Version 1
: Received: 4 June 2024 / Approved: 4 June 2024 / Online: 4 June 2024 (16:10:31 CEST)
How to cite:
Jones, J. P.; Williamson, L.; Konsoula, Z.; Anderson, R.; Reissner, K. J.; Parker, W. Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism. Preprints2024, 2024060154. https://doi.org/10.20944/preprints202406.0154.v1
Jones, J. P.; Williamson, L.; Konsoula, Z.; Anderson, R.; Reissner, K. J.; Parker, W. Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism. Preprints 2024, 2024060154. https://doi.org/10.20944/preprints202406.0154.v1
Jones, J. P.; Williamson, L.; Konsoula, Z.; Anderson, R.; Reissner, K. J.; Parker, W. Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism. Preprints2024, 2024060154. https://doi.org/10.20944/preprints202406.0154.v1
APA Style
Jones, J. P., Williamson, L., Konsoula, Z., Anderson, R., Reissner, K. J., & Parker, W. (2024). Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism. Preprints. https://doi.org/10.20944/preprints202406.0154.v1
Chicago/Turabian Style
Jones, J. P., Kathryn J Reissner and William Parker. 2024 "Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism" Preprints. https://doi.org/10.20944/preprints202406.0154.v1
Abstract
More than 20 lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations previously indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in-silico methods to create an ideal (virtual) population of 120000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal data set shows little to no risk of acetaminophen use if cofactors which create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors which impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Commenter's Conflict of Interests:
I am one of the authors.
Comment:
Three numerical errors are present, one in Figure 3 and one in each of the Table Captions.
As described in the methods, the prevalence of ASD in the virtual data set was set at 1/36 (2.78%), and half of that (1.39%) was induced by oxidative stress and acetaminophen exposure. With that in mind, the following changes need to be made:
Table 1 caption: 0.278% should be 1.39%.
Table 2 caption: 0.278% should be 1.39%.
Figure 3: 0.028% should be 2.78%.
Commenter:
Commenter's Conflict of Interests: I am one of the authors.
As described in the methods, the prevalence of ASD in the virtual data set was set at 1/36 (2.78%), and half of that (1.39%) was induced by oxidative stress and acetaminophen exposure. With that in mind, the following changes need to be made:
Table 1 caption: 0.278% should be 1.39%.
Table 2 caption: 0.278% should be 1.39%.
Figure 3: 0.028% should be 2.78%.
We apologize for the errors.