The pituitary adenylate cyclase-activating polypeptide system as a sex-specific modulator of hippocampal response to threat stimuli

Daniel Porta-Casteràs; Marta Cano; Trevor Steward; Raül Andero; Narcís Cardoner

doi:10.1016/j.ynstr.2022.100448

The pituitary adenylate cyclase-activating polypeptide system as a sex-specific modulator of hippocampal response to threat stimuli

Daniel Porta-Casteràs, Marta Cano^*, Trevor Steward, Raül Andero, Narcís Cardoner

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

1 Citation (Scopus)

Abstract

Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor gene polymorphism has been postulated as a potential sex-specific diagnostic biomarker of trauma-related disorders. However, no research to date has evaluated whether the PACAPergic system may act as a vulnerability/resilience neuromechanism to trauma-induced psychopathology in healthy participants without heightened risk to experience traumatic events. Methods: Here, we compared the amygdala and hippocampus response to fearful faces in participants with at-risk genotype versus non-risk participants from the Human Connectome Project (n = 991; 53.4% female). Results: Increased hippocampal response to fearful faces in the female risk group emerged in sex by genetic risk interaction. Conclusions: Our findings revealed the first sex-specific neurogenetic vulnerability factor to trauma-related disorders, and emphasize the importance of prevention-based strategies to ameliorate neuropsychiatric pathophysiology.

Original language	English
Article number	100448
Pages (from-to)	1-7
Number of pages	7
Journal	Neurobiology of Stress
Volume	18
DOIs	https://doi.org/10.1016/j.ynstr.2022.100448
Publication status	Published - 1 May 2022

Keywords

fMRI
Hippocampus
PACAP
PTSD
Threat
Women

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ynstr.2022.100448Licence: CC BY-NC-ND

Cite this

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title = "The pituitary adenylate cyclase-activating polypeptide system as a sex-specific modulator of hippocampal response to threat stimuli",

abstract = "Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor gene polymorphism has been postulated as a potential sex-specific diagnostic biomarker of trauma-related disorders. However, no research to date has evaluated whether the PACAPergic system may act as a vulnerability/resilience neuromechanism to trauma-induced psychopathology in healthy participants without heightened risk to experience traumatic events. Methods: Here, we compared the amygdala and hippocampus response to fearful faces in participants with at-risk genotype versus non-risk participants from the Human Connectome Project (n = 991; 53.4% female). Results: Increased hippocampal response to fearful faces in the female risk group emerged in sex by genetic risk interaction. Conclusions: Our findings revealed the first sex-specific neurogenetic vulnerability factor to trauma-related disorders, and emphasize the importance of prevention-based strategies to ameliorate neuropsychiatric pathophysiology.",

keywords = "fMRI, Hippocampus, PACAP, PTSD, Threat, Women",

author = "Daniel Porta-Caster{\`a}s and Marta Cano and Trevor Steward and Ra{\"u}l Andero and Narc{\'i}s Cardoner",

note = "Funding information: Instituto de Salud Carlos III PFIS grant FI19/00251 (DPC). Instituto de Salud Carlos III Sara Borrell grant CD20/00189 (MC). National Health and Medical Research Council/Medical Research Future Fund Investigator grant MRF1193736 (TS). Brain & Behavior Research Foundation Young Investigator Grant (TS). Brain & Behavior Research Foundation Young Investigator Grant #22434 (RA). University of Melbourne McKenzie Fellowship (TS). Ministerio de Econom{\'i}a y Competitividad, Ram{\'o}n y Cajal program RYC2014-15784 (RA). Ministerio de Econom{\'i}a y Competitividad, RETOS-MICINN SAF2016-76565-R (RA). Ministerio de Econom{\'i}a y Competitividad, RETOS-MICINN, PID2020-112705RB-I00 (RA). Fundaci{\'o}n Alicia Koplowitz (RA). Network of European Funding for Neuroscience Research through the European Commission, ERA-NET Neuron JTC 2019 ISCIII AC19/00077 (RA). Network of European Funding for Neuroscience Research through the European Commission, ERA-NET Neuron JTC 2019 ISCIII AC19/00088 (NC). Publisher Copyright: {\textcopyright} 2022 The Authors",

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doi = "10.1016/j.ynstr.2022.100448",

language = "English",

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T1 - The pituitary adenylate cyclase-activating polypeptide system as a sex-specific modulator of hippocampal response to threat stimuli

AU - Porta-Casteràs, Daniel

AU - Cano, Marta

AU - Steward, Trevor

AU - Andero, Raül

AU - Cardoner, Narcís

N1 - Funding information: Instituto de Salud Carlos III PFIS grant FI19/00251 (DPC). Instituto de Salud Carlos III Sara Borrell grant CD20/00189 (MC). National Health and Medical Research Council/Medical Research Future Fund Investigator grant MRF1193736 (TS). Brain & Behavior Research Foundation Young Investigator Grant (TS). Brain & Behavior Research Foundation Young Investigator Grant #22434 (RA). University of Melbourne McKenzie Fellowship (TS). Ministerio de Economía y Competitividad, Ramón y Cajal program RYC2014-15784 (RA). Ministerio de Economía y Competitividad, RETOS-MICINN SAF2016-76565-R (RA). Ministerio de Economía y Competitividad, RETOS-MICINN, PID2020-112705RB-I00 (RA). Fundación Alicia Koplowitz (RA). Network of European Funding for Neuroscience Research through the European Commission, ERA-NET Neuron JTC 2019 ISCIII AC19/00077 (RA). Network of European Funding for Neuroscience Research through the European Commission, ERA-NET Neuron JTC 2019 ISCIII AC19/00088 (NC). Publisher Copyright: © 2022 The Authors

PY - 2022/5/1

Y1 - 2022/5/1

N2 - Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor gene polymorphism has been postulated as a potential sex-specific diagnostic biomarker of trauma-related disorders. However, no research to date has evaluated whether the PACAPergic system may act as a vulnerability/resilience neuromechanism to trauma-induced psychopathology in healthy participants without heightened risk to experience traumatic events. Methods: Here, we compared the amygdala and hippocampus response to fearful faces in participants with at-risk genotype versus non-risk participants from the Human Connectome Project (n = 991; 53.4% female). Results: Increased hippocampal response to fearful faces in the female risk group emerged in sex by genetic risk interaction. Conclusions: Our findings revealed the first sex-specific neurogenetic vulnerability factor to trauma-related disorders, and emphasize the importance of prevention-based strategies to ameliorate neuropsychiatric pathophysiology.

AB - Background: Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor gene polymorphism has been postulated as a potential sex-specific diagnostic biomarker of trauma-related disorders. However, no research to date has evaluated whether the PACAPergic system may act as a vulnerability/resilience neuromechanism to trauma-induced psychopathology in healthy participants without heightened risk to experience traumatic events. Methods: Here, we compared the amygdala and hippocampus response to fearful faces in participants with at-risk genotype versus non-risk participants from the Human Connectome Project (n = 991; 53.4% female). Results: Increased hippocampal response to fearful faces in the female risk group emerged in sex by genetic risk interaction. Conclusions: Our findings revealed the first sex-specific neurogenetic vulnerability factor to trauma-related disorders, and emphasize the importance of prevention-based strategies to ameliorate neuropsychiatric pathophysiology.

KW - fMRI

KW - Hippocampus

KW - PACAP

KW - PTSD

KW - Threat

KW - Women

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DO - 10.1016/j.ynstr.2022.100448

M3 - Article

C2 - 35685680

AN - SCOPUS:85129568525

SN - 2352-2895

VL - 18

SP - 1

EP - 7

JO - Neurobiology of Stress

JF - Neurobiology of Stress

M1 - 100448

ER -

The pituitary adenylate cyclase-activating polypeptide system as a sex-specific modulator of hippocampal response to threat stimuli

Abstract

Keywords

UN SDGs

Access to Document

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DIFERENCIAS DE SEXO EN LA MEMORIA DE MIEDO

BioStress: Translational biomarkers of traumatic stress

Microcircuitos y macrocircuitos de la via tac2 en aprendizaje del miedo

Cite this

The pituitary adenylate cyclase-activating polypeptide system as a sex-specific modulator of hippocampal response to threat stimuli

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

DIFERENCIAS DE SEXO EN LA MEMORIA DE MIEDO

BioStress: Translational biomarkers of traumatic stress

Microcircuitos y macrocircuitos de la via tac2 en aprendizaje del miedo

Cite this