Distinct Patterns of GABAergic Interneuron Pathology in Autism Are Associated with Intellectual Impairment and Stereotypic Behaviors

Autor/inn/en	Dufour, Brett D.; McBride, Erin; Bartley, Trevor; Juarez, Pablo; Martínez-Cerdeño, Verónica
Titel	Distinct Patterns of GABAergic Interneuron Pathology in Autism Are Associated with Intellectual Impairment and Stereotypic Behaviors
Quelle	In: Autism: The International Journal of Research and Practice, 27 (2023) 6, S.1730-1745 (16 Seiten) PDF als Volltext Verfügbarkeit
Zusatzinformation	ORCID (Martínez-Cerdeño, Verónica)
Sprache	englisch
Dokumenttyp	gedruckt; online; Zeitschriftenaufsatz
ISSN	1362-3613
DOI	10.1177/13623613231154053
Schlagwörter	Autism Spectrum Disorders; Symptoms (Individual Disorders); Behavior Problems; Intellectual Disability; Brain Hemisphere Functions; Correlation; Severity (of Disability); Comorbidity; Pathology + Suchen Sie Ihr Suchwort? Autism; Autismus; Psychiatrische Symptomatik; Intellect; Disability; Disabilities; Verstand; Behinderung; Korrelation; Schweregrad; Pathologie
Abstract	Autism spectrum disorder is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviors. How specific anatomical alterations contribute to the clinical profile of autism spectrum disorder remains largely uncharacterized. We have previously shown that parvalbumin-positive Chandelier cells, a specific type of GABAergic interneuron, are reduced in number in the autism spectrum disorder prefrontal cortex. Here, we assessed the relationship between interneuron pathology with autism spectrum disorder symptom severity and comorbidity. We collected clinical records from autism (n = 20) and control (n = 19) brain donors, from whom we previously characterized GABAergic interneuron pathology in three regions of the prefrontal cortex (BA9, 46, and 47). We assessed the relationship between the severity of core symptoms, as indicated by Autism Diagnostic Interview--Revised scores, and Chandelier cell pathology in autism spectrum disorder, and also differences in interneuron pathology associated with autism spectrum disorder comorbidities. Total GABAergic interneuron number was significantly reduced in autism spectrum disorder cases with intellectual disability in the prefrontal cortex (PFC )--by 36.6% relative to autism spectrum disorder without intellectual disability and by 38.7% relative to neurotypical controls. The severity of autism spectrum disorder motor stereotypies was correlated with the severity of Chandelier cell loss in BA47, as indicated by reductions in parvalbumin[superscript +] interneurons and GABA transporter 1[superscript +] cartridges. Chandelier cell loss is associated with the core autism spectrum disorder symptom domain of restricted repetitive behaviors and likely plays a role in stereotypic motor mannerisms. Intellectual impairment in autism spectrum disorder reflects a more severe form of a common underlying neuropathology-cortical GABAergic interneuron loss. (As Provided).
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Erfasst von	ERIC (Education Resources Information Center), Washington, DC
Update	2024/1/01