Brain function distinguishes female carriers and non-carriers of familial risk for autism

Molecular Autism

Ally Dworetsky¹  Alana McMichael¹  Steven E. Petersen¹  Rebecca Coalson¹  Babatunde Adeyemo¹  Savannah Davis²  John R. Pruett²  John N. Constantino²  Daniel Gray²  Zoë Hawks³  Adam T. Eggebrecht⁴ 

[1] Department of Neurology, Washington University School of Medicine, 660 S. Euclid Ave, 63110, St Louis, MO, USA;Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave, 63110, St Louis, MO, USA;Department of Psychological and Brain Sciences, Washington University in St. Louis, 1 Brookings Dr., 63130, St Louis, MO, USA;Mallinckrodt Institute of Radiology, Washington University School of Medicine, 660 S. Euclid Ave, 63110, St Louis, MO, USA;Washington University School of Medicine, C.B. 8225, 4515 McKinley Ave., 63110, St. Louis, MO, USA;

关键词: Sex ratio;    Endophenotype;    Biological motion;    Silent transmission;    Familial risk;   

DOI  :  10.1186/s13229-020-00381-y

来源: Springer

【 摘 要 】

BackgroundAutism spectrum disorder (ASD) is characterized by high population-level heritability and a three-to-one male-to-female ratio that occurs independent of sex linkage. Prior research in a mixed-sex pediatric sample identified neural signatures of familial risk elicited by passive viewing of point light motion displays, suggesting the possibility that both resilience and risk of autism might be associated with brain responses to biological motion. To confirm a relationship between these signatures and inherited risk of autism, we tested them in families enriched for genetic loading through undiagnosed (“carrier”) females.MethodsUsing functional magnetic resonance imaging, we examined brain responses to passive viewing of point light displays—depicting biological versus non-biological motion—in a sample of undiagnosed adult females enriched for inherited susceptibility to ASD on the basis of affectation in their respective family pedigrees. Brain responses in carrier females were compared to responses in age-, SRS-, and IQ-matched non-carrier-females—i.e., females unrelated to individuals with ASD. We conducted a hypothesis-driven analysis focused on previously published regions of interest as well as exploratory, brain-wide analyses designed to characterize more fully the rich responses to this paradigm.ResultsWe observed robust responses to biological motion. Notwithstanding, the 12 regions implicated by prior research did not exhibit the hypothesized interaction between group (carriers vs. controls) and point light displays (biological vs. non-biological motion). Exploratory, brain-wide analyses identified this interaction in three novel regions. Post hoc analyses additionally revealed significant variations in the time course of brain activation in 20 regions spanning occipital and temporal cortex, indicating group differences in response to point light displays (irrespective of the nature of motion) for exploration in future studies.LimitationsWe were unable to successfully eye-track all participants, which prevented us from being able to control for potential differences in eye gaze position.ConclusionsThese methods confirmed pronounced neural signatures that differentiate brain responses to biological and scrambled motion. Our sample of undiagnosed females enriched for family genetic loading enabled discovery of numerous contrasts between carriers and non-carriers of risk of ASD that may index variations in visual attention and motion processing related to genetic susceptibility and inform our understanding of mechanisms incurred by inherited liability for ASD.

【 授权许可】

CC BY