2006 Fiscal Year Final Research Report Summary
Methamphetamine Causes Reactive Microgliosis in the Brains of Human Abusers
| Project/Area Number |
17591204
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
SEKINE Yoshimoto Hamamatsu Univ Sch of Med, Psychiatry and Neurology, Assistant Professor, 医学部, 助手 (70324358)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEI Noriyoshi Hamamatsu Univ Sch of Med, Psychiatry and Neurology, Associate Professor, 医学部, 助教授 (80206937)
MINABE Yoshio Hamamatsu Univ Sch of Med, Hamamatsu Univ Hospital, Psychiatry and Neurology, Lecturer, 医学部附属病院, 講師 (60181947)
NAKAMURA Kazuhiko Hamamatsu Univ Sch of Med, Hamamatsu Univ Hospital, Psychiatry and Neurology, Lecturer, 医学部附属病院, 講師 (80263911)
MORI Norio Hamamatsu Univ Sch of Med, Psychiatry and Neurology, Professor, 医学部, 教授 (00174376)
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| Project Period (FY) |
2005 – 2006
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| Keywords | addiction / methamphetamine / positron emission tomography / microglia / dopamine / ドパミン |
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| Research Abstract |
Methamphetamine (METH) is a popular addictive drug whose is associated with multiple neurological and psychiatric adverse events. The drug is also toxic to dopaminergic and serotonergic systems of the brain. Neuronal damage is associated with the increased expression of microglial cells that are thought to be involved in either pro-toxic or protective mechanisms in the brain. Although increased microgliosis has been observed in animal models of METH neurotoxicity, no study has reported on the status of microglial activation in human METH abusers. The present study reports on 12 abstinent METH abusers and 12 age-, gender-, education-matched control subjects who underwent positron emission tomography using a radiotracer for activated microglia, [^<11>C] (R)-(1-[2-chlorophenyl]-N-methyl-N-[1-methylpropyl]-3-isoquinoline carboxamide) ([^<11>C] (R)-PK11195). Compartment analysis was used to estimate quantitative levels of binding potentials (BPs) of [11C](R)-PK11195 in brain regions innervated by dopaminergic and/or serotonergic projections. The mean levels of [^<11>C](R)-PK11195 binding were higher in METH abusers than those in control subjects in all brain regions (over 250% higher, p < 0.01 for all). In addition, [11C](R)-PK11195 BP levels were inversely related to the duration of METH abstinence in the midbrain (p < 0.01), striatum (p < 0.01), orbitofrontal cortex (p < 0.05), and insular cortex (p < 0.05). These results suggest that chronic self-administration of METH can cause reactive microgliosis in the brains of human METH abusers, a level of activation that appears to subside over longer periods of abstinence. Thus, early intervention with anti-inflammatory drugs that block microglial activation might offer therapeutic benefits to METH abusers.
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[Journal Article] Possible association of beta-arrestin 2 gene with methamphetamine use disorder, but not schizophrenia.2007
Author(s)
Ikeda M., Ozaki N., Suzuki T., Kitajima T., Yamanouchi Y., Kinoshita Y., Kishi T., Sekine Y., Iyo M., Harano M., Komiyama T., Yamada M., Sora I., Ujike H., Inada T., Iwata N
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Genes. Brain. Behav. 6(1)
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Okada K., Hashimoto K., Iwata Y., Nakamura K., Tsujii M., Tsuchiya K.J., Sekine Y., Suda S., Suzuki K., Sugihara G., Matsuzaki H., Sugiyama T., Kawai M., Minabe Y., Takei N., Mori N
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Prog. Neuropsychopharmacol. Biol. Psychiatry 31(1)
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[Journal Article] Increased levels of serum soluble L-selectin in unmedicated patients with schizophrenia.2007
Author(s)
Iwata Y., Suzuki K., Nakamura K., Matsuzaki H., Sekine Y., Tsuchiya K.J., Sugihara G., Kawai M., Minabe Y., Takei N., Mori N
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Schizophr. Res. 89(1-3)
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[Journal Article] Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia.2007
Author(s)
Iwata Y., Nakajima M., Yamada K., Nakamura K., Sekine Y, Tsuchiya K.J., Sugihara G., Matsuzaki H., Suda S., Suzuki K., Takei N., Mori N., Iwayama Y., Takao H., Yoshikawa T., Riley B., Makoff A., Sham P., Chen R., Collier D
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Neurosci. Res. 57(2)
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[Journal Article] Decreased serum levels of hepatocyte growth factor in male adults with high-functioning autism.2007
Author(s)
Sugihara G., Hashimoto K., Iwata Y., Nakamura K., Tsujii M., Tsuchiya K.J., Sekine Y., Suzuki K., Suda S., Matsuzaki H., Kawai M., Minabe Y., Yagi A., Takei N., Sugiyama T., Mori N
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Prog. Neuropsychopharmacol. Biol. Psychiatry 31(2)
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[Journal Article] Genetic analyses of the brain-derived neurotrophic factor (BDNF) gene in autism.2007
Author(s)
Nishimura K., Nakamura K., Anitha A., Yamada K., Tsujii M., Iwayama Y, Hattori E., Toyota T., Takei N., Miyachi T., Iwata Y., Suzuki K., Matsuzaki H., Kawai M., Sekine Y., Tsuchiya K., Sugihara G., Suda S., Ouchi Y., Sugiyama T., Yoshikawa T., Mori N
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Journal Title
Biochem. Biophys. Res. Commun. 356(1)
Pages: 200-206
Description
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[Journal Article] Brain serotonin transporter density and aggression in abstinent methamphetamine abusers.2006
Author(s)
Sekine Y., Ouchi Y., Takei N., Yoshikawa E., Nakamura K., Futatsubashi M., Okada H., Minabe Y., Suzuki K., Iwata Y., Tsuchiya K.J., Tsukada H., Iyo M., Mori N
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Journal Title
Arch. Gen. Psychiatry 63(1)
Pages: 90-100
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[Journal Article] Perospirone is a new generation antipsychotic : evidence from a positron emission tomography study of serotonin 2 and D2 receptor occupancy in the living human brain.2006
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Sekine Y., Ouchi Y., Takei N., Yoshikawa E., Okada H., Minabe Y., Nakamura K., Suzuki K., Iwata Y., Tsuchiya K.J., Sugihara G., Mori N
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Journal Title
J. Clin. Psychopharmacol. 26(5)
Pages: 531-533
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[Journal Article] Positive association of AKT1 haplotype to Japanese methamphetamine use disorder.2006
Author(s)
Ikeda M., Iwata N., Suzuki T., Kitajima T., Yamanouchi Y., Kinoshiya Y., Sekine Y., Iyo M., Harano M., Komiyama T., Yamada M., Sora I., Ujike H., Inada T., Ozaki N
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Journal Title
Int. J. Neuropsychopharmacol. 9(1)
Pages: 77-81
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[Journal Article] A novel scale including strabismus and 'cuspidal ear' for distinguishing schizophrenia patients from controls using minor physical anomalies.2006
Author(s)
Yoshitsugu K., Yamada K., Toyota T., Aoki-Suzuki M., Minabe Y., Nakamura K., Sekine Y., Suzuki K., Takei N., Itokawa M., Mori N., Yoshikawa T
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Journal Title
Psychiatry Res. 145(2-3)
Pages: 249-258
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[Journal Article] Linkage disequilibrium and association with methamphetamine dependence/psychosis of μ-opioid receptor gene polymorphisms.2006
Author(s)
Ide S., Kobayashi H., Ujike H., Ozaki N., Sekine Y., Inada T., Harano M., Komiyama T., Yamada M., Iyo M., Iwata N., Tanaka K., Shen H., Iwahashi K., Itokawa M., Minami M., Satoh M., Ikeda K., Sora I
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Journal Title
Pharmacogenomics J. 6(3)
Pages: 179-188
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[Journal Article] An association study between catechol-O-methyl transferase gene polymorphism and methamphetamine psychotic disorder.2006
Author(s)
Suzuki A., Nakamura K., Sekine Y., Minabe Y., Takei N., Suzuki K., Iwata Y., Kawai M., Takebayashi K., Matsuzaki H., Iyo M., Ozaki N., Inada T., Iwata N., Harano M., Komiyama T., Yamada M., Sora I., Ujike H., Mori N
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Journal Title
Psychiatr. Genet. 16(4)
Pages: 133-138
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[Journal Article] Association analysis of □-opioid receptor gene polymorphisms in methamphetamine dependence/psychosis.2006
Author(s)
Kobayashi H., Hata H., Ujike H., Harano M., Inada T., Komiyama T., Yamada M., Sekine Y., Iwata N., Iyo M., Ozaki N., Itokawa M., Naka M., Ide S., Ikeda K., Numachi Y., Sora I
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Journal Title
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Pages: 482-486
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[Journal Article] Evidence that variation in the peripheral benzodiazepine receptor (PBR) gene influences susceptibility to panic disorder.2006
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Nakamura K., Yamada K., Iwayama Y., Toyota T., Furukawa A., Takimoto T., Terayama H., Iwahashi K., Takei N., Minabe Y, Sekine Y., Suzuki K., Iwata Y., Pillai A., Nakamoto Y., Ikeda K., Yoshii M., Fukunishi I., Yoshikawa T., Mori N
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Am. J. Med. Genet. B Neuropsychiatr. Genet. 141(3)
Pages: 222-226
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[Journal Article] Genetic variant of prodynorphin gene is risk factor for methamphetamine dependence.2006
Author(s)
Nomura A., Ujike H., Tanaka Y., Otani K., Morita Y., Kishimoto M., Morio A., Harano M., Inada T., Yamada M., Komiyama T., Sekine Y., Iwata N., Sora I., Iyo M., Ozaki N., Kuroda S
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Neurosci. Lett. 400(1-2)
Pages: 158-162
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[Journal Article] Association analysis of SOD2 variants with methamphetamine psychosis in Japanese and Taiwanese populations.2006
Author(s)
Nakamura K., Chen C.K., Sekine Y., Iwata Y., Anitha A., Loh el-W., Takei N., Suzuki A., Kawai M., Takebayashi K., Suzuki K., Minabe Y., Tsuchiya K., Yamada K., Iyo M., Ozaki N., Inada T., Iwata N., Harano M., Komiyama T., Yamada M., Sora I., Ujike H., Ball D.M., Yoshikawa T., Lin S.K., Mori N
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Journal Title
Hum. Genet. 120(2)
Pages: 243-252
Description
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[Journal Article] Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder.2006
Author(s)
Aoyama N., Takahashi N., Kitaichi K., Ishihara R., Saito S., Maeno N., Ji X., Takagi K., Sekine Y., Iyo M., Harano M., Komiyama T., Yamada M., Sora I., Ujike H., Iwata N., Inada T., Ozaki N
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Pages: 1644-1649
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[Journal Article] Association study of the dihydropyrimidinase-related protein 2 gene and methamphetamine psychosis.2006
Author(s)
Ujike H., Sakai A., Nakata K., Tanaka Y., Kodaka T., Okahisa Y., Harano M., Inada T., Yamada M., Komiyama T., Hori T., Sekine Y., Iwata N., Sora I., Iyo M., Ozaki N., Kuroda S
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Journal Title
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Pages: 90-96
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[Journal Article] Association study of the tumor necrosis factor-alpha gene and its 1A receptor gene with methamphetamine dependence.2006
Author(s)
Nomura A., Ujike H., Tanaka Y., Kishimoto M., Otani K., Morita Y., Morio A., Harano M., Inada T., Yamada M., Komiyama T., Hori T., Sekine Y., Iwata N., Sora I., Iyo M., Ozaki N., Kuroda S
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Journal Title
Ann. N. Y. Acad. Sci. 1074
Pages: 116-124
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[Journal Article] No association between CART (cocaine-and amphetamine-regulated transcript) gene and methamphetamine dependence.2006
Author(s)
Morio A., Ujike H., Nomura A., Tanaka Y., Morita Y., Otani K., Kishimoto M., Harano M., Inada T., Komiyama T., Yamada M., Sekine Y., Iwata N., Iyo M., Sora I., Ozaki N., Kuroda S
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Journal Title
Ann. N. Y. Acad. Sci. 1074
Pages: 411-417
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[Journal Article] Increased serum levels of glutamate in adult patients with autism.2006
Author(s)
Shinohe A., Hashimoto K., Nakamura K., Tsujii M., Iwata Y., Tsuchiya K.J., Sekine Y., Suda S., Suzuki K., Sugihara G., Matsuzaki H., Minabe Y, Sugiyama T., Kawai M., Iyo M., Takei N., Mori N
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Prog. Neuropsychopharmacol. Biol. Psychiatry 30(8)
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[Journal Article] Reduced serum levels of brain-derived neurotrophic factor in adult male patients with autism.
Author(s)
Hashimoto K., Iwata Y., Nakamura K., Tsujii M., Tsuchiya K.J., Sekine Y., Suzuki K., Minabe Y., Takei N., Iyo M., Mori N
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Journal Title
Prog Neuropsychopharmacol Biol. Psychiatry (in press)
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[Journal Article] Decreased Serum Levels of Epidermal Growth Factor in Adult Subjects with High-Functioning Autism.
Author(s)
Suzuki K., Hashimoto K., Iwata Y., Nakamura K., Tsujii M., Tsuchiya K.J., Sekine Y, Suda S., Sugihara G., Matsuzaki H., Sugiyama T., Kawai M., Minabe Y., Takei N., Mori N
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Journal Title
Biol. Psychiatry (in press)
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[Journal Article] Decreased serum levels of PECAM-1 in subjects with high-functioning autism : a negative correlation with head circumference at birth.
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[Journal Article] The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis.
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[Journal Article] Identification of functional polymorphisms in the promoter region of the human PICK1 gene and their association with methamphetamine psychosis.
Author(s)
Matsuzawa D., Hashimoto K., Miyatake R., Shirayama Y., Shimizu E., Maeda K., Suzuki Y., Mashimo Y., Sekine Y., Inada T., Ozaki N., Iwata N., Harano M., Komiyama T., Yamada M., Sora I., Ujike H., Hata A., Sawa A., Iyo M
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Journal Title
Am. J. Psychiatry (in press)
Description
「研究成果報告書概要(欧文)」より
