Lymphocytic Extracellular Signal-Regulated Kinase Dysregulation in Autism Spectrum Disorder.

Autor: Erickson CA; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: craig.erickson@cchmc.org., Tessier CR; Indiana University School of Medicine, South Bend, Indiana., Gross C; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Pedapati EV; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Wink LK; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Dominick KC; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Shaffer RC; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Rosselot H; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Hong MP; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Bantel AP; Indiana University School of Medicine, South Bend, Indiana., Berry-Kravis E; Rush University School of Medicine, Chicago, Illinois., Horn PS; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Adams R; Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio., Sweeney JA; University of Cincinnati College of Medicine, Cincinnati, Ohio.
Jazyk: angličtina
Zdroj: Journal of the American Academy of Child and Adolescent Psychiatry [J Am Acad Child Adolesc Psychiatry] 2023 May; Vol. 62 (5), pp. 582-592.e2. Date of Electronic Publication: 2023 Jan 10.
DOI: 10.1016/j.jaac.2022.09.437
Abstrakt: Objective: Extracellular signal-regulated kinase (ERK1/2) is a conserved central intracellular signaling cascade involved in many aspects of neuronal development and plasticity. Converging evidence support investigation of ERK1/2 activity in autism spectrum disorder (ASD). We previously reported enhanced baseline lymphocytic ERK1/2 activation in autism, and now we extend our work to investigate the early phase kinetics of lymphocytic ERK1/2 activation in idiopathic ASD.
Method: Study participants included 67 individuals with ASD (3-25 years of age), 65 age- and sex-matched typical developing control (TDC) subjects, and 36 age-, sex-, and IQ-matched developmental disability control (DDC) subjects matched to those with ASD and IQ <90. We completed an additional analysis comparing results from ASD, TDC, and DDC groups with data from 37 individuals with Fragile X syndrome (FXS). All subjects had blood lymphocyte samples analyzed by flow cytometry following stimulation with phorbol ester and sequentially analyzed for ERK1/2 activation (phosphorylation) at several time points.
Results: The ASD group (mean = 5.81 minutes; SD = 1.5) had a significantly lower (more rapid) mean ERK1/2 T 1/2 activation value than both the DDC group (mean = 6.78 minutes; SD = 1.6; p = .00078) and the TDC group (mean = 6.4 minutes; SD = 1.5; p = .025). More rapid ERK1/2 T 1/2 activation times did correlate with increased social impairment across all study groups including the ASD cohort. Differences in ERK1/2 T 1/2 activation were more pronounced in younger than in older individuals in the primary analysis. The ASD group additionally had more rapid activation times than the FXS group, and the FXS group activation kinetics did not differ from those of the TDC and DDC groups.
Conclusion: Our findings indicate that lymphocytic ERK1/2 activation kinetics are dysregulated in persons with ASD, marked by more rapid early phase activation. Group differences in ERK1/2 activation kinetics appear to be driven by findings from the youngest children analyzed.
Diversity & Inclusion Statement: We worked to ensure sex and gender balance in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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