PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder.
Adolescent
Animals
Autism Spectrum Disorder
/ genetics
Brain
/ diagnostic imaging
Brain Mapping
/ methods
Child
Disease Models, Animal
Female
Genotype
Humans
Magnetic Resonance Imaging
/ methods
Male
Mice
Mice, Inbred C57BL
Phenotype
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
/ genetics
PAC1R
amygdala
autism
genetic modifier
neuroimaging
Journal
Autism research : official journal of the International Society for Autism Research
ISSN: 1939-3806
Titre abrégé: Autism Res
Pays: United States
ID NLM: 101461858
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
03
05
2018
revised:
10
09
2018
accepted:
21
10
2018
pubmed:
18
12
2018
medline:
25
2
2020
entrez:
18
12
2018
Statut:
ppublish
Résumé
Amygdala dysfunction has been implicated in numerous neurodevelopmental disorders, including autism spectrum disorder (ASD). Previous studies in mice and humans, respectively, have linked Pac1r/PAC1R function to social behavior and PTSD-susceptibility. Based on this connection to social and emotional processing and the central role played by the amygdala in ASD, we examined a putative role for PAC1R in social deficits in ASD and determined the pattern of gene expression in the developing mouse and human amygdala. We reveal that Pac1r/PAC1R is expressed in both mouse and human amygdala from mid-neurogenesis through early postnatal stages, critical time points when altered brain trajectories are hypothesized to unfold in ASD. We further find that parents of autistic children carrying a previously identified PTSD-risk genotype (CC) report greater reciprocal social deficits compared to those carrying the non-risk GC genotype. Additionally, by exploring resting-state functional connectivity differences in a subsample of the larger behavioral sample, we find higher functional connectivity between the amygdala and right middle temporal gyrus in individuals with the CC risk genotype. Thus, using multimodal approaches, our data reveal that the amygdala-expressed PAC1R gene may be linked to severity of ASD social phenotype and possible alterations in brain connectivity, therefore potentially acting as a modifier of amygdala-related phenotypes. Autism Res 2019, 12: 200-211 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this multimodal study across mouse and human, we examined expression patterns of Pac1r/PAC1R, a gene implicated in social behavior, and further explored whether a previously identified human PTSD-linked mutation in PAC1R can predict brain connectivity and social deficits in ASD. We find that PAC1R is highly expressed in the both the mouse and human amygdala. Furthermore, our human data suggest that PAC1R genotype is linked to severity of social deficits and functional amygdala connectivity in ASD.
Identifiants
pubmed: 30556326
doi: 10.1002/aur.2051
pmc: PMC6665682
mid: NIHMS1040346
doi:
Substances chimiques
ADCYAP1R1 protein, human
0
Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
200-211Subventions
Organisme : NIDA NIH HHS
ID : R01 DA020140
Pays : United States
Organisme : NICHD NIH HHS
ID : U54 HD090257
Pays : United States
Informations de copyright
© 2018 International Society for Autism Research, Wiley Periodicals, Inc.
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