@article{KlaukeWinterGajewskaetal.2012,
  author    = {Klauke, Benedikt and Winter, Bernward and Gajewska, Agnes and Zwanzger, Peter and Reif, Andreas and Herrmann, Martin J. and Dlugos, Andrea and Warrings, Bodo and Jacob, Christian and M{\"u}hlberger, Andreas and Arolt, Volker and Pauli, Paul and Deckert, J{\"u}rgen and Domschke, Katharina},
  title     = {Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {6},
  doi       = {10.1371/journal.pone.0039709},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132184},
  pages     = {e39709},
  year      = {2012},
  abstract  = {The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.},
  language  = {en}
}
@article{PauliGlotzbachSchoonAndreattaetal.2013,
  author    = {Pauli, Paul and Glotzbach-Schoon, Evelyn and Andreatta, Marta and Reif, Andreas and Ewald, Heike and Tr{\"o}ger, Christian and Baumann, Christian and Deckert, J{\"u}rgen and M{\"u}hlberger, Andreas},
  title     = {Contextual fear conditioning in virtual reality is affected by 5HTTLPR and NPSR1 polymorphisms: effects on fear-potentiated startle},
  series = {Frontiers in Behavioral Neuroscience},
  journal   = {Frontiers in Behavioral Neuroscience},
  doi       = {10.3389/fnbeh.2013.00031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96516},
  year      = {2013},
  abstract  = {The serotonin (5-HT) and neuropeptide S (NPS) systems are discussed as important genetic modulators of fear and sustained anxiety contributing to the etiology of anxiety disorders. Sustained anxiety is a crucial characteristic of most anxiety disorders which likely develops through contextual fear conditioning. This study investigated if and how genetic alterations of the 5-HT and the NPS systems as well as their interaction modulate contextual fear conditioning; specifically, function polymorphic variants in the genes coding for the 5-HT transporter (5HTT) and the NPS receptor (NPSR1) were studied. A large group of healthy volunteers was therefore stratified for 5HTTLPR (S+ vs. LL carriers) and NPSR1 rs324981 (T+ vs. AA carriers) polymorphisms resulting in four genotype groups (S+/T+, S+/AA, LL/T+, LL/AA) of 20 participants each. All participants underwent contextual fear conditioning and extinction using a virtual reality (VR) paradigm. During acquisition, one virtual office room (anxiety context, CXT+) was paired with an unpredictable electric stimulus (unconditioned stimulus, US), whereas another virtual office room was not paired with any US (safety context, CXT-). During extinction no US was administered. Anxiety responses were quantified by fear-potentiated startle and ratings. Most importantly, we found a gene × gene interaction on fear-potentiated startle. Only carriers of both risk alleles (S+/T+) exhibited higher startle responses in CXT+ compared to CXT-. In contrast, anxiety ratings were only influenced by the NPSR1 polymorphism with AA carriers showing higher anxiety ratings in CXT+ as compared to CXT-. Our results speak in favor of a two level account of fear conditioning with diverging effects on implicit vs. explicit fear responses. Enhanced contextual fear conditioning as reflected in potentiated startle responses may be an endophenotype for anxiety disorders.},
  language  = {en}
}