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1.
Clin Psychopharmacol Neurosci ; 13(1): 109-12, 2015 Apr 30.
Article in English | MEDLINE | ID: mdl-25912544

ABSTRACT

Clozapine has been demonstrated to be useful for treating refractory schizophrenia. However, hypersalivation occurs in 31.0- 97.4% of the patients treated with clozapine. Accordingly, some patients who are disturbed by their hypersalivation refuse to continue with clozapine treatment. This study investigated the efficacy of the anticholinergic agent scopolamine butylbromide against clozapine-induced hypersalivation. Five schizophrenia patients were coadministered scopolamine butylbromide (30-60 mg/ day) for 4 weeks. At the baseline and after 4 weeks' treatment, we subjectively evaluated hypersalivation using a visual analog scale and objectively assessed it using the Drooling Severity Scale and Drooling Frequency Scale. As a result, improvements in the patients' Drooling Severity Scale and Drooling Frequency Scale scores, but no improvements in their visual analog scale scores, were observed after scopolamine butylbromide treatment. These results indicate that at least some schizophrenic patients with clozapine-induced hypersalivation would benefit from scopolamine butylbromide treatment. We conclude that clozapine-induced hypersalivation is one factor of stress to patients. Subjective hypersalivation was not improved, but objective hypersalivation was, by scopolamine butylbromide treatment. However, scopolamine butylbromide and clozapine possess anticholinergic effects so clinicians should closely monitor patients who take scopolamine butylbromide.

2.
Asian J Psychiatr ; 6(3): 200-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23642976

ABSTRACT

Japan approved clozapine for treatment-resistant schizophrenia in June 2009. The aim of this study was to evaluate clozapine's efficacy and tolerability in Japanese patients. A twelve-week, single-arm clinical trial of clozapine in treatment-resistant schizophrenia inpatients, was conducted under real-world conditions using raters masked for type of antipsychotic. Thirty-eight patients were recruited, with 33 (86.8%) completing the trial. At week 12, clozapine was associated with significant improvement in the Positive and Negative Syndrome Scale (PANSS) total (p < 0.0001), PANSS positive (p < 0.0001), negative (p = 0.0055) and general subscale scores (p < 0.0001). Significant improvements occurred in all PANSS scores by week 4, the first post-baseline psychopathology rating. Altogether, 50.0% of patients showed ≥20% reduction in PANSS total score, 20.6% had ≥30% reduction and 14.7% had >40% reduction. Eighteen patients (47.4%) were discharged before week 12. However, all patients experienced ≥1 adverse event. Two of 38 patients (5.2%) dropped out due to moderate leucopenia and one of them developed agranulocytosis after stopping clozapine. However, both patients recovered. Eight adverse events (hypersalivation, fatigue, sedation, constipation, insomnia, nausea/vomiting, chest pain and leucopenia) were observed in 34-79% of patients. These findings suggest that clozapine is beneficial in Japanese treatment-resistant schizophrenia patients. However, attention should be paid to patients' adverse events.


Subject(s)
Antipsychotic Agents/administration & dosage , Clozapine/administration & dosage , Schizophrenia/drug therapy , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Drug Administration Schedule , Drug Resistance , Female , Humans , Male , Middle Aged , Treatment Outcome
3.
Psychiatr Genet ; 23(3): 117-23, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23474461

ABSTRACT

OBJECTIVES: To search for schizophrenia susceptibility loci, we carried out a case-control study using 28601 microsatellite markers distributed across the entire genome. MATERIALS AND METHODS: To control the highly multiple testing, we designed three sequential steps of screening using three independent sets of pooled samples, followed by the confirmatory step using an independent sample set (>2200 case-control pairs). RESULTS: The first screening using pooled samples of 157 case-control pairs showed 2966 markers to be significantly associated with the disorder (P<0.05). After the second and the third screening steps using pooled samples of 150 pairs each, 374 markers remained significantly associated with the disorder. We individually genotyped all screening samples using a total of 1536 tag single nucleotide polymorphisms (SNPs) located in the vicinity of ~200 kb from the 59 positive microsatellite markers. Of the 167 SNPs that replicated the significance, we selected 31 SNPs on the basis of the levels of P values for the confirmatory association test using an independent-sample set. The best association signal was observed in rs13404754, located in the upstream region of SLC23A3. We genotyped six additional SNPs in the vicinity of rs13404754. Significant associations were observed in rs13404754, rs6436122, and rs1043160 in the cumulative samples (2617 cases and 2698 controls) (P=0.005, 0.035, and 0.011, respectively). These SNPs are located in the linkage disequilibrium block of 20 kb in size containing SLC23A3, CNPPD1, and FAM134A genes. CONCLUSION: Genome-wide association study using microsatellite markers suggested SLC23A3, CNPPD1, and FAM134A genes as candidates for schizophrenia susceptibility in the Japanese population.


Subject(s)
Genetic Markers , Genome-Wide Association Study , Microsatellite Repeats/genetics , Schizophrenia/genetics , Adult , Case-Control Studies , Female , Humans , Japan , Male , Middle Aged , Polymorphism, Single Nucleotide
5.
BMJ Open ; 2(3)2012.
Article in English | MEDLINE | ID: mdl-22566608

ABSTRACT

OBJECTIVES: The present study aimed to validate screening tools that could be used to identify depression among workers. DESIGN: Diagnostic test study. SETTINGS: Workers from three Japanese companies agreed to participate. PARTICIPANTS: Recruitment for the group 1 occurred between January 2001 and February 2004, and 89 participants (81 men and 8 women with a mean age of 38.4±6.6 years) (98.8%) took part in the study. Recruitment for the group 2 occurred between July 2000 and February 2004, and 1500 participants (1408 men and 92 women with a mean age of 40.9±7.2 years) (94.2%) took part in the study. Demographic data are shown in supplementary table 1. PRIMARY AND SECONDARY OUTCOME MEASURES: the Beck Depression Inventory (BDI) and a two-question case-finding instrument (TQI) were administered to 89 workers and Mini-International Neuropsychiatric Interview was conducted to verify the diagnosis of depression. A second group of 1500 workers completed the BDI and TQI to detect possible sample bias for the distribution of depression. Specificity, sensitivity and positive predictive value were calculated in order to obtain the optimal cut-off scores for BDI and TQI and receiver operating characteristic curves, and Youden Index were applied to further refine the optimal cut-off scores. RESULTS: When paired together, BDI score ≥10 and TQI score of 2 adequately identified workers who had major depressive disorder and those who had other psychiatric disorders that are frequently comorbid with major depressive disorder. CONCLUSIONS: The combination of BDI score ≥10 and TQI score of 2 can adequately screen for current and potential cases of depression among workers. Furthermore, BDI and TQI offer the advantage of being relatively easy to administer to a large number of workers. Early detection of depression could improve treatment outcomes and decrease economic burden. TRIAL REGISTRATION: [corrected]

6.
Psychiatry Clin Neurosci ; 64(3): 268-73, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20602727

ABSTRACT

AIMS: The aim of this study was to analyze the relation between treatment response and the duration of untreated illness (DUI) in 133 outpatients with the first major depressive disorder (MDD) episode. METHODS: A logistic regression was performed with DUI, sex, age at onset, and score for 17 items on the Hamilton Depression Rating Scale at the time of start of fluvoxamine treatment as the explanatory variables, and the response and the remission as the outcome variables. RESULTS: Regression analysis showed significant association between the response and DUI (P < 0.0001), and between the remission and DUI (P < 0.0001), respectively. The remission rate gradually decreased with longer DUI. CONCLUSION: Early treatment of first depressive episodes is important because a shorter DUI implied better remission outcomes.


Subject(s)
Age of Onset , Antidepressive Agents/therapeutic use , Depressive Disorder, Major/drug therapy , Fluvoxamine/therapeutic use , Adult , Aged , Female , Humans , Male , Middle Aged , Time Factors , Treatment Outcome
7.
World J Biol Psychiatry ; 11(2 Pt 2): 431-8, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19353385

ABSTRACT

Schizophrenia is a common psychiatric disorder characterized by disturbances of cognition, emotion and social functioning. There are few studies investigating a possible genetic basis for the underlying mechanism of cognitive dysfunctions. A genetic variation in the dysbindin gene (DTNBP1: dystrobrevin binding protein 1), a susceptibility gene for schizophrenia, has been reported to be associated with general cognitive ability and cognitive decline in patients with schizophrenia. Although profound disturbances of memory performance are observed in schizophrenia, only one study has reported a relationship between this gene and spatial working memory in a Caucasian population. We examined a possible association between a protective haplotype of DTNBP1 for developing schizophrenia and memory performance measured by the Wechsler Memory Scale-Revised (WMS-R) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in 165 healthy volunteers and 70 patients with schizophrenia in a Japanese population. Healthy controls that carry the protective haplotype showed higher performance in several memory domains measured by the WMS-R than those who did not. Genotype effect on memory performance was not observed in patients with schizophrenia. This haplotype did not affect IQ and its sub-scores as measured by the Wechsler Adult Intelligence Scale-Revised in both groups. These data suggest that DTNBP1 may have impact on parts of memory functions.


Subject(s)
Carrier Proteins/genetics , Memory/physiology , Polymorphism, Single Nucleotide/genetics , Adult , Dysbindin , Dystrophin-Associated Proteins , Female , Genotype , Haplotypes , Humans , Male , Middle Aged , Schizophrenia/genetics , Schizophrenic Psychology , Wechsler Scales
8.
Am J Med Genet B Neuropsychiatr Genet ; 147B(4): 531-4, 2008 Jun 05.
Article in English | MEDLINE | ID: mdl-18085546

ABSTRACT

Altered dopamine D2 receptor (D2R) is hypothesized to be a susceptibility factor for major psychosis. Recent studies showed that a new intracellular protein, prostate apoptosis response 4 (Par-4), plays a critical role in D2R signaling. We conducted a genetic association analysis between Par-4 gene (PAWR) and schizophrenia and mood disorders in a Japanese population (schizophrenia: 556 cases, bipolar disorder (BP): 150 cases, major depressive disorder (MDD): 312 cases and 466 controls). Applying the recommended 'gene-based' association analysis, we selected five tagging SNPs in PAWR from the HapMap database. No significant association was obtained found with schizophrenia or MDD or BP. We found a significant association of one tagging SNP with BP in a genotype-wise analysis (P = 0.0396); however, this might be resulted from type I error due to multiple testing (P = 0.158 after SNPSpD correction). Considering the size of our sample and strategy, our results suggest that the PAWR does not play a major role in schizophrenia or mood disorders in the Japanese population.


Subject(s)
Apoptosis Regulatory Proteins/genetics , Mood Disorders/genetics , Schizophrenia/genetics , Adult , Asian People/genetics , Bipolar Disorder , Case-Control Studies , Depressive Disorder, Major , Female , Genetic Predisposition to Disease , Humans , Linkage Disequilibrium , Male , Middle Aged , Polymorphism, Single Nucleotide
9.
Int J Neuropsychopharmacol ; 11(2): 261-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-17697394

ABSTRACT

Selective serotonin reuptake inhibitor (SSRI)-induced nausea can be severe enough to lead to early treatment discontinuation. However, it is currently not possible to predict the occurrence of nausea before the initiation of SSRI treatment. In this study, we investigated the effect of genetic polymorphisms in the 5-hydroxytryptamine type 2A, 3A, and 3B (5-HT3B) receptors, 5-HT transporter, and CYP2D6 genes on the incidence of paroxetine-induced nausea. A consecutive series of 72 Japanese patients with depressive or anxiety disorders were treated with paroxetine. Paroxetine-induced nausea was assessed by a pharmacist and was observed in 29.2% of the patients. A significant (nominal p=0.00286) association was found between the incidence of nausea and the -100_-102AAG insertion/deletion polymorphism of the 5-HT3B receptor gene. No significant associations were observed between the other genetic polymorphisms and the incidence of nausea. The -100_-102AAG deletion variant of the 5-HT3B receptor gene may affect paroxetine-induced nausea.


Subject(s)
Antidepressive Agents, Second-Generation/adverse effects , Anxiety Disorders/drug therapy , Depressive Disorder/drug therapy , Nausea/etiology , Paroxetine/adverse effects , Polymorphism, Genetic , Receptors, Serotonin, 5-HT3/genetics , Selective Serotonin Reuptake Inhibitors/adverse effects , Adolescent , Adult , Aged , Antidepressive Agents, Second-Generation/blood , Anxiety Disorders/genetics , Depressive Disorder/genetics , Female , Genetic Predisposition to Disease , Humans , Incidence , Japan , Male , Middle Aged , Nausea/chemically induced , Nausea/genetics , Paroxetine/blood , Risk Factors , Selective Serotonin Reuptake Inhibitors/blood , Severity of Illness Index
10.
Prog Neuropsychopharmacol Biol Psychiatry ; 32(1): 204-8, 2008 Jan 01.
Article in English | MEDLINE | ID: mdl-17822820

ABSTRACT

Lithium is one of the most commonly used drugs for the treatment of bipolar disorder. To prescribe lithium appropriately to patients, predictors of response to this drug were explored, and several genetic markers are considered to be good candidates. We previously reported a significant association between genetic variations in the breakpoint cluster region (BCR) gene and bipolar disorder. In this study, we examined a possible relationship between response to maintenance treatment of lithium and Asn796Ser single-nucleotide polymorphism in the BCR gene. Genotyping was performed in 161 bipolar patients who had been taking lithium for at least 1 year, and they were classified into responders for lithium mono-therapy and non-responders. We found that the allele frequency of Ser796 was significantly higher in non-responders than in responders. Further investigation is warranted to confirm our findings.


Subject(s)
Antimanic Agents/therapeutic use , Bipolar Disorder/genetics , Bipolar Disorder/prevention & control , Lithium Compounds/therapeutic use , Mutation, Missense/genetics , Polymorphism, Single Nucleotide/genetics , Proto-Oncogene Proteins c-bcr/genetics , Adult , Analysis of Variance , Asparagine/genetics , Bipolar Disorder/classification , Brief Psychiatric Rating Scale , Female , Gene Frequency , Genotype , Humans , Male , Middle Aged , Pharmacogenetics , Serine/genetics
11.
Psychiatr Genet ; 17(4): 227-31, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17621166

ABSTRACT

BACKGROUND: Microarray studies of schizophrenic brains revealed decreases in the expression of myelin and oligodendrocyte-related genes. Of these genes, sex-determining region Y-box 10 (SOX10) is a major transcription factor modulating the expression of proteins involved in neurogenesis and myelination. The SOX10 gene is located on chromosome 22q13.1, a region repeatedly reported to show positive signals in linkage studies on schizophrenia. OBJECTIVE: This study was conducted to clarify the exact role of SOX10 in the pathophysiology of schizophrenia. METHODS: We performed an association analysis of SOX10 in a Japanese population of 915 schizophrenic patients and 927 controls. Genotyping was carried out using polymerase chain reaction restriction fragment length polymorphism. MAIN RESULTS: One single nucleotide polymorphism of the SOX10 gene (rs139,887) was selected as a haplotype tag single nucleotide polymorphism using 96 controls. A significant association was observed in the genotype and allelic frequency of this single nucleotide polymorphism between schizophrenic patients and controls (P=0.025 and P=0.009, respectively). Especially, a significant association was found in male patients, but not female patients. We also performed a mutational search of the whole coding region, branch site, and promoter region of SOX10 in 96 schizophrenic patients, but no potential functional polymorphisms were detected. CONCLUSION: This study suggests that the SOX10 gene is related to the development of schizophrenia in the Japanese population.


Subject(s)
DNA-Binding Proteins/genetics , High Mobility Group Proteins/genetics , Schizophrenia/genetics , Transcription Factors/genetics , Adult , Aged , Chromosome Mapping , Chromosomes, Human, Pair 22 , DNA Primers , Female , Genetic Predisposition to Disease , Genotype , Humans , Japan , Male , Middle Aged , Mutation , Oligonucleotide Array Sequence Analysis , Reference Values , SOXE Transcription Factors
12.
Schizophr Res ; 91(1-3): 22-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17303389

ABSTRACT

Postmortem studies regarding schizophrenia revealed altered expression of genes related to gamma-amino butyric acid neurotransmission system. One of the most consistent findings is the reduced level of 67 kDa glutamic acid decarboxylase isoform (GAD(67)). Moreover, several studies reported positive associations between the GAD(67) gene (GAD1) and schizophrenia. These reasons, motivated us to carry out replication study regarding association between GAD1 (fourteen tagging SNPs) and schizophrenia in Japanese population (562 schizophrenic patients and 470 controls). However we couldn't confirm significant association that had been previously reported. Considering size of our sample and strategy that corresponds well with the approaches used in gene-based association analysis, our conclusion is that GAD1 does not play a major role in schizophrenia in Japanese population.


Subject(s)
Asian People/genetics , Asian People/statistics & numerical data , Gene Expression/genetics , Glutamate Decarboxylase/genetics , Glutamate Decarboxylase/metabolism , Isoenzymes/genetics , Isoenzymes/metabolism , Schizophrenia/ethnology , Schizophrenia/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Female , Genetic Markers , Genotype , Haplotypes/genetics , Humans , Japan , Linkage Disequilibrium/genetics , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , gamma-Aminobutyric Acid/metabolism
13.
Brain Res ; 1125(1): 85-93, 2006 Dec 13.
Article in English | MEDLINE | ID: mdl-17113049

ABSTRACT

We investigated the relationship between temperamental predisposition and brain structure by using a standard questionnaire and high-resolution T1-weighted magnetic resonance image (MRI) in normal young volunteers. Fifty-six subjects completed the Japanese version of the Temperament and Character Inventory (TCI, 125 items) and underwent an MRI acquisition of the brain. The gray matter (GM) was extracted from the whole brain image of the subjects and normalized to the standard brain template using statistical parametric mapping and the optimized voxel-based morphometry (VBM) method. When the score on the harm avoidance (HA) subscale was used as a dependent variable, the multiple regression analysis revealed that the HA score positively correlated with the volume of the part of left amygdala. The region-of-interest analysis showed that the correlation was significant in the female subjects but not in the male subjects. The correlation was significant even after the effects of age, depression score, and total GM volume were taken into account. The differential correlation between the sexes may be caused by differences in hormonal condition and the vulnerability of women to socio-psychological stress. In addition, the novelty seeking (NS) score positively correlated with the GM of the left middle frontal gyrus. The volume of the tail of the right caudate nucleus positively correlated with the reward dependence (RD) score. With regard to the NS and RD scores, no significant sex difference was observed in the correlation. These results indicate that the temperamental traits measured using the questionnaire may have a morphological basis in the human brain.


Subject(s)
Amygdala/anatomy & histology , Amygdala/physiology , Harm Reduction/physiology , Magnetic Resonance Imaging , Sex Characteristics , Temperament/physiology , Adult , Body Weights and Measures , Brain Mapping , Female , Functional Laterality/physiology , Humans , Image Processing, Computer-Assisted/methods , Male , Personality Inventory , Predictive Value of Tests
14.
Schizophr Res ; 88(1-3): 245-50, 2006 Dec.
Article in English | MEDLINE | ID: mdl-17010574

ABSTRACT

Several lines of evidence suggest that disturbance of myelin-related genes is associated with the etiology of schizophrenia. Recently, the 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP) gene and the oligodendrocyte lineage transcription factor 2 (OLIG2) gene were reported to be related to the development of schizophrenia, based on the results of genetic association and microarray studies. In the present study, no significant association with schizophrenia was observed by single-marker or haplotype analysis for 6 tag SNPs of these genes (759 cases, 757 controls). These findings suggest that CNP and OLIG2 are unlikely to be related to the development of schizophrenia in the Japanese population.


Subject(s)
2',3'-Cyclic-Nucleotide Phosphodiesterases/genetics , Asian People/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Nerve Tissue Proteins/genetics , Schizophrenia/ethnology , Schizophrenia/genetics , Adult , Female , Genotype , Humans , Linkage Disequilibrium/genetics , Male , Middle Aged , Myelin Sheath/genetics , Oligodendrocyte Transcription Factor 2 , Oligonucleotide Array Sequence Analysis/methods , Polymerase Chain Reaction
15.
Hum Mol Genet ; 15(20): 3024-33, 2006 Oct 15.
Article in English | MEDLINE | ID: mdl-16959794

ABSTRACT

Disrupted-in-schizophrenia 1 (DISC1), identified in a pedigree with a familial psychosis with the chromosome translocation (1:11), is a putative susceptibility gene for psychoses such as schizophrenia and bipolar disorder. Although there are a number of patients with major depressive disorder (MDD) in the family members with the chromosome translocation, the possible association with MDD has not yet been studied. We therefore performed an association study of the DISC1 gene with MDD and schizophrenia. We found that Cys704 allele of the Ser704Cys single-nucleotide polymorphism (SNP) was associated with an increased risk of developing MDD (P=0.005, odds ratio=1.46) and stronger evidence for association in a multi-marker haplotype analysis containing this SNP (P=0.002). We also explored possible impact of Ser704Cys on brain morphology in healthy volunteers using MR imaging. We found a reduction in gray matter volume in cingulate cortex and a decreased fractional anisotropy in prefrontal white matter of individuals carrying the Cys704 allele compared with Ser/Ser704 subjects. In primary neuronal culture, knockdown of endogenous DISC1 protein by small interfering RNA resulted in the suppression of phosphorylation of ERK and Akt, whose signaling pathways are implicated in MDD. When effects of sDISC1 (Ser704) and cDISC1 (Cys704) proteins were examined separately, phosphorylation of ERK was greater in sDISC1 compared with cDISC1. A possible biological mechanism of MDD might be implicated by these convergent data that Cys704 DISC1 is associated with the lower biological activity on ERK signaling, reduced brain gray matter volume and an increased risk for MDD.


Subject(s)
Brain/pathology , Depressive Disorder, Major/genetics , Extracellular Signal-Regulated MAP Kinases/metabolism , MAP Kinase Signaling System , Nerve Tissue Proteins/genetics , Polymorphism, Single Nucleotide , Adult , Amino Acid Substitution , Animals , Case-Control Studies , Depressive Disorder, Major/blood , Female , Green Fluorescent Proteins , Humans , Magnetic Resonance Imaging , Male , Middle Aged , RNA, Small Interfering/genetics , Rats , Transfection
16.
Am J Med Genet B Neuropsychiatr Genet ; 141B(8): 929-34, 2006 Dec 05.
Article in English | MEDLINE | ID: mdl-16921495

ABSTRACT

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.


Subject(s)
Bulimia Nervosa/genetics , Genetic Predisposition to Disease/genetics , Peptide Hormones/genetics , Polymorphism, Single Nucleotide/genetics , Adult , Female , Gene Frequency , Genotype , Ghrelin , Haplotypes/genetics , Humans , Linkage Disequilibrium
17.
Psychiatr Genet ; 16(2): 49-50, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16538178

ABSTRACT

Lithium is a first-line agent for the treatment of bipolar disorder. A significant association between the Val66Met polymorphism of the brain-derived neurotrophic factor gene and bipolar disorder has been reported. We investigated whether this polymorphism is associated with the response to lithium treatment in Japanese patients with bipolar disorder. Patients had been treated with lithium carbonate for more than 1 year, and the response was retrospectively evaluated. No significant differences were found in the genotype distribution or allele frequency between responders and non-responders. Our results suggested that the brain-derived neurotrophic factor Val66Met polymorphism might not greatly contribute to the efficacy of lithium in bipolar disorder.


Subject(s)
Antimanic Agents/pharmacokinetics , Bipolar Disorder/genetics , Brain-Derived Neurotrophic Factor/genetics , Drug Resistance/genetics , Lithium Carbonate/pharmacokinetics , Polymorphism, Single Nucleotide , Adult , Alleles , Amino Acid Substitution , Antimanic Agents/therapeutic use , Bipolar Disorder/drug therapy , Brain-Derived Neurotrophic Factor/physiology , Female , Gene Frequency , Genotype , Humans , Japan , Lithium Carbonate/therapeutic use , Male , Middle Aged , Retrospective Studies
18.
Schizophr Res ; 83(2-3): 179-83, 2006 Apr.
Article in English | MEDLINE | ID: mdl-16504480

ABSTRACT

It has been reported that expression of the chromogranin A (CHGA) gene is reduced in the prefrontal cortex and cerebrospinal fluid of patients with schizophrenia. Single-marker and haplotype analyses of SNPs within the CHGA gene were performed in 633 subjects with schizophrenia and 589 healthy controls. A significant association with schizophrenia was observed to one SNP marker, rs9658635 (p=0.0269), and with a 2 marker haplotype (p=0.0016). Significant association of rs9658635 was then replicated in a second independent cohort (377 schizophrenia and 338 control samples) (p=0.007). These results suggest that the CHGA gene is associated with the risk of developing schizophrenia in the Japanese population.


Subject(s)
Chromogranins/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic/genetics , Schizophrenia/genetics , Adult , Case-Control Studies , Chromogranin A , Female , Gene Frequency , Genotype , Humans , Japan/epidemiology , Male , Middle Aged , Schizophrenia/epidemiology , Sequence Analysis
19.
Schizophr Res ; 82(2-3): 185-9, 2006 Feb 28.
Article in English | MEDLINE | ID: mdl-16442780

ABSTRACT

Several investigations suggest that complexin may be a schizophrenia-susceptibility factor. We conducted a genetic association analysis between complexin genes (CPLX1 and CPLX2) and schizophrenia in Japanese patients (377 cases and 341 controls). Ten and eleven haplotype-tagging (ht)SNPs in CPLX1 and CPLX2, respectively, were selected. Only one htSNP (rs930047 in CPLX2) in allele-wise analysis showed significance, and even this disappeared with an increased sample size (563 cases and 519 controls: P = .757). Haplotype-wise analysis showed a weak association with a combination of htSNPs in CPLX2 (P = .0424), but this may be a result of type I error due to multiple testing. Our results suggest that complexin genes do not play a major role in schizophrenia in Japanese patients.


Subject(s)
Asian People/genetics , Nerve Tissue Proteins/genetics , Schizophrenia/genetics , Adaptor Proteins, Vesicular Transport , Adult , Alleles , Female , Gene Expression/physiology , Genetic Predisposition to Disease/genetics , Genotype , Haplotypes , Humans , Linkage Disequilibrium , Male , Middle Aged , Polymorphism, Single Nucleotide , Schizophrenia/diagnosis , Statistics as Topic
20.
Int J Neuropsychopharmacol ; 9(1): 77-81, 2006 Feb.
Article in English | MEDLINE | ID: mdl-15982448

ABSTRACT

Recent evidence suggests that the AKT1-GSK3beta signalling cascade partially mediates dopamine-dependent behaviours. In relation to the pathophysiology of schizophrenia or methamphetamine (Meth) use disorder, AKT1 is a good candidate gene for such conditions. For schizophrenia, positive associations of SNPs and AKT1 haplotypes were reported in US and Japanese samples. To evaluate the association between AKT1 and Meth-use disorder, we conducted a case-control study of Japanese samples (182 patients and 437 controls). A positive association between a SNP and haplotypes was found, and the 'signal' SNP was the same SNP found to be associated with US schizophrenia, but not with Japanese schizophrenia. Our results indicate that AKT1 may play a possible role in the development of Meth-use disorder. Further investigation of these associations, together with evidence from previous animal studies, may open the way to elucidation of the pathophysiology of this condition.


Subject(s)
Amphetamine-Related Disorders/genetics , Proto-Oncogene Proteins c-akt/genetics , Adult , Case-Control Studies , Female , Gene Frequency , Genetic Predisposition to Disease , Haplotypes , Humans , Japan , Male , Methamphetamine , Polymorphism, Single Nucleotide
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