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  Region specific metabolic correlates contribute to gene and sex relationship of anxiety endophenotypes

Colic, L., Li, M., Demenscu, L., Li, S., Muller, I., Richter, A., et al. (2017). Region specific metabolic correlates contribute to gene and sex relationship of anxiety endophenotypes. Journal of Neural Transmission, 124(10), 21-21.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-C54A-F Version Permalink: http://hdl.handle.net/21.11116/0000-0001-0113-8
Genre: Meeting Abstract

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 Creators:
Colic, L, Author
Li, M, Author
Demenscu, LR, Author
Li, S, Author
Muller, I, Author
Richter, A, Author
Seidenbecher, C, Author
Speck, O, Author
Schott, B, Author
Stork, O, Author
Walter, M1, Author              
Affiliations:
1Universität Tübingen, ou_persistent22              

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 Abstract: Objective: Anxiety disorders are typically prevalent in women, but the factors contributing to sex bias are unknown. Investigations have emphasized the role of the cortico–limbic circuit including the anterior cingulate cortex (ACC) in anxiety disorders. Pregenual ACC (pgACC) was highlighted as key region for successful affect regulation, and dysregulation of transmitter balance (GABA/Glu) was reported in anxiety disorders in this region. We therefore investigated whether a SNP in GABA synthesizing enzyme GAD65 and sex are associated with inhibitory/excitatory balance in ACC regions (pgACC and aMCC). Additionally, we explored the relationship between GAD65, sex, metabolites and harm avoidance (HA). Methods: 107 healthy subjects (45 females, age = 27.07 ± 6.75) underwent a magnetic resonance spectroscopy in 7T. GABA and Glu levels were measured in aMCC and pgACC. Subjects completed TCI questionnaire and were genotyped for GAD65 promoter (40 G-carriers). Region by genotype by sex ANOVA was done including age as confound for GABA/Glu levels. Likewise, we tested differences for HA, and association to pgACC metabolism. Lastly, we performed an analysis of mediating effects of GABA/Glu on GAD65 to HA, moderated by sex. Results: We found an interaction effect on GABA/Glu (F1,63 = 8.69, p = 0.004). Post-hoc analysis revealed that this interaction was driven by genotype difference in females in pgACC (t(37) = –2.27, p = 0.029). There was an effect of sex on HA and pgACC GABA/Glu levels (women: ρ(25) = –0.552, p = 0.003; men: ρ(31) = –0.003, p = 0.98). We also observed an effect for the moderated mediation (−1.17, −0.056). Conclusion: Our results show that GABAergic gene polymorphisms and sex are factors contributing to anxiety endophenotypes in women via metabolic correlates in the pgACC. This interaction could be relevant for the observed sex bias in prevalence of anxiety disorders and possible sex specific treatment strategies.

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 Dates: 2017-10
 Publication Status: Published in print
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 Identifiers: DOI: 10.1007/s00702-017-1777-9
BibTex Citekey: ColicLDLMRSSSSW2017
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Title: WASAD Congress 2017: Anxiety and Stress -Translational Perspectives
Place of Event: Würzburg, Germany
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Title: Journal of Neural Transmission
Source Genre: Journal
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Pages: - Volume / Issue: 124 (10) Sequence Number: - Start / End Page: 21 - 21 Identifier: -