title: Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress.
abstract: OBJECTIVE
  Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress.
  
  
  METHODS
  An acute laboratory stressor was administered to 51 healthy women during blood-oxygen-level-dependent functional magnetic resonance imaging. In this task, participants were threatened with electric shocks of uncertain intensity, which were unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration.
  
  
  RESULTS
  Relative to women carrying the L allele, those with the SS genotype showed enhanced activation during threat anticipation in a network of regions, including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas enhanced negative coupling between insula activation and perceived success at regulating anxiety was observed in individuals carrying the L allele.
  
  
  CONCLUSIONS
  These findings suggest that during stress exposure, neural systems that enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat may be engaged preferentially in individuals with the SS genotype. This may be one mechanism underlying the risk for psychopathology conferred by the S allele upon exposure to life stressors.
authors.affiliation: Department of Psychology, Stanford University, Stanford, California, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Drabant
authors.forename: Wiveka
authors.initials: W
authors.lastname: Ramel
authors.forename: Michael D
authors.initials: MD
authors.lastname: Edge
authors.forename: Luke W
authors.initials: LW
authors.lastname: Hyde
authors.forename: Janice R
authors.initials: JR
authors.lastname: Kuo
authors.forename: Philippe R
authors.initials: PR
authors.lastname: Goldin
authors.forename: Ahmad R
authors.initials: AR
authors.lastname: Hariri
authors.forename: James J
authors.initials: JJ
authors.lastname: Gross
mesh_terms: D000328:Adult; D000483:Alleles; D001921:Brain / Q000503:physiopathology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology*; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology*; D009434:Neural Pathways / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology*
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins