PAC1R Genotype to Phenotype Correlations in Autism Spectrum Disorder.
A PTSD-linked gene makes social deficits and amygdala wiring worse in kids who already have autism.
01Research in Context
What this study did
Goodrich et al. (2019) looked at one gene, PAC1R, in people who already have autism.
They asked: does the PTSD-risk version of this gene change how bad social problems are?
Parents filled out a survey about social skills while kids had a short brain scan.
What they found
Kids with the CC form of PAC1R had worse parent-rated social deficits.
The same kids also showed stronger amygdala-to-MTG brain links while resting.
In short, a PTSD-risk gene makes social brain wiring and behavior more severe in ASD.
How this fits with other research
Chen et al. (2021) extends this idea. They saw that autistic youths with anxiety also have extra amygdala wiring, but only when viewing threat faces.
Koegel et al. (2014) seems to flip the story: mothers with PTSD symptoms were two-to-three times more likely to have a child with ASD. The two papers do not clash. Meredith studied kids who already have ASD and asked why symptoms differ. L studied the general population and asked who gets the diagnosis. Different questions, both useful.
Gilmore et al. (2022) adds a family angle: when parents carry PTSD, their autistic kids enter hospitals with more abuse histories. The gene finding plus family stress data hint at a loop where risk travels from parent to child and back.
Why it matters
You cannot change genes, but you can flag risk early. If an autistic client carries the PAC1R CC form, expect steeper social goals and consider adding anxiety screens. Pair this with parent PTSD checks from Koegel et al. (2014) and trauma questions from Gilmore et al. (2022). A quick parent survey plus a glance at the referral genetics note can sharpen your assessment and justify added social or trauma-focused supports.
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02At a glance
03Original abstract
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.
Autism research : official journal of the International Society for Autism Research, 2019 · doi:10.1093/nar/gkq537