@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{ConzelmannReifJacobetal.2012, author = {Conzelmann, Annette and Reif, Andreas and Jacob, Christian and Weyers, Peter and Lesch, Klaus-Peter and Lutz, Beat and Pauli, Paul}, title = {A polymorphism in the gene of the endocannabinoid-degrading enzyme FAAH (FAAH C385A) is associated with emotional-motivational reactivity}, series = {Psychopharmacology}, volume = {224}, journal = {Psychopharmacology}, number = {4}, doi = {10.1007/s00213-012-2785-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126845}, pages = {573-579}, year = {2012}, abstract = {RATIONALE: The endocannabinoid (eCB) system is implicated in several psychiatric disorders. Investigating emotional-motivational dysfunctions as underlying mechanisms, a study in humans revealed that in the C385A polymorphism of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the eCB anandamide (AEA), A carriers, who are characterized by increased signaling of AEA as compared to C/C carriers, exhibited reduced brain reactivity towards unpleasant faces and enhanced reactivity towards reward. However, the association of eCB system with emotional-motivational reactivity is complex and bidirectional due to upcoming compensatory processes. OBJECTIVES: Therefore, we further investigated the relationship of the FAAH polymorphism and emotional-motivational reactivity in humans. METHODS: We assessed the affect-modulated startle, and ratings of valence and arousal in response to higher arousing pleasant, neutral, and unpleasant pictures in 67 FAAH C385A C/C carriers and 45 A carriers. RESULTS: Contrarily to the previous functional MRI study, A carriers compared to C/C carriers exhibited an increased startle potentiation and therefore emotional responsiveness towards unpleasant picture stimuli and reduced startle inhibition indicating reduced emotional reactivity in response to pleasant pictures, while both groups did not differ in ratings of arousal and valence. CONCLUSIONS: Our findings emphasize the bidirectionality and thorough examination of the eCB system's impact on emotional reactivity as a central endophenotype underlying various psychiatric disorders.}, language = {en} }