TY  - JOUR
PY  - 2015//
TI  - Neural mechanism of a sex-specific risk variant for posttraumatic stress disorder in the Type I receptor of the pituitary adenylate cyclase activating polypeptide
JO  - Biological psychiatry
A1  - Pohlack, Sebastian T.
A1  - Nees, Frauke
A1  - Ruttorf, Michaela
A1  - Cacciaglia, Raffaele
A1  - Winkelmann, Tobias
A1  - Schad, Lothar R.
A1  - Witt, Stephanie H.
A1  - Rietschel, Marcella
A1  - Flor, Herta
SP  - 840
EP  - 847
VL  - 78
IS  - 12
N2  - 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>
LA  - en
SN  - 0006-3223
UR  - http://dx.doi.org/10.1016/j.biopsych.2014.12.018
ID  - ref1
ER  -