Associations between prefrontal γ-aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women

Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects...

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Published inThe international journal of neuropsychopharmacology Vol. 16; no. 8; pp. 1707 - 1717
Main Authors Preuss, Nora, Salehi, Basira, van der Veen, Jan Willem, Shen, Jun, Drevets, Wayne C., Hodgkinson, Colin, Goldman, David, Hasler, Gregor
Format Journal Article
LanguageEnglish
Published Cambridge, UK Cambridge University Press 01.09.2013
Oxford University Press
Subjects
Adult
Alleles
Anxiety
Depressive Disorder, Major - genetics
Depressive Disorder, Major - pathology
Female
gamma-Aminobutyric Acid - metabolism
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Linkage Disequilibrium
Magnetic Resonance Spectroscopy
Male
Middle Aged
Panic attacks
Panic Disorder - genetics
Panic Disorder - pathology
Polymorphism, Single Nucleotide - genetics
Prefrontal Cortex - metabolism
Psychiatric Status Rating Scales
RNA, Messenger - metabolism
Sex Characteristics
Tryptophan Hydroxylase - genetics
Young Adult
GABA
magnetic resonance spectroscopy
genetics
tryptophan hydroxylase 2
single nucleotide polymorphisms
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Abstract Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (−703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (−703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (−703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
AbstractList Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (−703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (−703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (−703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (-703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (-703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (−703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (−703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (−703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Interactions between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 ( TPH2 ) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (–703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of 2 TPH2 SNPs, namely, rs4570625 (of –703 G/T) and rs2129575 (p ≤ 0.0004) and the C-allele frequency of 1 TPH2 SNP, namely, rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (–703 G/T), rs2129575, and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Associations between the central serotonergic and gamma -aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575 (p0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (-703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and cognition and in the pathophysiology and pharmacotherapy of highly prevalent psychiatric disorders. The goal of this study was to test the effects of common variants of the tryptophan hydroxylase isoform 2 (TPH2) gene on GABA concentration in the prefrontal cortex (PFC) using magnetic resonance spectroscopy. In this study involving 64 individuals, we examined the associations between prefrontal cortical GABA concentration and 12 single nucleotide polymorphisms (SNPs) spanning the TPH2 gene, including rs4570625 (-703 G/T SNP), a potentially functional TPH2 polymorphism that has been associated with decreased TPH2 mRNA expression and panic disorder. Our results revealed a significant association between increased GABA concentration in the PFC and the T-allele frequencies of two TPH2 SNPs, namely rs4570625 (-703 G/T) and rs2129575 (p⩽0.0004) and the C-allele frequency of one TPH2 SNP, namely rs1386491 (p = 0.0003) in female subjects. We concluded that rs4570625 (-703 G/T), rs2129575 and rs1386491 play a significant role in GABAergic neurotransmission and may contribute to the sex-specific dysfunction of the GABAergic system in the PFC.
Author Shen, Jun
van der Veen, Jan Willem
Hasler, Gregor
Salehi, Basira
Preuss, Nora
Hodgkinson, Colin
Drevets, Wayne C.
Goldman, David
AuthorAffiliation 1 Department of Psychology, University of Bern, 3012 Berne, Switzerland
5 Laureate Institute for Brain Research, and University of Oklahoma College of Medicine, 6655 S. Yale Ave., Tulsa, OK 74136, USA
7 Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism (NIAAA)
4 Department of Psychiatry, Yale School of Medicine, 300 George St New Haven, CT 06511, USA
3 National Institute of Mental Health, Magnetic Resonance Spectroscopy Core, Bldg. 10, Rm. 2D51A 9000 Rockville Pike, MSC 1527, Bethesda, MD 20892-1527, USA
6 Janssen Research & Development, LLC, of Johnson & Johnson, Inc., Titusville, NJ, 08560
2 Psychiatric University Hospital, University of Bern, 3000 Berne 60, Switzerland
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DocumentTitleAlternate Association between TPH2 gene and prefrontal GABA
N. Preuss et al.
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Keywords GABA
magnetic resonance spectroscopy
genetics
tryptophan hydroxylase 2
single nucleotide polymorphisms
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PublicationDate 2013-09-01
PublicationDateYYYYMMDD 2013-09-01
PublicationDate_xml – month: 09
  year: 2013
  text: 2013-09-01
  day: 01
PublicationDecade 2010
PublicationPlace Cambridge, UK
PublicationPlace_xml – name: Cambridge, UK
– name: England
– name: Oxford
PublicationTitle The international journal of neuropsychopharmacology
PublicationTitleAlternate Int. J. Neuropsychopharm
PublicationYear 2013
Publisher Cambridge University Press
Oxford University Press
Publisher_xml – name: Cambridge University Press
– name: Oxford University Press
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Snippet Associations between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and...
Associations between the central serotonergic and gamma -aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and...
Interactions between the central serotonergic and γ-aminobutyric acid (GABA) systems play key roles in the prefrontal cortical regulation of emotion and...
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cambridge
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StartPage 1707
SubjectTerms Adult
Alleles
Anxiety
Depressive Disorder, Major - genetics
Depressive Disorder, Major - pathology
Female
gamma-Aminobutyric Acid - metabolism
Genetic Association Studies
Genetic Predisposition to Disease
Genotype
Humans
Linkage Disequilibrium
Magnetic Resonance Spectroscopy
Male
Middle Aged
Panic attacks
Panic Disorder - genetics
Panic Disorder - pathology
Polymorphism, Single Nucleotide - genetics
Prefrontal Cortex - metabolism
Psychiatric Status Rating Scales
RNA, Messenger - metabolism
Sex Characteristics
Tryptophan Hydroxylase - genetics
Young Adult
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Title Associations between prefrontal γ-aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women
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https://www.ncbi.nlm.nih.gov/pubmed/23552096
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