K Iwahashi

Azabu University, Sagamihara, Kanagawa-ken, Japan

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Publications (112)209.64 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The GSK-3β gene, GSK3B, codes for an enzyme that is a target for the action of mood stabilizers, lithium and possibly valproic acid.In this study, the relationship between haplotypes consisting of single nucleotide polymorphisms (SNPs) of GSK3B -50T/C and -1727A/T and the effect of lithium was studied among Japanese bipolar disorder lithium nonresponders and responders.The distributions of the GSK3B haplotypes (-50T/C and -1727A/T) showed a trend for significant difference between the lithium nonresponders and responders (global P=0.07074). Haplotype 1 (T-A) was associated with a higher lithium response (haplotype-specific P=0.03477), whereas haplotype 2 (C-A) was associated with a lower lithium response (haplotype-specific P=0.03443).The pairwise D' and r values between the 2 SNPs in this study were 1.0 and 0.097, respectively. The 2 SNPs showed weak linkage disequilibrium with each other.
    Clinical neuropharmacology. 07/2014;
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    ABSTRACT: To facilitate elucidation of the pathogenesis of alcohol dependence, we investigated the relationship between a genetic variant of diazepam biding inhibitor (DBI) C/A polymorphism (rs2276596) and alcohol dependence. We determined the DBI genotypes using a novel method involving PCR-RFLP in healthy controls and alcoholics with a diagnosis of alcohol dependence by ICD-10 (F10.20). There was a significant difference in the rs2276596 polymorphism C/A allele frequency of the DBI gene (P < 0.0001) between alcoholics and healthy controls. The present data suggested that a mutant allele of the DBI was one of the risk factors for alcohol dependence as for the rs2276596 polymorphism.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 02/2014; 49(1):39-44.
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    ABSTRACT: As a help of the mechanism elucidation of alcoholism, we studied the relationship between brain-derived neurotrophic factor (BDNF) rs6265, 270 C/T (ID number has not yet been determined), and rs10835210 gene polymorphisms, which are reported to be related to bipolar disorder, and alcoholics. We genotyped the three polymorphisms in the BDNF gene using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) in 65 alcoholics and 71 healthy controls. In this study, there was no significant difference in the frequency of rs6265 and 270 C/T polymorphisms between alcoholics and controls (P > 0.05). However, there was a significant difference in the genotype frequency of rs10835210 polymorphism between alcoholics and controls (P < 0.05), in which the CA heterozygote genotype and A allele frequency was higher in alcoholics than in the controls. It suggests the possibility that the BDNF rs10835210 gene polymorphism affects the etiology of alcoholism.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 12/2013; 48(6):407-14.
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    ABSTRACT: In this study, the relationship between the haplotypes consisting of single nucleotide polymorphisms (SNPs) of serotonin 2A receptor (5HT2AR) gene (HTR2A) 102T/C (rs6313) and -1438A/G (rs6311) and smoking behavior was studied among 101 smokers and 99 non-smokers. It was shown that the genotypic and allelic frequencies of these polymorphisms were not associated with the smoking behavior. However, according to haplotype analysis, higher haplotype 1 ((-1438G) G-(102)T) frequency was observed in smokers than in non-smokers (P < 0.05). Pairwise D' and gamma2 values between the two SNPs in this study were 0.916 and 0.805, respectively. The two SNPs thus showed strong linkage disequilibrium with each other. This study suggests that 5-HT2AR gene haplotype (G-T) may be related to smoking behavior.
    11/2013; 33(5-6):237-40.
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    ABSTRACT: In this study, the relationship between the haplotypes consisting of single nucleotide polymorphisms (SNPs) of GSK-3beta -50T/C and -1727A/T and the derivation of smoking was studied among 102 smokers and 103 non-smokers. It was shown that the GSK-3beta -50T/C polymorphism may be linked with the smoking. There is significantly lower T-allele frequency in the smokers than non-smokers (chi2 (2) = 21.01, P = 0.000027; chi2 (1) 13.28, P = 0.00026). According to haplotype analysis, there was an association between smokers and non-smokers (global P = 0.00029). Higher haplotype 1 (T-A) frequency was observed in non-smokers than in smokers (P = 0.00036), whereas higher haplotype 2 (C-A) frequency was observed in smokers than in non-smokers (P = 0.000053). Pairwise D' and r2 values between the two SNPs in this study were 0.51 and 0.042, respectively. The two SNPs showed weak linkage disequilibrium with each other. This study suggests that GSK-3beta -50T/C polymorphism and two haplotypes may be related to smoking behavior.
    08/2013; 33(4):175-8.
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    ABSTRACT: The relationship between the polymorphisms (SNPs) of the beta-adrenergic receptor (beta-AR) gene and personality assessed by TCI (Temperament and Character Inventory), was studied among 192 healthy Japanese subjects (121 male subjects and 71 female subjects). In this study, the statistical analyses were performed overall and separately for each sex. As a result, it was shown that there were significant relationships between SD (self-directedness) and 49Ser/Gly (rs1801252) in ADRB1, P (persistence) and 389Arg/Gly (rs1801253) in ADRB1, and ST (self-transcendence) and 27Gln/Glu (rs1042714) in ADRB2 overall. Among the male subjects, there were further significant relationships between ST and 49Ser/Gly in ADRB1, NS (novelty-seeking), HA (harm avoidance) and P and 389Arg/Gly in ADRB1, and P and 64Arg/Trp(rsrs4994) in ADRB3. Among the female subjects, there were also significant relationships between SD and 49Ser/Gly in ADRB1, and C (cooperativeness) and 389Arg/Gly in ADRB1. Thus it was shown that there were correlations between beta-AR gene polymorphisms and several subscales of TCI.
    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 08/2012; 32(4):227-31.
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    ABSTRACT: GSK-3beta codes for an enzyme which is a target for the action of mood stabilizers, lithium and possibly of valproic acid. The relationship between the polymorphisms (SNPs) of GSK-3beta-50T/C and -1727A/T and the effect of lithium was studied among 29 Japanese bipolar patients. It was shown that GSK-3beta-50T/C may be linked with the effect of lithium treatment. There is a significantly higher T-allele frequency in the lithium responders than non-responders (df = 1, chi2 = 6.971, 0.01 > P > 0.001; Yates' continuity correction). However, there is not a significant relationship between the polymorphisms of GSK-3beta-1727A/T and the effect of lithium treatment.
    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 06/2012; 32(3):161-3.
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    ABSTRACT: Previous studies have shown the possibility that animal-assisted therapy (AAT) is useful for promoting the recovery of a patient's psychological, social, and physiological aspect. As a pilot study, we measured the effect that AAT had on cerebral activity using near-infrared spectroscopy (NIRS), and examined whether or not NIRS be used to evaluate the effect of AAT biologically and objectively. Two patients with mood [affective] disorders and a healthy subject participated in this study. We performed two AAT and the verbal fluency task (VFT). The NIRS signal during AAT showed great [oxy-Hb] increases in most of the prefrontal cortex (PFC) in the two patients. When the NIRS pattern during AAT was compared with that during VFT, greater or lesser differences were observed between them in all subjects. The present study suggested that AAT possibly causes biological and physiological changes in the PFC, and that AAT is useful for inducing the activity of the PFC in patients with depression who have generally been said to exhibit low cerebral activity in the PFC. In addition, the possibility was also suggested that the effect of AAT can be evaluated using NIRS physiologically and objectively.
    International Journal of Psychiatry in Clinical Practice 04/2012; 16(3):205-13. · 1.31 Impact Factor
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    ABSTRACT: As a help of the mechanism elucidation of alcoholism, we studied the relationship between glycogen synthase kinase 3-beta (GSK3B) -50T/C and -1727A/T polymorphisms, which are reported to relate to bipolar disorder. We genotyped the two polymorphisms in GSK3B gene using a polymerase chain reaction (PCR) in 71 health controls and 47 alcoholics. In this study, there was no significant difference in the frequency of GSK3B -50T/C and -1727A/T polymorphisms between alcoholics and controls. We suggested that there was no significant association of GSK3B -50T/C and -1727A/T polymorphisms with alcoholism.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 12/2011; 46(6):570-5.
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    ABSTRACT: There is no particular electroencephalographic activity known to be associated with consciousness disturbance in uremic patients; however, a slow wave activity is generally observed during consciousness disturbance. Abnormal electroencephalographic activity was observed in 30 (67%) of 45 chronic renal failure patients during chronic hemodialysis without consciousness disturbance, and slow wave activity was observed in 58%. The frequency of the electroencephalographic background activity correlated with blood urea nitrogen (BUN) and serum Ca levels, but not with K, IP, and creatinine levels. Electroencephalographic activity can be estimated with reference to BUN or serum Ca levels in the blood of uremic patients.
    Rinsho byori. The Japanese journal of clinical pathology 12/2010; 58(12):1169-75.
  • Jun Aoki, Kazuhiko Iwahashi, Jun Ishigooka, Kazutaka Ikeda
    Psychiatry Research 11/2010; 187(1-2):312-3. · 2.68 Impact Factor
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    ABSTRACT: As a help of the relationship between bipolar disorder and alcoholism, we studied the relationship between GSK-3 beta -50T/C polymorphism, which is reported to the relationship for bipolar disorder, and Japanese alcoholics. And we investigated the relationship between GSK-3 beta -50T/C polymorphism and DBI +529A/T polymorphisms, which is reported to one of the risk factor for alcoholism. We analyzed the GSK-3 beta genotype using a polymerase chain reaction (PCR), and DBI genotype using PCR with confronting two-pair novel primers (PCR-CTPP) in 75 health controls and 64 alcoholics. In this study, there was no significant difference in the frequency of GSK-3 beta -50T/C polymorphism between alcoholics and controls (p = 0.883), and there was no significant difference in the frequency of DBI +529A/T polymorphism (p = 0.131). Also, there was no relationship between GSK-3 beta -50T/C polymorphism and DBI +529A/T allele in alcoholism (p = 0.907). We suggested that bipolar disorder may not be one of the pathogenesis of alcoholism, and that there was no relationship between GSK-3 beta -50T/C polymorphism and DBI +529A/T polymorphism.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 10/2010; 45(5):430-6.
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    ABSTRACT: Although the serotonin (5-hydroxytryptamine (5-HT)) 2A receptor has been reported to be associated with pain, no relationship has been found between single nucleotide polymorphisms in the 5-HT2A receptor gene and analgesic requirements. To clarify the mechanism of individual differences in analgesic requirements, we investigated the relationship between the 5-HT2A 102T/C gene polymorphism and analgesic requirements in 135 patients who underwent major open abdominal surgery and were managed with continuous epidural analgesia with opioids after surgery. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. We found that the 102T/C polymorphism had significant main effects with regard to analgesic requirements. In addition, significant interaction effects were found between the 102T/C polymorphism and sex in terms of analgesic requirements. Among female subjects, patients with the T/T genotype of the 102T/C polymorphism had more analgesic requirements than those with the other genotypes. This finding suggests that the linkage disequilibrium block, which includes the 102T/C polymorphism of the 5-HT2A receptor gene, is involved in individual differences in analgesic requirements in women.
    Neuroscience Letters 07/2010; 479(1):40-3. · 2.03 Impact Factor
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    ABSTRACT: During daycare programs of animal assisted therapy (AAT), we collected data on the brain function of two affective disorder patients who received psychotropic drug therapy with fNIRS, after written informed consent was obtained. A male patient at first showed a bloodstream drop, seen in the lower inside part of frontal lobe. In both patients, at least a slight activation of the function of the frontal lobe was seen during the therapy. Therefore, an activation effect of AAT was seen at least objectively by fNIRS.
    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 06/2010; 30(3):129-34.
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    ABSTRACT: In 181 healthy Japanese volunteers we examined the relationship between personality, sensitivity to pain and a single nucleotide polymorphism (rs3813034) in the 3' untranslated region (3' UTR) of the serotonin transporter (5-HTT) gene (SLC6A4). Pain sensitivity was assessed by using cold and pressure thresholds. Personality was assessed by the Temperament and Character Inventory (TCI). Males without the T allele (G/G) showed a significantly higher spiritual acceptance (ST3) score than those who had the T allele (T/T and T/G). Females with the T allele (T/T and T/G) showed significantly higher transpersonal identification (ST2) and self-transcendence (ST) scores than those without the T allele (G/G). As for pain sensitivity and its relationship with TCI, we found a low negative correlation between cold water stimulation, disorderliness (NS4) and novelty seeking (NS) in males, whereas in females we found a low positive correlation between cold water stimulation, self-acceptance (SD4) and pure-hearted principles (C5), as well as pressure stimulation and SD4. It is possible that the 5-HTT 3' UTR gene polymorphism affects the character dimensions of Cloniger's theory, and that there might be a low correlation between pain and a part of the personality.
    Journal of Clinical Neuroscience 03/2010; 17(5):574-8. · 1.25 Impact Factor
  • Yuya Onozawa, Eiji Yoshihara, Jun Aoki, Kazuhiko Iwahashi
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    ABSTRACT: It has been reported that electroencephalographic (EEG) examinations of alcohol dependents reveal a few abnormal findings. However, we show abnormal findings in 47 (64%) of 73 alcohol dependents in whom disturbance of consciousness, convulsions, disturbance of memory, emotional disorders and hallucination were present. Our results indicate that EEG examination may be necessary for real time assessment of brain function in alcoholism.
    Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 12/2009; 44(6):659-69.
  • Kazuhiko Iwahashi, Jun Aoki
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    ABSTRACT: The nicotine metabolism of CYP2A6 (CYP2A6*1A,*1B, and *1C), and the cholecystokinin (CCK; which ­modulates the release of dopamine) and CCK-A receptor gene and personality traits for NEO-FFI, was ­investigated for the mechanism for elucidation of the smoking behavior in Japanese populations. The frequency of the CYP2A6*4C allele, which is a whole deleted allele of the human CYP2A6 gene, was higher, whereas that of CYP2A6*1A/*1B heterozygotes with higher nicotine metabolism activity was lower in nonsmokers than in smokers. There was also a significant difference between the current smoking and nonsmoking groups in the allele frequency of the CCK –45C/T polymorphism. It was also shown that the Openness (O) factor for smokers was significantly higher than that of nonsmokers; however, there were no significant differences in the Neuroticism (N), Extraversion (E), Agreeable (A), and Conscientiousness (C) scores among smokers than nonsmokers. It was suggested that the CYP2A6*4C allele may prevent the carrier from ­smoking, and being a CYP2A6*1A/*1B heterozygote and the CCK T allele may be risk factors for developing smoking behavior. Also, it is possible that persons with a low score in Openness may be refraining from smoking because they have a general negative impression toward smoking.
    Drug and Chemical Toxicology 10/2009; 32(4). · 1.29 Impact Factor
  • Jun Aoki, Kazutaka Ikeda, Kazuhiko Iwahashi
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    ABSTRACT: There are gene polymorphisms changing the expression or activation of the serotonin (5-HT) receptors, which are associated with pain. This review showed an availability of 5-HT2A receptor gene polymorphism in analgesic sensitivity. To search gene polymorphisms related to analgesic sensitivity is important to further effective pain management. In future 5-HT2A receptor gene polymorphisms, together with polymorphisms of other genes, may greatly contribute to effective postoperative pain management and personalized medicine.
    Masui. The Japanese journal of anesthesiology 09/2009; 58(9):1130-5.
  • Australian and New Zealand Journal of Psychiatry 08/2009; 34(4). · 3.29 Impact Factor
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    ABSTRACT: We investigated the relationship between the genetic polymorphism (s/l) of 5-HT2A receptors (A-1438G) and 5-HTT (s/l), and the drug effects among 31 patients who are administering olanzapine, as a help of the tailor made medical care in a time. As for the genetic polymorphism of 5-HT2AR, G/G group showed a significantly improvement tendency in the PANSS positive syndrome score in comparison with the group which did not have a G gene (AA and AG). It may be possible that this finding help to predict the drugs effect of olanzapine on the patients with excite state, who are used many antipsychotics together out of necessity.
    Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 08/2009; 29(4):141-4.

Publication Stats

748 Citations
209.64 Total Impact Points

Institutions

  • 1999–2011
    • Azabu University
      • • Laboratory of Physiology
      • • Graduate School of Environmental Health
      Sagamihara, Kanagawa-ken, Japan
  • 2003–2006
    • Hamamatsu University School of Medicine
      • Research Center for Child Mental Development
      Hamamatsu, Shizuoka-ken, Japan
  • 1996–2002
    • Kagawa University
      • • Faculty of Medicine
      • • Department of Forensic Medicine
      • • Department of Psychiatry and Neuology
      Takamatsu-shi, Kagawa-ken, Japan
  • 1997–2000
    • Hokkaido University
      • Institute of Immunological Science
      Sapporo-shi, Hokkaido, Japan
    • The University of Tokushima
      • Faculty of Integrated Arts and Sciences
      Tokusima, Tokushima, Japan