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Biomedical subjects

G Yagi

Publications and source records attributed to G Yagi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Dopamine D2, D3 and D4 receptor and transporter gene polymorphisms and mood disorders.

Disturbances in dopaminergic systems have been implicated in the etiology of mood disorders. Although genetic factors also play an important role, no major gene has been identified. We conducted an association study using the dopamine D2, D3 and D4 receptor, and transporter gene polymorphisms, comparing 101 mood-disorder patients (52 bipolar and 49 unipolar) and 100 controls. Our results suggest that there is a significant association between the dopamine D4 receptor gene and mood disorders, especially major depression, but no association between the other polymorphisms and mood disorders. Further investigations are needed to clarify the clinical significance of this association in the pathophysiology of mood disorders.

Adult↗
PubMed1996

Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode.

To investigate the possible role of the dopamine transporter (DAT) gene in determining the phenotype in human subjects, allele frequencies for the 40-bp variable number of tandem repeats (VNTR) polymorphism at this site were compared between 117 Japanese normal controls and 118 schizophrenic patients, including six subgroups: early-onset, those with a family history, and those suffering from one of the following psychiatric symptoms at their first episode: delusion and hallucination; disorganization; bizarre behavior; and negative symptoms. No significant differences were observed between the group as a whole or any subgroup of schizophrenic patients and controls. The results indicate that VNTR polymorphism in the DAT gene is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.

Adult↗
PubMed1996

Nilvadipine is effective for chronic schizophrenia in a double-blind placebo-controlled study. off.

We investigated the efficacy of nilvadipine, a calcium channel inhibitor, for psychiatric symptoms and tardive dyskinesia in 30 patients with chronic schizophrenia in a placebo-controlled double-blind crossover study. The total scores of the Brief Psychiatric Rating Scale decreased significantly when the patients were on nilvadipine compared with placebo. Improvement was particularly significant in emotional withdrawal and uncooperativeness. Nilvadipine was not effective, however, for tardive dyskinesia. No adverse effects, such as hypotension, occurred.

Adult↗
PubMed1996

Improvement of schizophrenic symptoms and changes in plasma HVA concentrations, plasma anti-D2 and anti-5-HT2 receptor activities with clozapine.

In order to investigate the biological mechanisms underlying the clinical efficacy of clozapine, 200 mg/day of clozapine was added to the drug regimens of 19 patients with chronic, anti-psychotic-resistant schizophrenia, and the plasma homovanillic acid (HVA), clozapine concentrations, anti-dopamine D2 and anti-serotonin 5-HT2 receptor activities were measured. After 28 days, six patients showed an improvement of more than 20% over baseline Brief Psychiatric Rating Scale (BPRS) scores. Mean plasma HVA concentrations and anti-D2 receptor activities did not change significantly in the entire group or in the six patients showing improvement. However, anti-5-HT2 receptor activities increased significantly in all 19 patients. Changes in BPRS scores did not correlate significantly with changes in plasma HVA or with changes in clozapine concentrations, or with anti-D2 and anti-5-HT2 receptor activities.

Adult↗
PubMed1996

Effectiveness of shakuyaku-kanzo-to in neuroleptic-induced hyperprolactinemia: a preliminary report.

We investigated the efficacy of Shakuyaku-kanzo-to (TJ-68) in neuroleptic-induced hyperprolactinemia in 11 treated schizophrenic patients. The mean plasma prolactin level decreased significantly from 28.9 +/- 14.5 ng/mL at baseline to 22.0 +/- 15.2 ng/mL at 4 weeks. Potassium levels did not change significantly. Neither the exacerbation of psychosis nor other adverse effects occurred.

Adult↗
PubMed1996

Current topics in neuroleptic-induced extrapyramidal symptoms in Japan.

This article reviews current topics in neuroleptic-induced extrapyramidal symptoms in Japan, focusing especially on the clinical features of akathisia and dystonia. Akathisia is a common side effect associated with antipsychotic drugs. It is most commonly characterized by subjective inner restlessness and objective motor signs, especially in the lower extremities. The mechanisms underlying akathisia remain unclear and controversial; however, an increase in the activity of beta-adrenergic systems relative to dopaminergic systems has been hypothesized, based on clinical therapeutic observations that beta-blocking agents are effective in this condition. A Japanese version of the Barnes Akathisia Scale has recently been established and uses a standardized videotape method for its precise evaluation. Various acute and chronic manifestations of neuroleptic-induced dystonia have been reported in Japan, including blepharospasm, difficulty in opening the eye lids, torticollis, retrocollis, oculogyric crisis, and Pisa syndrome. This review also introduces several other topics related to drug-induced extrapyramidal symptoms in Japan. These include; 1) the Drug-Induced Extra-Pyramidal Symptoms Scale (DIEPSS), which has recently been established, 2) studies on the discontinuation of anticholinergic drugs, and 3) a summary of extrapyramidal symptoms induced by drugs other than neuroleptics.

Akathisia, Drug-Induced↗
PubMed1996

Negative symptoms in nondeficit syndrome respond to neuroleptic treatment with changes in plasma homovanillic acid concentrations.

Deficit syndrome (DS) in schizophrenia is characterized by serious, chronic, and primary negative symptoms. We investigated differences in response to neuroleptic treatment between 8 DS patients and 6 nondeficit syndrome (NDS) patients who had the selective dopamine-D2 receptor blocker bromperidol added to their neuroleptic regimens. First, 9 mg/d was administered for 4 weeks, followed by 18 mg/d for another 4 weeks. Plasma homovanillic acid (pHVA) and plasma bromperidol concentrations were measured, and psychiatric symptoms were scored. In the NDS patients, both positive and negative symptoms improved. However, only the positive symptom scores changed in the DS patients. On day 4, pHVA concentrations of the NDS patients alone were significantly elevated. Plasma bromperidol concentrations did not differ between the groups. These results suggest that bromperidol exerts different effects on negative symptoms and pHVA concentrations between NDS and DS patients, effects that are unrelated to plasma bromperidol concentrations.

Adult↗
PubMed1995

Schizophrenic patients with deficit syndrome have higher plasma homovanillic acid concentrations and ventricular enlargement.

In order to investigate the biological characteristics of deficit syndrome in schizophrenia (Carpenter et al 1988), we examined cerebroventricular ratios (CVRs) and plasma concentrations of homovanillic acid (HVA) in a group of schizophrenic inpatients with deficit syndrome (n = 20) and in a control group of age- and sex-matched schizophrenic inpatients without deficit syndrome (n = 20). Symptoms and intelligence levels were measured using the Brief Psychiatric Rating Scale (BPRS) and the Wechsler Adult Intelligence Scale (WAIS), respectively. Patients in the deficit group had significantly higher CVRs as well as significantly elevated plasma HVA concentrations when compared with patients in the nondeficit group. We also found that the mean total WAIS score in the deficit group was significantly lower than that in the nondeficit group. These findings suggest the biological heterogeneity of schizophrenia. Increased central dopaminergic turnover, as indicated by higher plasma HVA concentrations, may partially account for the pathogenesis of deficit syndrome.

Adult↗
PubMed1995

Dopamine D3 receptor gene polymorphism and the psychiatric symptoms seen in first-break schizophrenic patients.

To investigate the possible effect of polymorphism at the BalI site of the dopamine D3 receptor gene (DRD3) on the phenotype in human subjects, allele and genotype frequencies for this polymorphic site were examined in 113 schizophrenic patients, including six subgroups, and 48 normal controls. The schizophrenic subgroups included patients with early onset, those with a family history, and those who suffered from one of the following psychiatric symptoms at their first episode: (1) delusion and hallucination; (2) disorganization; (3) bizarre behavior; and (4) negative symptoms. No significant differences were observed in genotype, allele and homozygosity frequencies between the whole group or any subgroup of schizophrenic patients and the controls. The present results indicate that polymorphism at the BalI site of the DRD3 is unlikely to be a major contributor to any of the psychiatric parameters examined in the present population of schizophrenic subjects.

Adult↗
PubMed1995

Effectiveness of nilvadipine in two cases of chronic schizophrenia.

Nilvadipine is a calcium channel inhibitor used commonly for the treatment of cerebrovascular insufficiency. We observed two patients with schizophrenia whose psychiatric symptoms and tardive dyskinesia improved after the addition of nilvadipine to their antipsychotic drug regimen. The total score of the brief psychiatric rating scale (BPRS) in case 1 fell from 56 to 42 after 8 weeks on nilvadipine; while that of case 2 fell from 44 to 32. The total score of the abnormal involuntary movement scale (AIMS) in case 2 decreased from 12 to 7. No adverse effects occurred during treatment. Nilvadipine may thus offer a new approach to the adjunctive treatment of schizophrenia.

Calcium Channel Blockers↗
PubMed1995

Current topics in tardive dyskinesia in Japan.

This article reviews current topics in tardive dyskinesia (TD), a movement disorder associated with the prolonged use of neuroleptic agents, especially therapeutic and preventive strategies which have been or are now being studied in Japan. Tardive dyskinesia has become a major problem in the clinical psychiatric field since the early 1970s in Japan, lagging behind Western countries by more than 10 years. The average prevalence rate of TD has been estimated as 7.7% in Japan, while it has been reported in the English literature at around 15 to 20%. Clinical trials of treatments for TD have been or are now being performed in Japan with a number of novel compounds, such as ceruletide, meclofenoxate, and rolipram; however, no effective treatment has yet been established and measures to prevent TD have therefore been emphasized. These include (i) the development of new antipsychotic drugs which are free from TD, (ii) the identification of risk factors from prospective longitudinal studies, and (iii) the investigation of genetic variations that could act as a marker to identify especially vulnerable patients within the whole population of patients who need neuroleptic therapy.

Antipsychotic Agents↗
PubMed1995

Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat.

We investigated whether interleukin-1 (IL-1) activity in the rat hypothalamus was increased by immobilization stress (IS), and whether pretreatment with an interleukin-1 receptor antagonist (IL-1Ra) is capable of inhibiting IS-induced elevations of hypothalamic norepinephrine (NE), dopamine (DA), and serotonin (5-HT) and the levels of their metabolites as well as of plasma adrenocorticotropic hormone (ACTH). IL-1 activity was estimated with a bioassay using mouse thymocyte proliferation in the presence of concanavalin A. IL-1Ra was administered directly into the anterior hypothalamus, and monoamines were determined using a microdialysis technique and an HPLC system. First, we found that levels of IL-1 activity in the rat hypothalamus reached a maximum at 60 min after starting IS. Second, IL-1Ra (2 micrograms) significantly inhibited IS-induced increases in hypothalamic NE, DA, and 5-HT levels as well as the levels of their metabolites. In addition, IL-1Ra (2 micrograms) also inhibited the IS-induced elevation of plasma ACTH levels. Third, timing effects of IL-1Ra administration on the IS-induced monoamines or ACTH responses were examined. IL-1Ra (2 micrograms) administered at 5 or 60 min before the start of IS, but not at 5 or 60 min after IS had been started, exerted inhibitory effects on these responses, indicating that the effects of IL-1 occurred within 5 min after the initiation of IS. In summary, these results suggest that IS enhances biologically active IL-1 in the hypothalamus, and that hypothalamic IL-1 plays a role in the regulation of IS-induced responses including elevated monoamine release in the hypothalamus and activation of the hypothalamo-pituitary-adrenal axis. Moreover, since 5 min is too short a time for IS to induce production of IL-1, IS may augment the effects of preexisting IL-1 in the hypothalamus.

Adrenocorticotropic Hormone↗
PubMed1994

Longitudinal changes in symptoms and plasma homovanillic acid levels in chronically medicated schizophrenic patients.

A correlation has been noted between the changes in plasma homovanillic acid concentrations and changes in psychiatric symptoms induced by neuroleptic treatment. Our objective was to determine whether plasma homovanillic acid concentration changed in accordance with the changes in symptoms over time. Twenty-eight chronically medicated schizophrenic inpatients received the same treatment regimen for 1 year. Symptoms and plasma homovanillic acid concentrations were examined every month and whenever conditions deteriorated. Plasma homovanillic acid concentrations were significantly higher in the patients in the worst condition than in the patients in the best condition. Further, when comparing the best and worst conditions of both the positive and negative symptoms, the change in psychiatric rating of positive and negative symptoms was correlated significantly with the change in plasma homovanillic acid level. These results suggest that a change in plasma homovanillic acid concentration can be produced not only by neuroleptic-induced dopaminergic blocking but also by a change in positive and negative symptoms of schizophrenia.

Adult↗
PubMed1994

The first open study of zonisamide, a novel anticonvulsant, shows efficacy in mania.

1. Zonisamide, an anticonvulsant developed in Japan, is structurally similar to serotonin. Zonisamide has been proven to have a pharmacological profile that is very similar to that of carbamazepine. Thus, the effect of zonisamide was examined in 24 psychiatric patients: 15 with bipolar manic state, 6 with schizoaffective manic state, and 3 schizophrenic excitement. 2. Approximately 25% of all the patients and 33% of the bipolar manic patients showed remarkable global improvement with the addition of zonisamide. Approximately 71% of all the patients and 80% of the bipolar group had more than moderate global improvement. 3. No serious adverse reactions were found and no patients required zonisamide withdrawal. One patient developed both leukocytosis and mildly abnormal liver function test. One developed leukocytosis and another reported mild sleepiness. These reactions disappeared when zonisamide was discontinued.

Adult↗
PubMed1994

Inhibition by lithium of cyclic GMP formation without inhibition of nitric oxide generation in the mouse neuroblastoma cell (N1E-115).

We investigated the effects of lithium ion (Li+) on muscarinic receptor-mediated nitric oxide (NO) generation, and guanylate cyclase (GCase) activation using the mouse neuroblastoma clone, N1E-115. The levels of released NO were determined by measuring the levels of nitrite/nitrate in the incubation medium, and the activity of GCase was measured with an assay for cellular cyclic [3H] GMP levels. We determined that Li+ had no effects on muscarinic receptor-activated elevation of nitrite/nitrate levels, which were significantly inhibited by 100 microM L-NG-monomethylarginine, although it has been reported that Li+ inhibits muscarinic receptor-activated cyclic GMP formation in the cells. In addition, Li+ inhibited the cyclic GMP formation induced by an NO donor, sodium nitroprusside (SNP), in both intact cells and a crude cellular homogenate; thus, the inhibition by Li+ of muscarinic receptor-mediated cyclic GMP synthesis appeared to be at the level of GCase, but not NO synthase.

Animals↗
PubMed1994

Affinity of neuroleptics for D1 receptor of human brain striatum.

We determined the inhibition-dissociation constant (Ki) of a number of neuroleptics for D1 receptors of normal human brain tissue using [3H]SCH23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3[benzazepine-7- ol]. SCH23390 had the highest affinity with a Ki of 0.76 nM. Among clinically used drugs, propericiazine showed the highest affinity with a Ki of 10 nM. When neuroleptics were classified according to chemical structures, the Ki values were as follows. Phenothiazines ranged from 10 nM to 250 nM. Butyrophenones ranged from 45 nM to 250 nM. Thioxanthenes ranged from 12 nM to 340 nM. Orthopramines were more than 10,000 nM. The Ki values for the binding site of this study were significantly correlated with those reported in studies using animal brain. The possible relationship between D1 receptors and negative symptoms is discussed.

Aged↗
PubMed1994

Measurement by in vivo brain microdialysis of nitric oxide release in the rat cerebellum.

Using a new method which combines a brain microdialysis technique and measurement of nitrite/nitrate levels by the Griess reaction, it has been proven that activation of N-methyl-D-aspartate (NMDA) receptors in the cerebelli of rats which had been under non-anesthetic and freely moving conditions induces the release of nitric oxide (NO). Since L-NG-monomethylarginine (L-NMMA), which competitively blocks NO synthesis from L-arginine, significantly inhibited the release of nitrite/nitrate from the rat cerebellum, these results indicate that the new method is capable of measuring NO formation from L-arginine following the stimulation of NMDA receptors. This method should prove useful for investigating the relation between brain functions such as behavior, learning and memory and NO in the central nervous system.

Animals↗