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ADORA2A variation and adenosine A 1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation

Hohoff, C. and Kroll, T. and Zhao, B. and Kerkenberg, N. and Lang, I. and Schwarte, K. and Elmenhorst, D. and Elmenhorst, E.-M. and Aeschbach, D. and Zhang, W. and Baune, B.T. and Neumaier, B. and Bauer, A. and Deckert, J. (2020) ADORA2A variation and adenosine A 1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation. Translational Psychiatry, 10 (1), p. 406. Springer Nature. doi: 10.1038/s41398-020-01085-w. ISSN 2158-3188.

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Official URL: https://www.nature.com/articles/s41398-020-01085-w

Abstract

Adenosine, its interacting A1 and A2A receptors, and particularly the variant rs5751876 in the A2A gene ADORA2A have been shown to modulate anxiety, arousal, and sleep. In a pilot positron emission tomography (PET) study in healthy male subjects, we suggested an effect of rs5751876 on in vivo brain A1 receptor (A1AR) availability. As female sex and adenosinergic/dopaminergic interaction partners might have an impact on this rs5751876 effect on A1AR availability, we aimed to (1) further investigate the pilot male-based findings in an independent, newly recruited cohort including women and (2) analyze potential modulation of this rs5751876 effect by additional adenosinergic/dopaminergic gene variation. Healthy volunteers (32/11 males/females) underwent phenotypic characterization including self-reported sleep and A1AR-specific quantitative PET. Rs5751876 and 31 gene variants of adenosine A1, A2A, A2B, and A3 receptors, adenosine deaminase, and dopamine D2 receptor were genotyped. Multivariate analysis revealed an rs5751876 effect on A1AR availability (P = 0.047), post hoc confirmed in 30 of 31 brain regions (false discovery rate (FDR) corrected P values < 0.05), but statistically stronger in anxiety-related regions (e.g., amygdala, hippocampus). Additional effects of ADORA1 rs1874142 were identified; under its influence rs5751876 and rs5751876 × sleep had strengthened effects on A1AR availability (Pboth < 0.02; post hoc FDR-corrected Ps < 0.05 for 29/30 regions, respectively). Our results support the relationship between rs5751876 and A1AR availability. Additional impact of rs1874142, together with rs5751876 and sleep, might be involved in regulating arousal and thus the development of mental disorders like anxiety disorders. The interplay of further detected suggestive ADORA2A × DRD2 interaction, however, necessitates larger future samples more comparable to magnetic resonance imaging (MRI)-based samples.

Item URL in elib:https://elib.dlr.de/140168/
Document Type:Article
Title:ADORA2A variation and adenosine A 1 receptor availability in the human brain with a focus on anxiety-related brain regions: modulation by ADORA1 variation
Authors:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Hohoff, C.UNSPECIFIEDUNSPECIFIED
Kroll, T.UNSPECIFIEDUNSPECIFIED
Zhao, B.UNSPECIFIEDUNSPECIFIED
Kerkenberg, N.UNSPECIFIEDUNSPECIFIED
Lang, I.UNSPECIFIEDUNSPECIFIED
Schwarte, K.UNSPECIFIEDUNSPECIFIED
Elmenhorst, D.UNSPECIFIEDUNSPECIFIED
Elmenhorst, E.-M.Eva-Maria.Elmenhorst (at) dlr.dehttps://orcid.org/0000-0003-0336-6705
Aeschbach, D.daniel.aeschbach (at) dlr.deUNSPECIFIED
Zhang, W.UNSPECIFIEDUNSPECIFIED
Baune, B.T.UNSPECIFIEDUNSPECIFIED
Neumaier, B.UNSPECIFIEDUNSPECIFIED
Bauer, A.UNSPECIFIEDUNSPECIFIED
Deckert, J.UNSPECIFIEDUNSPECIFIED
Date:24 November 2020
Journal or Publication Title:Translational Psychiatry
Refereed publication:Yes
Open Access:Yes
Gold Open Access:Yes
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:10
DOI :10.1038/s41398-020-01085-w
Page Range:p. 406
Publisher:Springer Nature
ISSN:2158-3188
Status:Published
Keywords:adenosine, anxiety, polymorphisms, arousal
HGF - Research field:Aeronautics, Space and Transport
HGF - Program:Space
HGF - Program Themes:Research under Space Conditions
DLR - Research area:Raumfahrt
DLR - Program:R FR - Research under Space Conditions
DLR - Research theme (Project):R - Projekt :envihab (old)
Location: Köln-Porz
Institutes and Institutions:Institute of Aerospace Medicine > Sleep and Human Factors Research
Deposited By: Sender, Alina
Deposited On:12 Jan 2021 11:21
Last Modified:14 Jan 2021 13:57

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