Manuel Mattheisen

The 5-HTTLPR polymorphism affects network-based functional connectivity in the visual-limbic system in healthy adults

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Hengyi Cao, University Medical Centre Mannheim, University Hospital Bonn
  • ,
  • Anais Harneit, University Medical Centre Mannheim, University Hospital Bonn
  • ,
  • Henrik Walter, Charite - Universitatsmedizin Berlin, University Hospital Bonn
  • ,
  • Susanne Erk, Charite - Universitatsmedizin Berlin
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  • Urs Braun, University Medical Centre Mannheim
  • ,
  • Carolin Moessnang, University Medical Centre Mannheim
  • ,
  • Lena S. Geiger, University Medical Centre Mannheim
  • ,
  • Zhenxiang Zang, University Medical Centre Mannheim
  • ,
  • Sebastian Mohnke, Charite - Universitatsmedizin Berlin
  • ,
  • Andreas Heinz, Charite - Universitatsmedizin Berlin
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  • Nina Romanczuk-Seiferth, Charite - Universitatsmedizin Berlin
  • ,
  • Thomas Mühleisen, Forschungszentrum Jülich (FZJ), University Hospital and University of Basel
  • ,
  • Manuel Mattheisen
  • Stephanie H. Witt, University Medical Centre Mannheim
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  • Sven Cichon, Forschungszentrum Jülich (FZJ), University Hospital and University of Basel, University of Bonn, University of Basel
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  • Markus M. Nöthen, University of Bonn, University Hospital Bonn
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  • Marcella Rietschel, University Medical Centre Mannheim
  • ,
  • Andreas Meyer-Lindenberg, University Medical Centre Mannheim, University Hospital Bonn
  • ,
  • Heike Tost, University Medical Centre Mannheim, University Hospital Bonn

The serotonin transporter-linked polymorphic region 5-HTTLPR is a key genetic regulator of 5-HTT expression in the human brain where the short allele S has been implicated in emotion dysregulation. However, the neural mechanism underlying the association between this variant and emotion processing is still unclear. Earlier studies suggested an effect of 5-HTTLPR on amygdala activation during emotional face processing. However, this association has been questioned in recent studies employing larger sample sizes and meta-analyses. Here, we examined a sample of 223 healthy subjects with a well-established fMRI emotional face processing task to (1) re-evaluate the association between 5-HTTLPR and amygdala activation, (2) explore potential network-based functional connectivity phenotypes for associations with 5-HTTLPR, and (3) probe the reliability, behavioral significance and potential structural confounds of the identified network phenotype. Our results revealed no significant effect of 5-HTTLPR on amygdala activation (P40.79). However, the number of S alleles was significantly correlated with functional connectivity of a visual-limbic subnetwork (PFWE= 0.03). The subnetwork cluster included brain regions that are pivotal to emotion regulation such as the hippocampus, orbitofrontal cortex, anterior cingulate gyrus, fusiform gyrus, and subcortex. Notably, individuals with lower subnetwork connectivity had significantly higher emotion suppression scores (P= 0.01). Further, the connectivity metrics were test-retest reliable and independent from subnetwork gray matter volume and white matter anisotropy. Our data provide evidence for a functional network-based phenotype linking genetic variation in 5-HTTLPR to emotion regulation, and suggest that further critical evaluations of the association between 5-HTTLPR and amygdala activation are warranted.

Original languageEnglish
JournalNeuropsychopharmacology
Volume43
Issue2
Pages (from-to)406-414
Number of pages9
ISSN0893-133X
DOIs
Publication statusPublished - 2018

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