Citation

Pohlack ST, Nees F, Ruttorf M, Cacciaglia R, Winkelmann T, Schad LR, Witt SH, Rietschel M, Flor H. Biol. Psychiatry 2015; 78(12): 840-847.

Affiliation

Departments of Cognitive and Clinical Neuroscience, Medical Faculty Mannheim, Heidelberg University, Germany. Electronic address: herta.flor@zi-mannheim.de.

Copyright

(Copyright © 2015, Elsevier Publishing)

DOI

10.1016/j.biopsych.2014.12.018

PMID

25680674

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.

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.

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.

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.

Language: en