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Abstracts
  • Klucken, T., Wehrum, S., Schweckendiek, J., Merz, C. J., Hennig, J., Vaitl, D., & Stark, R. (2013). The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning. Human Brain Mapping, 34(10), 2549–2560. https://doi.org/10.1002/hbm.22085

    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. CONCLUSION: 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.

  • Klucken, T., Alexander, N., Schweckendiek, J., Merz, C. J., Kagerer, S., Osinsky, R., Walter, B., Vaitl, D., Hennig, J., & Stark, R. (2013). Individual differences in neural correlates of fear conditioning as a function of 5-HTTLPR and stressful life events. Social Cognitive and Affective Neuroscience, 8(3), 318–325. https://doi.org/10.1093/scan/nss005

    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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