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

Preuss, Nora; Salehi, Basira; van der Veen, Jan Willem; Shen, Jun; Drevets, Wayne C.; Hodgkinson, Colin; Goldman, David; Hasler, Gregor (2013). Associations between prefrontal γ-aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women. International journal of neuropsychopharmacology, 16(8), pp. 1707-1717. Cambridge University Press 10.1017/S1461145713000254

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Psychiatry and Psychotherapy > Healthcare Research
07 Faculty of Human Sciences > Institute of Psychology > Cognitive Psychology, Perception and Methodology

UniBE Contributor:

Preuss, Nora; Salehi, Basira and Hasler, Gregor

Subjects:

100 Philosophy > 150 Psychology
600 Technology > 610 Medicine & health

ISSN:

1461-1457

Publisher:

Cambridge University Press

Language:

English

Submitter:

Daniela Zurkinden

Date Deposited:

03 Apr 2014 11:20

Last Modified:

09 Aug 2016 14:31

Publisher DOI:

10.1017/S1461145713000254

PubMed ID:

23552096

BORIS DOI:

10.7892/boris.46043

URI:

https://boris.unibe.ch/id/eprint/46043

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