@article{WeberScholzDomschkeetal.2012,
  author    = {Weber, Heike and Scholz, Claus J{\"u}rgen and Domschke, Katharina and Baumann, Christian and Klauke, Benedikt and Jacob, Christian P. and Maier, Wolfgang and Fritze, J{\"u}rgen and Bandelow, Borwin and Zwanzger, Peter Michael and Lang, Thomas and Fehm, Lydia and Str{\"o}hle, Andreas and Hamm, Alfons and Gerlach, Alexander L. and Alpers, Georg W. and Kircher, Tilo and Wittchen, Hans-Ulrich and Arolt, Volker and Pauli, Paul and Deckert, J{\"u}rgen and Reif, Andreas},
  title     = {Gender Differences in Associations of Glutamate Decarboxylase 1 Gene (GAD1) Variants with Panic Disorder},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75830},
  year      = {2012},
  abstract  = {Background: Panic disorder is common (5\% prevalence) and females are twice as likely to be affected as males. The heritable component of panic disorder is estimated at 48\%. Glutamic acid dehydrogenase GAD1, the key enzyme for the synthesis of the inhibitory and anxiolytic neurotransmitter GABA, is supposed to influence various mental disorders, including mood and anxiety disorders. In a recent association study in depression, which is highly comorbid with panic disorder, GAD1 risk allele associations were restricted to females. Methodology/Principal Findings: Nineteen single nucleotide polymorphisms (SNPs) tagging the common variation in GAD1 were genotyped in two independent gender and age matched case-control samples (discovery sample n = 478; replication sample n = 584). Thirteen SNPs passed quality control and were examined for gender-specific enrichment of risk alleles associated with panic disorder by using logistic regression including a genotype6gender interaction term. The latter was found to be nominally significant for four SNPs (rs1978340, rs3762555, rs3749034, rs2241165) in the discovery sample; of note, the respective minor/risk alleles were associated with panic disorder only in females. These findings were not confirmed in the replication sample; however, the genotype6gender interaction of rs3749034 remained significant in the combined sample. Furthermore, this polymorphism showed a nominally significant association with the Agoraphobic Cognitions Questionnaire sum score. Conclusions/Significance: The present study represents the first systematic evaluation of gender-specific enrichment of risk alleles of the common SNP variation in the panic disorder candidate gene GAD1. Our tentative results provide a possible explanation for the higher susceptibility of females to panic disorder.},
  subject      = {Medizin},
  language  = {en}
}
@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}
}