title: The association between the 5-HTTLPR and neural correlates of fear conditioning and connectivity.
abstract: Strong evidence links the 5-HTTLPR genotype to the modulation of amygdala reactivity during fear conditioning, which is considered to convey the increased vulnerability for anxiety disorders in s-allele carriers. In addition to amygdala reactivity, the 5-HTTLPR has been shown to be related to alterations in structural and effective connectivity. The aim of this study was to investigate the effects of 5-HTTLPR genotype on amygdala reactivity and effective connectivity during fear conditioning, as well as structural connectivity [as measured by diffusion tensor imaging (DTI)]. To integrate different classification strategies, we used the bi-allelic (s-allele vs l/l-allele group) as well as the tri-allelic (low-functioning vs high-functioning) classification approach. S-allele carriers showed exaggerated amygdala reactivity and elevated amygdala-insula coupling during fear conditioning (CS + > CS-) compared with the l/l-allele group. In addition, DTI analysis showed increased fractional anisotropy values in s-allele carriers within the uncinate fasciculus. Using the tri-allelic classification approach, increased amygdala reactivity and amygdala insula coupling were observed in the low-functioning compared with the high-functioning group. No significant differences between the two groups were found in structural connectivity. The present results add to the current debate on the influence of the 5-HTTLPR on brain functioning. These differences between s-allele and l/l-allele carriers may contribute to altered vulnerability for psychiatric disorders.
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany tim.klucken@psychol.uni-giessen.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Klucken
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Schweckendiek
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Blecker
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Bertram
authors.initials: B
authors.lastname: Walter
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kuepper
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Hennig
authors.affiliation: Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany Department of Psychotherapy and Systems Neuroscience, Bender Institute of Neuroimaging, and Department of Personality Psychology and Individual Differences, Justus Liebig University Giessen, Giessen, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stark
mesh_terms: D000483:Alleles; D000679:Amygdala / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D004644:Emotions / Q000502:physiology; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D019580:Perforant Pathway / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology*; D066127:White Matter / Q000502:physiology; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: 5-HTTLPR genotype; amygdala; classical conditioning; emotion; fear