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@ARTICLE{Hohoff:893314,
      author       = {Hohoff, Christa and Kroll, Tina and Zhao, Baoyuan and
                      Kerkenberg, Nicole and Lang, Ilona and Schwarte, Kathrin and
                      Elmenhorst, David and Elmenhorst, Eva-Maria and Aeschbach,
                      Daniel and Zhang, Weiqi and Baune, Bernhard T. and Neumaier,
                      Bernd and Bauer, Andreas and Deckert, Jürgen},
      title        = {{ADORA}2{A} variation and adenosine {A}1 receptor
                      availability in the human brain with a focus on
                      anxiety-related brain regions: modulation by {ADORA}1
                      variation},
      journal      = {Translational Psychiatry},
      volume       = {10},
      number       = {1},
      issn         = {2158-3188},
      address      = {London},
      publisher    = {Nature Publishing Group},
      reportid     = {FZJ-2021-02688},
      pages        = {406},
      year         = {2020},
      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.},
      cin          = {INM-5 / INM-2},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-5-20090406 / I:(DE-Juel1)INM-2-20090406},
      pnm          = {573 - Neuroimaging (POF3-573)},
      pid          = {G:(DE-HGF)POF3-573},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {33235193},
      UT           = {WOS:000596251600001},
      doi          = {10.1038/s41398-020-01085-w},
      url          = {https://juser.fz-juelich.de/record/893314},
}