BACKGROUND: Behavioral inhibition to the unfamiliar (BI), a heritable temperamental profile involving an avoidant response to novel situations, may be an intermediate phenotype in the development of anxiety disorders. Corticotropin-releasing hormone (CRH) is a key mediator of the stress response through its effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems. Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype. METHODS: We genotyped a marker tightly linked to the CRH locus in 85 families of children who underwent laboratory-based behavioral assessments of BI and performed family-based association analyses. RESULTS: We observed an association between an allele of the CRH-linked locus and BI (p =.015). Among offspring of parents with panic disorder, this association was particularly marked (p =.0009). We further demonstrate linkage disequilibrium between this marker and single nucleotide polymorphisms encompassing the CRH gene. CONCLUSIONS: These results are consistent with the possibility that variants in the CRH gene are associated with anxiety proneness.
BACKGROUND: Behavioral inhibition to the unfamiliar (BI), a heritable temperamental profile involving an avoidant response to novel situations, may be an intermediate phenotype in the development of anxiety disorders. Corticotropin-releasing hormone (CRH) is a key mediator of the stress response through its effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems. Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype. METHODS: We genotyped a marker tightly linked to the CRH locus in 85 families of children who underwent laboratory-based behavioral assessments of BI and performed family-based association analyses. RESULTS: We observed an association between an allele of the CRH-linked locus and BI (p =.015). Among offspring of parents with panic disorder, this association was particularly marked (p =.0009). We further demonstrate linkage disequilibrium between this marker and single nucleotide polymorphisms encompassing the CRH gene. CONCLUSIONS: These results are consistent with the possibility that variants in the CRH gene are associated with anxiety proneness.
Authors: Frieder M Paulus; Sören Krach; Johannes Bedenbender; Martin Pyka; Jens Sommer; Axel Krug; Susanne Knake; Markus M Nöthen; Stephanie H Witt; Marcella Rietschel; Tilo Kircher; Andreas Jansen Journal: Hum Brain Mapp Date: 2011-10-31 Impact factor: 5.038
Authors: R Parrish Waters; Marion Rivalan; D A Bangasser; J M Deussing; M Ising; S K Wood; F Holsboer; Cliff H Summers Journal: Neurosci Biobehav Rev Date: 2015-08-10 Impact factor: 8.989
Authors: Christina S Barr; Rachel L Dvoskin; Qiaoping Yuan; Robert H Lipsky; Manisha Gupte; Xian Hu; Zhifeng Zhou; Melanie L Schwandt; Stephen G Lindell; Megan McKee; Michelle L Becker; Mitchel A Kling; Phillip W Gold; Dee Higley; Markus Heilig; Stephen J Suomi; David Goldman Journal: Arch Gen Psychiatry Date: 2008-08