title: The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning.
abstract: BACKGROUND
  Current models suggest that a variation in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with altered amygdala reactivity not only towards negative but also towards positive stimuli, which has been neglected in the past. This association may possibly convey an elevated vulnerability for psychopathology like abuse, craving, and relapses. Since appetitive conditioning is a crucial mechanism in the pathogenesis of these psychiatric disorders, the identification of specific factors contributing to interindividual variation is important.
  
  
  METHODS
  In the present study (N = 86), an appetitive conditioning paradigm was conducted, in which a neutral stimulus (CS+) was associated with appetitive stimuli, while a second stimulus (CS-) predicted their absence. Subjects were genotyped according to the 5-HTTLPR genotype.
  
  
  RESULTS
  As the main result, we report a significant association between the 5-HTTLPR genotype and hemodynamic responses. Individuals with the s-allele displayed elevated conditioned bilateral amygdala activity in contrast to l/l-allele carriers. Further, increased hemodynamic responses in s-allele carriers were also found in the extended emotional network including the orbitofrontal cortex, the thalamus, and the ventral striatum.
  
  
  CONCLUSIONS
  The present findings indicate an association of the 5-HTTLPR and altered conditioned responses in appetitive conditioning. Further, the findings contribute to the ongoing debate on 5-HTTLPR dependent hemodynamic response patterns by emphasizing that s-allele carriers are not exclusively biased towards fearful, but also towards positive stimuli. In conclusion, our results imply that s-allele carriers might be better described as hyper-reactive towards salient stimuli, which may convey vulnerability for the development of psychiatric disorders.
authors.affiliation: Bender Institute of Neuroimaging, Justus Liebig University Giessen, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Klucken
authors.forename: Sina
authors.initials: S
authors.lastname: Wehrum
authors.forename: Jan
authors.initials: J
authors.lastname: Schweckendiek
authors.forename: Christian Josef
authors.initials: CJ
authors.lastname: Merz
authors.forename: Juergen
authors.initials: J
authors.lastname: Hennig
authors.forename: Dieter
authors.initials: D
authors.lastname: Vaitl
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stark
mesh_terms: D000328:Adult; D000483:Alleles; D000679:Amygdala / Q000502:physiology; D001070:Appetitive Behavior / Q000502:physiology*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000502:physiology; D002560:Cerebrovascular Circulation; D003216:Conditioning, Operant / Q000502:physiology; D003342:Corpus Striatum / Q000502:physiology; D017352:Echo-Planar Imaging; D004882:Erotica; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D005712:Galvanic Skin Response; D005838:Genotype; D006179:Gyrus Cinguli / Q000502:physiology; D006439:Hemodynamics; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000502:physiology*; D012725:Sexual Behavior / Q000502:physiology*; D013788:Thalamus / Q000502:physiology; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins