@article{ref1,
title="Neural mechanism of a sex-specific risk variant for posttraumatic stress disorder in the Type I receptor of the pituitary adenylate cyclase activating polypeptide",
journal="Biological psychiatry",
year="2015",
author="Pohlack, Sebastian T. and Nees, Frauke and Ruttorf, Michaela and Cacciaglia, Raffaele and Winkelmann, Tobias and Schad, Lothar R. and Witt, Stephanie H. and Rietschel, Marcella and Flor, Herta",
volume="78",
number="12",
pages="840-847",
abstract="BACKGROUND: Posttraumatic stress disorder (PTSD) is a frequent anxiety disorder with higher prevalence rates in female patients than in male patients (2.5:1). Association with a single nucleotide polymorphism (rs2267735) in the gene ADCYAP1R1 encoding the type I receptor (PAC1-R) of the pituitary adenylate cyclase activating polypeptide has been reported with PTSD in female patients. We sought to identify the neural correlates of the described PAC1-R effects on associative learning. <br><br>METHODS: In a reverse genetic approach, we examined two independent healthy samples (N1 = 112, N2 = 73) using functional magnetic resonance imaging during cued and contextual fear conditioning. Skin conductance responses and verbal self-reports of arousal, valence, and contingency were recorded. <br><br>RESULTS: We found that PAC1-R modulates the blood oxygenation level-dependent response of the hippocampus. Specifically, we observed decreased hippocampal activity during contextual, but not during cued, fear conditioning in female participants carrying the PAC1-R risk allele. We observed no significant differences in conditionability for skin conductance responses, verbal reports, or activation in other brain regions between the genotype groups in female participants. <br><br>CONCLUSIONS: Our results suggest that impaired contextual conditioning in the hippocampal formation may mediate the association between PAC1-R and PTSD symptoms. Our findings potentially identify a missing link between the involvement of PAC1-R in PTSD and the well-established structural and functional hippocampal deficits in these patients.<p /> <p>Language: en</p>",
language="en",
issn="0006-3223",
doi="10.1016/j.biopsych.2014.12.018",
url="http://dx.doi.org/10.1016/j.biopsych.2014.12.018"
}