Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events |
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Authors: | Tim Klucken Nina Alexander Jan Schweckendiek Christian J Merz Sabine Kagerer Roman Osinsky Bertram Walter Dieter Vaitl Juergen Hennig Rudolf Stark |
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Institution: | 1.Bender Institute of Neuroimaging, Justus Liebig University Giessen, 35394 Giessen, 2.Department of Biological Psychology, Technical University of Dresden, 01069 Dresden, 3.Department of Cognitive Psychology, Ruhr-University Bochum, 44780 Bochum, 4.Department of Psychology I, University of Wuerzburg, 97070 Würzburg and 5.Department of Psychobiology and Behavioral Medicine, Justus Liebig University Giessen, 35394 Giessen |
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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. |
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Keywords: | imaging genetics classical conditioning fear 5-HTTLPR amygdala |
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