Neural Mechanism of a Sex-Specific Risk Variant for Posttraumatic Stress Disorder in the Type I Receptor of the Pituitary Adenylate Cyclase Activating Polypeptide

作者：Pohlack Sebastian T; Nees Frauke; Ruttorf Michaela; Cacciaglia Raffaele; Winkelmann Tobias; Schad Lothar R; Witt Stephanie H; Rietschel Marcella; Flor Herta^*

来源：Biological Psychiatry, 2015, 78(12): 840-847.

DOI：10.1016/j.biopsych.2014.12.018

• ADCYAP1R1
• Amygdala
• Fear conditioning
• Functional magnetic resonance imaging
• Hippocampus
• PTSD

BACKGROUND: Posttraumatic stress disorder (PTSD) is a frequent anxiety disorder with higher prevalence rates infemale 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 (N-1 = 112, N-2 = 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.

• 出版日期2015-12-15
• 单位上海市精神卫生中心