title: Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events.
abstract: Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS(+)) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S' allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs demonstrated elevated reactivity to the CS(+) in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.
authors.affiliation: Bender Institute of Neuroimaging, Justus Liebig University Giessen, Otto-Behaghel-Strasse 10 H, Giessen, Germany Tim.Klucken@psychol.uni-giessen.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Klucken
authors.forename: Nina
authors.initials: N
authors.lastname: Alexander
authors.forename: Jan
authors.initials: J
authors.lastname: Schweckendiek
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Merz
authors.forename: Sabine
authors.initials: S
authors.lastname: Kagerer
authors.forename: Roman
authors.initials: R
authors.lastname: Osinsky
authors.forename: Bertram
authors.initials: B
authors.lastname: Walter
authors.forename: Dieter
authors.initials: D
authors.lastname: Vaitl
authors.forename: Juergen
authors.initials: J
authors.lastname: Hennig
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stark
mesh_terms: D000328:Adult; D001921:Brain / Q000098:blood supply / Q000473:pathology; D001931:Brain Mapping; D003214:Conditioning, Classical / Q000502:physiology*; D004252:DNA Mutational Analysis; D005239:Fear / Q000523:psychology*; D005260:Female; D005712:Galvanic Skin Response / Q000235:genetics; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007206:Individuality; D008016:Life Change Events; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D013315:Stress, Psychological / Q000235:genetics / Q000473:pathology / Q000523:psychology; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D010100:Oxygen