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M Toru

Publications and source records attributed to M Toru.

At least 37 records · Page 2Linked to original sources
PubMed2000

An association study between two missense variations of the benzodiazepine receptor (peripheral) gene and schizophrenia in a Japanese sample.

The benzodiazepine receptor (peripheral) (BZRP) mainly localized on glial cells plays a role in neurosteroid synthesis, and increases with glial proliferation. We have recently reported a significant decrease in the density of BZRP labeled by [3H] PK 11195 in the postmortem brain of chronic schizophrenics, suggesting that dysfunctions of the BZRP are involved in the pathophysiology of schizophrenia. We screened 11 patients with schizophrenia and 10 controls, which were used in a previous postmortem study, for their genomic sequences of the BZRP gene in order to find DNA sequence variations. One novel missense polymorphism (His162Arg) and another previously reported missense mutation (Ala147Thr) were detected. An association study of the identified variations was then performed in an extended Japanese sample of 304 schizophrenic patients and 369 controls. While there was an increased tendency in the frequency of the 162Arg allele of schizophrenics compared to that of the controls (p = 0.0603), no statistically significant association with schizophrenia was observed in the Ala147Thr allele (p = 0.1016). These results do not suggest that the two missense polymorphisms play a major role in the genetic predisposition of schizophrenia in the Japanese sample.

Adult↗
PubMed2000

Serotonin 5-HT2 receptors in schizophrenic patients studied by positron emission tomography.

Using positron emission tomography (PET) and [11C]N-methylspiperone (NMSP), we examined 5-HT2 receptors in the cortex of schizophrenic patients in whom we previously observed decreased prefrontal D1 receptor binding. The subjects were 10 neuroleptic-naive schizophrenic patients, 7 schizophrenic patients who were drug-free but had previously been treated with neuroleptics, and 12 normal controls. A non-significant trend towards decreased prefrontal [11C]NMSP binding was observed in the neuroleptic-treated patients, suggesting a possible effect of previous neuroleptic treatment on the alteration in cortical 5-HT2 function. However, the neuroleptic-naive patients showed no noticeable difference in cortical [11C]NMSP binding compared to controls. Our results do not rule out the role of 5-HT2 function as a crucial site of therapeutic activity of schizophrenia, but they do suggest that cortical 5-HT2 receptors might not be primarily involved in the pathophysiology of schizophrenia.

Adult↗
PubMed2000

Mutation and association analysis of the 5' region of the dopamine D3 receptor gene in schizophrenia patients: identification of the Ala38Thr polymorphism and suggested association between DRD3 haplotypes and schizophrenia.

Although the association between the Ser9Gly polymorphism of the dopamine D3 receptor gene (DRD3) and schizophrenia has been investigated by many research groups, it is not known whether the Ser9Gly polymorphism alone or a variation in linkage disequilibrium may effect susceptibility to schizophrenia. We searched the 5' region of the DRD3 gene and found three novel polymorphisms: -712G/C, -205A/G, and Ala38Thr. The Ala38Thr polymorphism is located in the first transmembrane region and is conserved in the monkey, mouse, and rat. Case-control comparisons in 153 Japanese schizophrenia patients and 122 Japanese controls did not suggest an association between Ala38Thr and schizophrenia. However, there was a marginally significant association between the Ser9 allele of the Ser9Gly polymorphisms and schizophrenia (P = 0.02). Furthermore, there was a highly significant association between haplotypes of the -712G/C, -205A/G, and Ser9Gly polymorphisms and schizophrenia (P = 0.0007, corrected P = 0.007). These positive findings were replicated in an additional 99 Japanese schizophrenia patients and 132 controls (P = 0.04 and 0.0004, respectively). The most allelic differences of the Ser9Gly polymorphism between patient and control groups arose from the chromosome carrying specific alleles of the other three polymorphisms. This study indicates unknown variant(s) in linkage disequilibrium with the DRD3 haplotypes associated with schizophrenia.

5' Untranslated Regions↗
PubMed2000

Amantadine-induced multiple spike waves on an electroencephalogram of a schizophrenic patient.

Although amantadine is relatively free of side effects compared with levodopa, the incidence and severity of unwanted effects, such as hallucinations, insomnia and dizziness, markedly increase when the daily dose exceeds 200 mg. A 63-year-old schizophrenic female developed the Pisa syndrome following neuroleptic medication. She was started on a regimen of amantadine, 200 mg per day, on September 4, and the electroencephalogram (EEG) on September 11 was within normal limits. The dosage was increased to 300 mg on September 18 because there was no improvement and no side effects. Two days later a generalised convulsion occurred and an EEG revealed frequent multiple spikes or sharp waves with slow waves. No epileptic seizure has been observed since the amantadine was discontinued. The EEG on September 27 was again within normal limits. To our knowledge, the EEG of a patient with convulsion induced by amantadine has not been described previously. The epileptic mechanisms of amantadine have not been elucidated; however, it may be related to a modulating role of dopamine in the central nervous system.

Amantadine↗
PubMed1999

An event-related potential study in schizophrenia using Japanese sentences.

To examine the neurophysiological and cognitive characteristics of language disorder in schizophrenia, the N400 component and late positive component (LPC) of event-related potentials (ERPs) were investigated in medicated schizophrenic patients and health comparison subjects. The subjects were required to indicate whether Japanese sentence completions were semantically congruous or incongruous. The ERPs for the range of 300-500 ms to the incongruous completions contained a more negative component (N400), followed by LPC, which was inversely more positive for the incongruous than congruous condition. The N400 effect and the mean amplitude of the LPC were reduced in the patients. The attenuated N400 effect in schizophrenics mainly originated from an enhanced negativity for the congruous completions, suggesting that the use of context is poor in schizophrenia.

Adult↗
PubMed1999

A genetic polymorphism in the promoter region of DRD4 associated with expression and schizophrenia.

The human dopamine D4 receptor gene (DRD4) is an important candidate gene for schizophrenia. We identified a novel -521C>T polymorphism in the 5'-promoter region of DRD4. A transient expression method revealed that the T allele of this polymorphism reduces the transcriptional efficiency by 40% compared with the C allele. This polymorphism is of interest because of reported elevation of D4-like sites and DRD4 mRNA in the postmortem schizophrenic brain. The C allele frequency was significantly higher in 252 Japanese schizophrenics (0.48) than in 269 Japanese controls (0.41) (p = 0. 02) [odds ratio = 1.35 (95% confidence interval 1.05 - 1.72)]. Although the association is weak and should be considered tentative until other studies replicate it, this polymorphism provides a tool with the potential to examine whether DRD4 is related to susceptibility to and neuroleptic response in schizophrenia.

Adult↗
PubMed1999

No association between C-45T polymorphism in the Sp1 binding site of the promoter region of the cholecystokinin gene and alcoholism.

The activity of dopamine-containing neurons in the ventral tegmental area and nucleus accumbens may play a role in alcoholism. Cholecystokinin (CCK) co-exists in a large proportion of A10 dopamine neurons to exert some effect on dopamine-induced behavior. Recently, a C-45T polymorphism was discovered in the Sp1 binding site in the CCK gene promoter region. We investigated an association between the polymorphism and alcoholism in 209 Japanese DSM-III-R alcoholics and 113 Japanese control subjects. The patients and the control subjects had similar allele and genotype frequencies: the T allele frequencies were 0.27 in the patients and 0.28 in the control subjects and the CC, CT, and the TT genotype frequencies 0.53, 0.39, and 0.08 in the alcoholics and 0.53, 0.37, and 0.10 in the control subjects. Frequencies of clinical characteristics of Feighner's criteria for the lifetime diagnosis of alcoholism were not significantly different among the patient groups divided by the genotype. These findings indicate that the polymorphism has no major effect on the etiology of alcoholism.

Adult↗
PubMed1999

The 5' region of the tryptophan hydroxylase gene: mutation search and association study with alcoholism.

A deficiency in the serotonergic system has been suggested as a negative reinforcer in alcoholism. Tryptophan hydroxylase (TPH) is critical in the fine-tuning of serotonergic neurotransmission. We observed a significantly high frequency of the A allele of the IVS7+218A>C polymorphism in intron 7 of the TPH gene in Japanese alcoholics with histories of drinking-related antisocial behaviors compared with that of Japanese controls (p = 0.006). However, this polymorphism is intronic, and a study of TPH mRNA did not detect aberrant splice products or polymorphic nucleotides linked to this polymorphism. Therefore, we screened for variations in the promoter and 5'-untranslated region of the gene. Three novel variants/polymorphisms, -1066G>A in the 5' flanking region, IVS1B+23(GTTTT)4-5 in intron 1B, and IVS1C+50T>C in intron 1C, were identified. The -1066G>A and IVS1C+50T>C polymorphisms were in modest linkage disequilibrium with the IVS7+218A>C polymorphism. However, no significant association was found between the three novel polymorphisms and alcoholism. Although our findings reiterate that TPH may play some role in the genetic predisposition to alcoholism, the mechanism remains unknown.

Adult↗
PubMed1999

Association study between high and low activity polymorphism of catechol-O-methyltransferase gene and alcoholism.

Catechol-O-methyltransferase (COMT) is a key modulator of dopaminergic and noradrenergic neurotransmission. There is a functional polymorphism of the COMT gene, Val108Met in the soluble form of the enzyme (Val158Met in the membrane-bound form). Involvement of the dopaminergic systems in alcoholism has been suggested in mice and humans. We examined associations between this polymorphism and alcoholism in 175 Japanese alcoholics and 354 age- and gender-matched Japanese controls. No significant difference in the allelic distributions in alcoholics and controls and no significant associations between antisocial behaviors in alcoholics and this polymorphism were observed. Therefore, the COMT gene is not likely to play a significant role in alcoholism.

Adult↗
PubMed1999

Association between drinking-related antisocial behavior and a polymorphism in the serotonin transporter gene in a Japanese population.

BACKGROUND: Involvement of the serotoninergic system (S/S) in alcoholism has been suggested in both mice and humans. Previous studies have suggested the S/S genotype of the serotonin transporter gene promoter polymorphism to be associated with severe alcohol dependence marked by severe withdrawal symptoms. It has also been associated with alcoholics who exhibit a dissocial personality disorder. METHODS: We examined the polymorphism in 166 Japanese alcoholics who experienced withdrawal seizure or delirium and 290 Japanese controls. RESULTS: The S/S genotype was not increased in the patients. Exploratory analyses showed significantly less frequent S allele and S/S genotype frequencies in the alcoholics with a history of drinking-related arrests than in the controls (p = 0.009 and p = 0.03, respectively), perhaps reflecting previously reported harm avoidance personality traits associated with S/S. Alcoholics with the L allele had a significantly earlier onset of alcohol dependence than those with the S/S genotype (p = 0.01). CONCLUSIONS: The present study failed to provide supportive evidence for an association of the S/S genotype with severe alcoholism marked by physical withdrawal symptoms or with antisocial behaviors among the Japanese. Although our data support involvement of the central serotoninergic system in some types of alcoholism, the potential association findings of this study emerged as only exploratory and, therefore, should be understood as tentative until replicated in other studies.

Adult↗
PubMed1998

Association between polymorphisms in the type 1 sigma receptor gene and schizophrenia.

Several antipsychotic agents such as haloperidol and rimcazole are known to bind to sigma receptors with high affinity, and evidence for a potential link between sigma receptors and the etiology of schizophrenia has been reported. The present study was conducted to systematically search for nucleotide variants of the type 1 sigma receptor gene in 48 schizophrenics. Two polymorphisms were found: GC-241-240TT in the 5' flanking region and Gln2Pro. These two polymorphisms were in nearly complete linkage disequilibrium with each other. The Pro2 variant of the Gln2Pro polymorphism changes the endoplasmic reticulum retention signal motif. These polymorphisms were examined in an extended sample of schizophrenics (n = 308) and controls (n = 433) and a significant association between the presence of the TT/Pro2 haplotype and schizophrenia was observed (odds ratio = 1.27, P = 0.04).

Adolescent↗
PubMed1998

An increase in [3H] CGS21680 binding in the striatum of postmortem brains of chronic schizophrenics.

We measured adenosine 2a receptors in basal ganglia of 13 schizophrenics and 10 controls, using [3H] CGS21680 as a ligand for the receptor binding assay. There was a significant increase in the specific [3H] CGS21680 binding in the putamen and caudate, but not in the globus pallidus of externa, of the schizophrenic patients, compared to those of controls. These results provide evidence suggesting that adenosine 2a receptors play a role in the pathophysiology of schizophrenia.

Adenosine↗
PubMed1998

Systematic search for variations in the tyrosine hydroxylase gene and their associations with schizophrenia, affective disorders, and alcoholism.

Tyrosine hydroxylase is the rate-limiting step in the biosynthesis of catecholamines. To find variants in the tyrosine hydroxylase (TH) gene that are associated with schizophrenia, mood disorders, or alcohol dependence, all of the exons, the exon-intron boundaries, and the 5' promoter region of the TH gene were systematically screened for variants by single-strand conformation polymorphism analysis followed by direct nucleotide sequencing. Source DNAs for sequencing were from 88 Japanese patients comprised of 17 schizophrenics, 21 with mood disorders, and 50 alcoholics. Two novel variants, T-229A and Val468Met, were identified. Case-control comparisons demonstrated that distribution of these two variants were similar in the controls and the three psychiatric groups. Distributions of the previously reported Val81Met polymorphism alleles and the intron 1 TCAT repeat polymorphism alleles were similar in the four subject groups. Our study indicates that the TH gene is not likely to play a major role in the genetic predisposition to schizophrenia, mood disorders, or alcohol dependence.

Adult↗
PubMed1998

Evidence supporting an association between the DRB1 gene and schizophrenia in Japanese.

The authors attempted a replication of earlier studies that detected an association of HLA-DR4 and DR1 with schizophrenia. Japanese patients with schizophrenia (n = 266, DSM-III-R criteria) and Japanese controls (n = 283) were genotyped for DR1 and DR4 alleles using a combination of group-specific polymerase chain reaction (PCR) amplification and PCR-restriction fragment length polymorphism. Significant positive association with HLA-DR1 [odds ratio (OR) = 1.87, corrected p = 0.04] and a negative association with HLA-DR4 (OR = 0.63, corrected p = 0.02) was noted. DR1 and DR4 were independently associated with schizophrenia. The association of the DR1-positive/DR4-negative genotype with schizophrenia was modest (OR = 2.60, 95% confidence intervals = 1.38-4.89, corrected p = 0.008). Thus, these findings support an association of the HLA DRB1 gene locus with schizophrenia in the Japanese population. Since both DR4 and DR1 are positively associated with rheumatoid arthritis, our findings are not simply consistent with the known negative association between schizophrenia and rheumatoid arthritis.

Female↗
PubMed1998

Antidepressantlike effects of chronic nicotine on learned helplessness paradigm in rats.

BACKGROUND: The association between smoking and depression has been widely investigated. Smoking cessation is known to induce depression to a variable extent, and patients with a history of depression are more likely to experience depressive symptoms. To investigate the hypothesis that nicotine may have an antidepressantlike effect, we used learned helpless rats as an animal model of depression. METHODS: Learned helplessness was produced according to our previous method. Learned helpless rats were implanted with nicotine and escape test was performed at 7 and 14 days after the implantation. RESULTS: The number of escape failure in the rats receiving 1.5 mg/kg/day of nicotine was significantly reduced (p < .05) compared to control at day 14. Furthermore, this effect was blocked when the nicotinic receptor antagonist mecamylamine was coadministered. CONCLUSIONS: These results suggest that chronic nicotine may act as an antidepressant, probably via nicotinic receptors.

Animals↗
PubMed1998

Changes in high K+-evoked serotonin release and serotonin 2A/2C receptor binding in the frontal cortex of rats with thioacetamide-induced hepatic encephalopathy.

Serotonergic systems were investigated in the frontal cortex of rats with thioacetamide (TAA)-induced acute hepatic encephalopathy (HE). Extracellular basal levels of 5-HT showed no difference between control and HE animals, whereas the levels of 5-HIAA were significantly increased in HE rats. Unlike basal levels, high K+-evoked 5-HT release was significantly higher in HE rats than controls. Bmax of (+/-)-1-(2,5-dimethoxy-4-[125I] iodophenyl)-2-aminopropane ([125I] DOI) binding, mainly labeling postsynaptic 5-HT2A receptors, was significantly decreased without any change in Kd in HE rats. These results suggest that there is no change in basal 5-HT release in the cortex of rats with TAA-induced HE despite the increase in intraneuronal 5-HT metabolism and in the size of releasable 5-HT pool, and that serotonergic neurotransmission via 5-HT2A receptor is altered in the brain area of rats with HE.

Acute Disease↗