Toru Hori

National Center of Neurology and Psychiatry, Кодаиры, Tōkyō, Japan

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Publications (12)38.15 Total impact

  • Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 04/2011; 31(2):95-6.
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    ABSTRACT: To develop and validate the Alcohol Relapse Risk Scale (ARRS) for Japanese alcohol-dependent individuals and to compare the features of relapse risk for alcohol-dependent individuals with those for stimulant abusers. The ARRS is a multidimensional self-rating scale consisting of 32 items based on the Stimulant Relapse Risk Scale (SRRS). Two hundred eighteen inpatients and outpatients with a history of alcohol dependence (181 males and 36 females) were recruited, provided informed consent, and were administered the ARRS. The Visual Analog Scale (VAS) for alcohol craving, current state of drinking, and data on relapse within 1 month after the rating were used for validation. Exploratory factor analysis highlighted five factors: stimulus-induced vulnerability (SV), emotionality problems (EP), compulsivity for alcohol (CA), lack of negative expectancy for alcohol (NE), and positive expectancy for alcohol (PE). Cronbach's alpha coefficient for each of the subscales ranged from .55 to .90 and was .90 for the total ARRS, indicating their adequate internal consistency. SV, EP, CA, PE, and total ARRS were significantly correlated with the VAS and current drinking state, supporting their concurrent validity. SV and total ARRS were significantly correlated with relapse, suggesting that the ARRS is useful for predicting relapse risk in alcohol-dependent individuals, similar to the SRRS for stimulant abusers. Compared with stimulant abusers, alcohol-dependent individuals tended to express their desires related to relapse more honestly on the scales. The ARRS has multidimensional psychometric properties that are useful for assessing the various aspects of alcohol relapse risk.
    Drug and alcohol dependence 04/2009; 101(1-2):20-6. DOI:10.1016/j.drugalcdep.2008.10.021 · 3.42 Impact Factor
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    ABSTRACT: Abnormal intracellular signaling molecules in dopamine signal transduction are thought to be associated with the pathophysiology of methamphetamine (METH)-use disorder. A recent study reported that a new intracellular protein, prostate apoptosis response 4 (Par-4), plays a critical role in dopamine 2 receptor signaling. We therefore analyzed the association between the Par-4 gene (PAWR) and METH-use disorder in a Japanese population (191 patients with METH-use disorder and 466 healthy controls). Using the recommended "gene-based" association analysis, we selected five tagging SNPs in PAWR from the HapMap database. No significant allele/genotype-wise or haplotype-wise association was found between PAWR and METH-use disorder. These results suggest that PAWR does not play a major role in METH-use disorders in the Japanese population.
    Annals of the New York Academy of Sciences 11/2008; 1139(1):83-8. DOI:10.1196/annals.1432.024 · 4.38 Impact Factor
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    ABSTRACT: A recent study showed a significant association between schizophrenia in European samples and the glutamate cysteine ligase modifier (GCLM) subunit gene, which is the key glutathione (GSH)-synthesizing enzyme. Since the symptoms of methamphetamine (METH)-induced psychosis are similar to those of schizophrenia, the GCLM gene is thought to be a good candidate gene for METH-use disorder or related disorders. To evaluate the association between the GCLM gene and METH-use disorder and schizophrenia, we conducted a case-control study of Japanese subjects (METH-use disorder, 185 cases; schizophrenia, 742 cases; and controls, 819). Four SNPs (2 SNPs from an original report and JSNP database, and 2 "tagging SNPs" from HapMap database) in the GCLM gene were examined in this association analysis; one SNP showed an association with both METH-use disorder and METH-induced psychosis. After Bonferroni's correction for multiple testing, however, this significance disappeared. No significant association was found with schizophrenia. Our findings suggest that a common genetic variation in the GCLM gene might not contribute to the risk of METH-use disorder and schizophrenia in the Japanese population.
    Annals of the New York Academy of Sciences 11/2008; 1139(1):63-9. DOI:10.1196/annals.1432.022 · 4.38 Impact Factor
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    ABSTRACT: The mesolimbic system is thought to be involved in the reinforcing action of many addictive drugs and the release of dopamine modulated by neuronal nicotine cholinergic receptors (nAChRs). Several investigations suggested that nAChRs on dopaminergic terminals play an important role in the development of some long-lasting adaptations associated with drug abuse. A majority of high-affinity nicotine binding sites in the brain have been showed in heteropentameric alpha4 (alpha4) and beta2 subunit (beta2) of nAChRs. Therefore, we conducted a genetic association analysis of the alpha4 gene (CHRNA4) and beta2 gene (CHRNB2) with methamphetamine (METH)-use disorder (191 cases and 753 controls). We first evaluated the linkage disequilibrium (LD) structure of these genes and selected 7 and 5 tagging SNPs (tag SNPs) on CHRNA4 and CHRNB2, respectively. Some tag SNPs were significantly associated with total METH-use disorder and METH-induced psychosis; however, these associations were no longer statistically significant after Bonferroni's correction for multiple testing. In conclusion, our results suggest that neither CHRNA4 nor CHRNB2 plays a major role in Japanese METH-use disorder.
    Annals of the New York Academy of Sciences 11/2008; 1139(1):70-82. DOI:10.1196/annals.1432.023 · 4.38 Impact Factor
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    ABSTRACT: Because methamphetamine (METH) is metabolized by CYP2D6 at the first step of hydroxylation and demethylation, it is possible that functional variants of CYP2D6 alter susceptibility to methamphetamine-induced dependence. We genotyped CYP2D6*1, *4, *5, *10, and *14 for 202 patients with METH dependence and 337 controls in a Japanese population and found a significant association of the CYP2D6 gene with METH dependence (p=0.0299). The patients had fewer *10 and *14 alleles, which are hypofunction alleles, than the controls. CYP2D6 genotypes were divided into three phenotypes: extensive metabolizers, intermediate metabolizers, and poor metabolizers. There was no poor metabolizer among our Japanese subjects, and intermediate metabolizers of CYP2D6 were significantly fewer in methamphetamine-dependent subjects than in controls (p=0.0212), with an odds ratio of 0.62 (95% confidence interval: 0.51-0.76). The present study demonstrated that reduced CYP2D6 activity was a negative risk factor for methamphetamine dependence.
    Neuroscience Letters 04/2008; 434(1):88-92. DOI:10.1016/j.neulet.2008.01.033 · 2.03 Impact Factor
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    ABSTRACT: The dysbindin (DTNBP1 [dystrobrevin-binding protein 1]) gene has repeatedly been shown to be associated with schizophrenia across diverse populations. One study also showed that risk haplotypes were shared with a bipolar disorder subgroup with psychotic episodes, but not with all cases. DTNBP1 may confer susceptibility to psychotic symptoms in various psychiatric disorders besides schizophrenia. Methamphetamine psychosis, the psychotic symptoms of which are close to those observed in schizophrenia, was investigated through a case (n = 197)-control (n = 243) association analyses of DTNBP1. DTNBP1 showed significant associations with methamphetamine psychosis at polymorphisms of P1635 (rs3213207, p = .00003) and SNPA (rs2619538, p = .049) and the three-locus haplotype of P1655 (rs2619539)-P1635-SNPA (permutation p = .0005). The C-A-A haplotype, which was identical to the protective haplotype previously reported for schizophrenia and psychotic bipolar disorders, was a protective factor (p = .0013, odds ratio [OR] = .62, 95% confidence interval [CI] .51-.77) for methamphetamine psychosis. The C-G-T haplotype was a risk for methamphetamine psychosis (p = .0012, OR = 14.9, 95% CI 3.5-64.2). Our genetic evidence suggests that DTNBP1 is involved in psychotic liability not only for schizophrenia but also for other psychotic disorders, including substance-induced psychosis.
    Biological psychiatry 02/2008; 63(2):191-6. DOI:10.1016/j.biopsych.2007.03.019 · 10.26 Impact Factor
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    ABSTRACT: Glycine transporter (GlyT)-1 plays a pivotal role in maintaining the glycine level at the glutamatergic synapse. Glycine is an allosteric agonist of N-methyl-D-aspartate (NMDA) receptors. Because activation of NMDA receptors is an essential step for induction of methamphetamine dependence and psychosis, differences in the functioning of GlyT-1 due to genetic variants of the GlyT-1 gene (GLYT1) may influence susceptibility. A case-control genetic association study of the GLYT1 gene examined 204 patients with methamphetamine-use disorder and 210 healthy controls. We examined three single nucleotide polymorphisms (SNPs), SNP1, IVS3 + 411C > T, rs2486001; SNP2, 1056G > A, rs2248829; and SNP3, IVS11 + 22G > A, rs2248632, of the GLYT1 gene and found that SNP1 showed a significant association in both genotype (P = 0.0086) and allele (P = 0.0019) with methamphetamine-use disorder. The T-G haplotype at SNP1 and SNP2 was a significant risk factor for the disorder (P = 0.000039, odds ratio: 2.04). The present findings indicate that genetic variation of the GLYT1 gene may contribute to individual vulnerability to methamphetamine dependence and psychosis.
    American Journal of Medical Genetics Part B Neuropsychiatric Genetics 01/2008; 147B(1):54-8. DOI:10.1002/ajmg.b.30565 · 3.42 Impact Factor
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    ABSTRACT: To develop and validate a multidimensional measure of relapse risk for stimulants in Japanese drug abusers. A Stimulant Relapse Risk Scale (SRRS) was developed based on the Marijuana Craving Questionnaire and a discussion among three psychiatrists. We created 48 items after confirming the items including a variety of relapse risk, such as craving (expectancy, compulsivity, etc.) and emotionality problems. One hundred inpatients and outpatients with a history of stimulant abuse (71 males and 29 females) were recruited with informed consent, and were administered the SRRS. The Visual Analogue Scale for drug craving (VAS), Addiction Severity Index for Japanese (ASI-J), and data on relapse within 3 and 6 months after the rating were used for the validation. Exploratory factor analysis highlighted five factors: anxiety and intention to use drug (AI), emotionality problems (EP), compulsivity for drug use (CD), positive expectancies and lack of control over drug (PL), and lack of negative expectancy for drug use (NE). These accounted for 48.3% of the total variance. Thirty of the 43 items were classified into the five subscales. Cronbach's alpha coefficient for each subscale ranged from .55 to .82, and was .86 for the total SRRS, indicating their adequate internal consistency. AI, CD, PL, and total SRRS were significantly correlated with the drug-use composite score of the ASI-J, supporting their concurrent validity. AI, PL, NE, and total SRRS were significantly correlated with relapse, implying their predictive validity. The SRRS has multidimensional psychometric properties useful for assessing the various aspects of stimulant relapse risk.
    Drug and Alcohol Dependence 06/2007; 88(2-3):174-81. DOI:10.1016/j.drugalcdep.2006.10.005 · 3.42 Impact Factor
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    ABSTRACT: The Addiction Severity Index (ASI) is a frequently used clinical and research instrument that collects data from substance abusers in seven problem areas: medical, employment, alcohol, drug use, legal, family-social functioning, and psychiatric status. In each area, the ASI provides a composite score and severity rating that estimate the seriousness of the problem and the client's need for treatment. In the present study, we investigated the reliability and validity of the Japanese version of the ASI (ASI-J). One hundred and eleven subjects with a history of drug abuse were interviewed with a test battery including the ASI with informed consent. This revealed that: (a) the problem areas were independent of each other, underscoring the need for multidimensional assessment, (b) the inter-rater correlation of severity ratings in each area ranged from 0.68 to 0.99, and Cronbach's alpha coefficient for the items used for the composite score in each area ranged from 0.57 to 0.86, indicating their reliability with the exception of the drug and employment areas, and (c) several composite scores were significantly correlated with the drug craving levels assessed by a visual analogue scale, the abstinence period, mental health, and/or relapse, supporting their concurrent and predictive validity. These results suggest that the ASI-J has acceptable reliability and validity.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 09/2006; 41(4):368-79.
  • International Clinical Psychopharmacology 07/2006; 21(4):A31-A32. DOI:10.1097/00004850-200607000-00094 · 2.46 Impact Factor
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    ABSTRACT: We have introduced cognitive behavior therapy (CBT) into the treatment of substance dependence patients, which involves disease education and focused group therapy to obtain insight into the taking behavior and to establish concrete countermeasures to prevent relapse. We have created a bio-cognitive model based on biological aspects to explain the pathology of substance dependence. 'Dependence' is a term in behavioral pharmacology defined as reinforced drug seeking and taking behavior. Changes in taking behavior are thought to occur due to the repetition of the reinforcement action of psychoactive substances in the reward system of the brain. Therefore, when intake desire is strong, it is hard for patients to control themselves, and there is a feature of difficulties considering the process of thinking in CBT. In other words, when craving becomes strong, a chain of behavior happens spontaneously, without schema, involving automatic thoughts. We think that the improvement of protracted withdrawal syndrome (PWS) and entire frontal lobe function are important in learning to discern distortion of cognition. When PWS is improved, a conflict is easy to bring about in the process of drug seeking and taking behavior. And, it is easy to execute avoidance plans (coping skills) which are established to cope with craving in advance. We think that a goal for treatment is to discern drug seeking and taking behavior with natural emotion. The recovery of PWS and frontal lobe dysfunction takes a long time with a serious dependence, so we must perform repetition of CBT. As the treatment introduction of involuntary admission cases is adequate or cases of 1 to 3 months of admission treatment based on voluntary admission are hard to treat, treatment to obtain insights into patients while carrying out repeated CBT using a bio-cognitive model and to improve PWS could be a possibility as one treatment for the pathology of diversified substance dependence.
    Seishin shinkeigaku zasshi = Psychiatria et neurologia Japonica 02/2005; 107(11):1147-58.