Kazuhiko Iwahashi

Azabu University, Sagamihara, Kanagawa, Japan

Are you Kazuhiko Iwahashi?

Claim your profile

Publications (123)218.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Recent genome-wide analysis has indicated that the autism susceptibility candidate 2 (AUTS2) gene is involved in the regulation of alcohol consumption. We hypothesised that AUTS2 might be associated with the development of alcohol dependence. Therefore, in this exploratory study, we compared the genotype and allele frequencies of the polymorphisms rs6943555 and rs9886351 in the AUTS2 gene between patients with alcohol dependence and healthy control subjects living in a Japanese provincial prefecture. We also examined whether or not the haplotypes consisting of these polymorphisms are related to alcohol dependence. Methods: The subjects of this study consisted of 64 patients with alcohol dependence and 75 unrelated healthy people. The AUTS2 genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Results: No significant differences in the genotype and allele frequencies of the polymorphisms AUTS2 rs6943555 and rs9886351 were found between alcohol dependence and control subjects. On the other hand, the frequencies of the AUTS2 haplotypes were significantly different between them, and the rs6943555 and rs9886351 A-A haplotype was associated with alcohol dependence (p=0.0187). Conclusion: This suggests that the rs6943555 and rs9886351 A-A haplotype might affect the vulnerability to alcohol dependence pathogenesis. Further studies are needed to confirm the reproducibility of the results of this study with increased numbers of subjects.
    No preview · Article · Jan 2016 · Acta Neuropsychiatrica
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Norepinephrine is an important chemical messenger that is involved in mood and stress in humans, and is reabsorbed by the norepinephrine transporter (NET). According to Cloninger's theory, the noradrenergic system mediates the personality trait of reward dependence. Thus far, although association studies on NET gene polymorphisms and Cloninger's personality traits have been reported, they yielded inconsistent results. Therefore, in the present study we investigated whether or not the 1287G/A, -182T/C and -3081A/T polymorphisms of the NET gene (SLC6A2) are associated with reward dependence-related traits, as assessed by the five-factor model. After written informed consent was obtained from participants, the three NET gene polymorphisms were analyzed by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and personality was assessed by the Neuroticism Extraversion Openness-Five Factor Inventory (NEO-FFI) in 270 Japanese university students. A significant relation was found between the -3081A/T functional promoter polymorphism and NEO-FFI scores: those with the T allele exhibited a lower extraversion (E) score than those without the T allele (Mann-Whitney U-test: z=-3.861, p<0.001). However, there was no correlation between the other NET gene polymorphisms and E score, and no association with other dimensions and these three polymorphisms. We conclude that the -3081A/T functional polymorphism in the NET gene may affect the extraversion of reward dependence-related traits, as measured by NEO-FFI. However, we used only the shortened version of NEO-PI-R in this study. Further investigations are necessary using the full version of self-rating personality questionnaires.
    Full-text · Article · Jul 2015 · Psychiatry investigation
  • [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia and bipolar disorder show high comorbidity with smoking dependence. Several previous studies reported that glycogen synthase kinase 3β (GSK3β), which is widely expressed in the brain including the dopamine projection areas such as the amygdala, nucleus accumbens and hippocampus, may play a role in neuropsychiatric disorders and dopamine- and serotonin-mediated behavior. In this study, we have analyzed the association of three single nucleotide polymorphisms (SNPs) within GSK3β gene (rs3755557, rs334558, rs6438552) with the smoking habits and age at smoking initiation in a sample of 384 young adult Japanese, which included 172 smokers and 212 non-smokers. As a result, rs334558 was significantly associated with smoking habits in genotype frequency and allelic frequency (P < 0.05). Furthermore, higher haplotype 3 (T-T-T) and haplotype 5 (A-T-C) frequencies were observed in non-smokers than smokers (P < 0.05). Three functional polymorphisms examined in this study reportedly increase transcriptional activity when they have a high-activation allele such as the A allele of -1727A/T (rs3755557), the T allele of -50T/C (rs334558) or T allele of -157T/C (rs6438552). Thus, it was suggested in this study that changes in GSK3β activity may have an impact on smoking habits.
    No preview · Article · Jun 2015 · Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Several studies have suggested that the norepinephrine transporter (NET) may play an important role in the pathogenesis of alcohol dependence. Therefore, in this study, we investigated whether the NET gene polymorphism is a susceptibility factor for alcohol dependence in 64 alcoholics and 73 healthy controls. In addition, we examined whether the combination of the NET and serotonin transporter genotypes are associated with alcohol dependence. The NET (1287G/A, -182T/C, and -3081A/T) and serotonin transporter (5-HTT3'UTR) genotypes were determined by the polymerase chain reaction (PCR)--restriction fragment length polymorphism (RFLP) method. No significant differences in genotype and allele frequencies of the NET and serotonin transporter gene polymorphisms were found between alcoholics and controls. The haplotype frequencies of the NET gene polymorphisms were not also significantly different between them. Furthermore, the combination of the NET and serotonin transporter genotypes had not significant effects on alcohol dependence. The present study suggests that the polymorphisms of 1287G/A, -182T/C and -3081A/T in NET gene are not.risk factors in alcohol dependence.
    No preview · Article · Dec 2014 · Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
  • Source
    [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 r2 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.
    Full-text · Article · Jul 2014 · Clinical Neuropharmacology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Feb 2014 · Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Dec 2013 · Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Nov 2013 · Japanese Journal of Neuropsychopharmacology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Aug 2013 · Japanese Journal of Neuropsychopharmacology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Aug 2012 · Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Jun 2012 · Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Apr 2012 · International Journal of Psychiatry in Clinical Practice
  • Eiji Yoshihara · Jun Aoki · Kouhei Kurihara · Maki Numajiri · Kazuhiko Iwahashi
    [Show abstract] [Hide abstract]
    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.
    No preview · Article · Dec 2011 · Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Dec 2010 · Rinsho byori. The Japanese journal of clinical pathology
  • Jun Aoki · Kazuhiko Iwahashi · Jun Ishigooka · Kazutaka Ikeda

    No preview · Article · Nov 2010 · Psychiatry Research
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Oct 2010 · Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Jul 2010 · Neuroscience Letters
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Jun 2010 · Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology
  • [Show abstract] [Hide abstract]
    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.
    No preview · Article · Mar 2010 · Journal of Clinical Neuroscience
  • Yuya Onozawa · Eiji Yoshihara · Jun Aoki · Kazuhiko Iwahashi
    [Show abstract] [Hide abstract]
    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.
    No preview · Article · Dec 2009 · Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence

Publication Stats

1k Citations
218.13 Total Impact Points

Institutions

  • 1998-2015
    • Azabu University
      • • Laboratory of Physiology
      • • Graduate School of Environmental Health
      Sagamihara, Kanagawa, Japan
  • 1990-2002
    • Kagawa University
      • • Faculty of Medicine
      • • Department of Psychiatry and Neuology
      • • Department of Biochemistry
      Takamatsu-shi, Kagawa-ken, Japan
  • 1997
    • The University of Tokushima
      • Faculty of Integrated Arts and Sciences
      Tokusima, Tokushima, Japan