Serotonin transporter gene polymorphism modulates activity and connectivity within an emotional arousal network of healthy men during an aversive visceral stimulus

Lisa A. Kilpatrick, Emeran A. Mayer, Jennifer S. Labus, Arpana Gupta, Toyohiro Hamaguchi, Tomoko Mizuno, Hazuki Komuro, Michiko Kano, Motoyori Kanazawa, Masashi Aoki, Shin Fukudo

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background and Aims: The 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) has been linked to increased stress responsiveness and negative emotional states. During fearful face recognition individuals with the s allele of 5-HTTLPR show greater amygdala activation. We aimed to test the hypothesis that the 5-HTTLPR polymorphism differentially affects connectivity within brain networks during an aversive visceral stimulus. Methods: Twenty-three healthy male subjects were enrolled. DNA was extracted from the peripheral blood. The genotype of 5-HTTLPR was determined using polymerase chain reaction. Subjects with the s/s genotype (n = 13) were compared to those with the l allele (genotypes l/s, l/l, n = 10). Controlled rectal distension from 0 to 40 mmHg was delivered in random order using a barostat. Radioactive H2[15-O] saline was injected at time of distension followed by positron emission tomography (PET). Changes in regional cerebral blood flow (rCBF) were analyzed using partial least squares (PLS) and structural equation modeling (SEM). Results: During baseline, subjects with s/s genotype demonstrated a significantly increased negative influence of pregenual ACC (pACC) on amygdala activity compared to l-carriers. During inflation, subjects with s/s genotype demonstrated a significantly greater positive influence of hippocampus on amygdala activity compared to l-carriers. Conclusion: In male Japanese subjects, individuals with s/s genotype show alterations in the connectivity of brain regions involved in stress responsiveness and emotion regulation during aversive visceral stimuli compared to those with l carriers.

Original languageEnglish
Article numbere0123183
JournalPloS one
Volume10
Issue number4
DOIs
Publication statusPublished - 2015 Apr 20

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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