Childhood‐onset schizophrenia and tryptophan hydroxylase gene polymorphism

Sekizawa, Takahiro; Iwata, Yasuhide; Nakamura, Kazuhiko; Matsumoto, Hideo; Suzuki, Atsuko; Suzuki, Katsuaki; Sekine, Yoshimoto; Takei, Noriyoshi; Minabe, Yoshio; Mori, Norio

doi:10.1002/ajmg.b.30009

Cited by 13 publications

(14 citation statements)

References 13 publications

(19 reference statements)

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“…Our negative result of TPH1 218A/C was not consistent with the majority of the literature on TPH1 and schizophrenia (Sekizawa et al 2004;Hong et al 2001;Chotai et al 2005), though there have been a few other studies that have reported negative results similar to our own (Paik et al 2000;Serretti et al 1999). Therefore, this relationship remains controversial.…”

Section: Discussioncontrasting

confidence: 77%

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Kim

Yoon

2011

Behav Genet

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Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T variants with schizophrenia. A total of 202 patients with schizophrenia and 165 normal controls were genotyped for HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T single nucleotide polymorphisms (SNPs). In order to assess the severity of a patient's psychiatric symptoms, the brief psychiatric rating scale (BPRS), the positive and negative symptom scale (PANSS), and the Calgary depression scale for Schizophrenia (CDSS) were administered. Genotype and allele frequencies were compared between groups via χ(2) statistics. Associations between the genotypes of candidate SNPs with the severity of symptoms were examined with ANOVA by comparing the mean scores of BPRS, PANSS, and CDSS according to genotype. No significant differences in the genotype distributions and allele frequencies of four SNPs were found between patients with schizophrenia and normal controls. There was a trend towards association of HTR1A C-1019G polymorphism with negative symptom. Negative symptom score of PANSS was lower in the patients with CC genotype than in the G allele carriers. These results suggested that C allele might be associated with lesser negative symptom. More studies are needed to confirm these findings. In the future, we plan to study the associations between schizophrenia and other genetic polymorphisms.

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Section: Discussioncontrasting

confidence: 77%

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Kim

Yoon

2011

Behav Genet

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“…The TPH gene Chotai et al (2003) DSM-IV Italian 147 395 Serretti et al (2001) DSM-IV Italian 210 380 Paik et al (2000) DSM-III-R Korean 217 236 Hong et al (2001) DSM-IV Chinese 196 251 Sekizawa et al (2004) DSM-IV Japanese 51 148 Chao et al (2002) DSM-III-R African-American 41 17 Shinkai et al (2000) DSM-IV Japanese 182 148 The TH gene a Meloni et al (1995) DSM-III French Caucasian 94 145 DSM-III-R Tunisian 44 44 Wei et al (1995) C o n Wrmed by SAGB b United Kingdom 176 107 Jonsson et al (1996) DSM-III-R Caucasian 118 78 Burgert et al (1998) DSM the distribution of the alleles and genotypes among diVerent populations, such as the TH10 and TH9 alleles, suggesting that the polymorphism might be population-speciWc. It is noteworthy that for TH the Wrst published study reporting association of the genetic variant with schizophrenia may be a poor predictor of subsequent results (Table 1).…”

Section: Authormentioning

confidence: 99%

Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia

2006

Hum Genet

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A number of studies have suggested an association between schizophrenia and the tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) genes. On the other hand, several studies attempting to replicate these findings have produced mixed results, possibly reflecting inadequate statistical power of the individual studies as well as the heterogeneity inherent in schizophrenia. In an attempt to clarify this inconsistency our meta-analysis has combined all the studies using multiple research methods published up to February 2006 to give a comprehensive picture of the role of three hydroxylase-related genes. The TPH A218C/A779C (OR = 1.18, 95% C.I. 1.06-1.33, P = 0.004) revealed a significant association with schizophrenia. However, the evidence for the TH and phenylalanine hydroxylase (PAH) genes was weak. No publication bias was detected in current studies. The findings, which may implicate the involvement of TPH in the pathogenesis of schizophrenia, have potentially important clinical, scientific and public health implications as well as providing a putative basis for the study of hydroxylase-related drugs. To our knowledge, this is the first meta-analysis of association between the three genes and schizophrenia.

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“…The altered activity of TPH is thought to dysregulate the 5-HT pathway and is implicated in the etiology of schizophrenia (Sekizawa et al 2004;Zaboli et al 2006). At the molecular level, TPH is encoded by two genes: TPH1 and TPH2.…”

Section: Introductionmentioning

confidence: 99%

Association Study of Tryptophan Hydroxylase-2 Gene in Schizophrenia and Its Clinical Features in Chinese Han Population

Zhang

Shao

et al. 2010

J Mol Neurosci

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Schizophrenia is a chronic and severe mental illness which is characterized by the development of various detrimental clinical features, and its etiology still remains unknown. Based on the evidence from neurobiological and pharmacological research, dysfunctions in central serotonergic transmission may be involved in the development of schizophrenia. Tryptophan hydroxylase 2 (TPH2), a newly identified isoform of tryptophan hydroxylase (the rate limiting enzyme in the biosynthesis of serotonin), regulates the brain-specific serotonin synthesis. To further clarify the role of TPH2 in this disease, we performed a case-control study to examine the association of the TPH2 gene with schizophrenia and its clinical features. We genotyped three putative functional polymorphisms (rs4570625, rs7305115, and rs4290270) within the gene and carried out a case-control study consisting of 304 schizophrenia patients and 362 healthy subjects. The severity of psychotic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). The frequencies of genotypes and alleles of rs4570625, rs7305115, and rs4290270 did not differ significantly between schizophrenic patients and controls. However, the PANSS positive symptom subcore was significantly associated with rs4570625 (P=0.022). These results suggest that rs4570625 of TPH2 may play an important role in the development of positive symptoms in Han Chinese schizophrenic patients.

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Childhood‐onset schizophrenia and tryptophan hydroxylase gene polymorphism

Cited by 13 publications

References 13 publications

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Meta-analysis shows association between the tryptophan hydroxylase (TPH) gene and schizophrenia

Association Study of Tryptophan Hydroxylase-2 Gene in Schizophrenia and Its Clinical Features in Chinese Han Population

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