts, more female subjects reported experience of mental disturbance and experience of psychiatric treatment. The female subjects more commonly reported suicidal behaviors than the male subjects.

Adolescent↗
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↗
PubMed2003

Genetic toxicity of methamphetamine in vitro and in human abusers.

Methamphetamine (METH) is a widely abused psychomotor stimulant. Although numerous studies have examined METH-induced neurotoxicity, its ability to produce genotoxic effects has not been evaluated. In this article, we report on the genotoxicity of METH in vitro and in human METH abusers. METH induced his(+) revertants in Salmonella typhimurium strains TA98 and TA100, and increased the frequency of hprt mutants, micronuclei, and sister chromatid exchange (SCE) in cultured Chinese hamster ovary K1 (CHO-K1) cells. These METH-induced genotoxic effects were eliminated if METH exposure was conducted in the presence of rat liver S9, indicating that the genotoxicity was caused by METH, and not by metabolites of METH. In addition, reactive oxygen species (ROS) scavengers inhibited the METH-induced micronuclei in CHO-K1 cells. Further investigation with 76 human long-term METH abusers and 98 unexposed controls demonstrated that total METH exposure correlated with micronucleus and SCE frequencies in cultured lymphocytes. The results of this study indicate that METH is a genotoxic agent and that ROS may play a role in METH-induced genotoxicity.

Adult↗
PubMed2003

Comparison of the prevalence of substance use and psychiatric disorders between government- and self-employed commercial drivers.

Five hundred and five city government-employed bus drivers (GED) and 506 self-employed drivers (SED) who were primarily taxi drivers attending annual health check-ups were studied. A two-step survey was applied. Data on basic demographics were collected, the 12-item Chinese Health Questionnaire (CHQ), Michigan Alcoholism Screening Test (MAST), Drug Abuse Screen Test (DAST) questionnaires were administered and urine drug screening for amphetamine and benzodiazepines was performed in all subjects. Subjects with MAST scores > or =3, DAST > or =5 from both groups and CHQ > or =4 for the GED group and CHQ > or =7 for the SED group were regarded as a high-risk group; and subjects with normal MAST, DAST and CHQ results serving as the comparison group were invited for further interview by psychiatric specialists using the Mini International Neuropsychiatric Interview. The mean CHQ scores were 0.94 +/- 1.53 for the GED group and 2.08 +/- 2.42 for the SED group. The mean MAST scores for the GED and SED groups were 0.23 +/- 0.58 and 0.38 +/- 1.12; and the mean DAST scores were 1.03 +/- 0.85 and 1.41 +/- 1.89, respectively. The positive rate for benzodiazepines in urine screening by enzyme immunoassay was 8.3% for the GED group, and 8.5% for the SED group. After specification using liquid chromatography, this rate reduced to 4.6% and 3.7%, respectively. Only one subject in the SED group tested positive for urine amphetamine. The SED group had a higher rate of neurotic problems, psychiatric diagnosis and a higher frequency of substance use than the GED group. These findings suggest that different work style of commercial drivers may contribute to this phenomenon. The rate of psychiatric diagnosis was significantly higher in the high-risk subjects from both groups. Questionnaires such as CHQ, DAST and MAST are useful tools to screen out subjects at high risk of psychiatric disorders during routine health checks in labor workers.

Adult↗