title: Serotonin Transporter Gene Polymorphism Modulates Activity and Connectivity within an Emotional Arousal Network of Healthy Men during an Aversive Visceral Stimulus.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, California, United States of America.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Kilpatrick
authors.affiliation: Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, California, United States of America.
authors.forename: Emeran A
authors.initials: EA
authors.lastname: Mayer
authors.affiliation: Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, California, United States of America.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Labus
authors.affiliation: Oppenheimer Family Center for Neurobiology of Stress, Division of Digestive Diseases, David Geffen School of Medicine at University of California at Los Angeles (UCLA), Los Angeles, California, United States of America.
authors.forename: Arpana
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Toyohiro
authors.initials: T
authors.lastname: Hamaguchi
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Mizuno
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Komuro
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Kano
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Psychosomatic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Motoyori
authors.initials: M
authors.lastname: Kanazawa
authors.affiliation: Department of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Aoki
authors.affiliation: Department of Behavioral Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Psychosomatic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Fukudo
mesh_terms: D000328:Adult; D001143:Arousal; D004644:Emotions; D060005:Genotyping Techniques; D006262:Health; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D010812:Physical Stimulation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D014781:Viscera / Q000502:physiology*; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins