Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development

Croen, Lisa; Qian, Yinge; Ashwood, Paul; Zerbo, Ousseny; Schendel, Diana; Pinto‐Martin, Jennifer; Fallin, M. Daniele; Levy, Susan E.; Schieve, Laura A.; Yeargin‐Allsopp, Marshalyn; Sabourin, Katherine R.; Ames, Jennifer

doi:10.1002/aur.2175

Cited by 74 publications

(70 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another line of evidence comes from studies of environmental exposures associated with ASD. These include studies associating prenatal exposure to valproate [9], as well as to maternal bacterial [10] and viral infections during pregnancy (i.e., cytomegalovirus (CMV)) [11]. These diverse lines of evidence implicate early cortical development as one major convergent period of risk in the development of ASD.…”

mentioning

confidence: 99%

Human in vitro models for understanding mechanisms of autism spectrum disorder

Gordon

Geschwind

2020

Molecular Autism

View full text Add to dashboard Cite

Early brain development is a critical epoch for the development of autism spectrum disorder (ASD). In vivo animal models have, until recently, been the principal tool used to study early brain development and the changes occurring in neurodevelopmental disorders such as ASD. In vitro models of brain development represent a significant advance in the field. Here, we review the main methods available to study human brain development in vitro and the applications of these models for studying ASD and other psychiatric disorders. We discuss the main findings from stem cell models to date focusing on cell cycle and proliferation, cell death, cell differentiation and maturation, and neuronal signaling and synaptic stimuli. To be able to generalize the results from these studies, we propose a framework of experimental design and power considerations for using in vitro models to study ASD. These include both technical issues such as reproducibility and power analysis and conceptual issues such as the brain region and cell types being modeled.Early development as a critical period for ASD susceptibility

show abstract

mentioning

confidence: 99%

Human in vitro models for understanding mechanisms of autism spectrum disorder

Gordon

Geschwind

2020

Molecular Autism

View full text Add to dashboard Cite

show abstract

“…In the past, it was shown that toll-like receptor 3 (TLR3) signaling triggered by poly(IC) was important to induce IL6 and IL17, which in turn played key roles in placental and brain in ammatory signaling that preceded the onset of ASD-like behaviors [74]. In humans, signi cant immunologic challenge and/or in ammation leading to fever during pregnancy, similar to that produced by poly(IC) in mice, is also known to increase the risk of autism [75,76] and schizophrenia [77].…”

Section: Discussionmentioning

confidence: 99%

Metabolic and Behavioral Features of Acute Hyperpurinergia and the Connection to Autism Spectrum Disorder

Zolkipli‐Cunningham

Naviaux

Nakayama

et al. 2020

Preprint

View full text Add to dashboard Cite

Background. Since 2012, studies in mice, rats, and humans have suggested that abnormalities in purinergic signaling may be a final common pathway for many genetic and environmental causes of autism spectrum disorder (ASD). The current study in mice was conducted to characterize the bioenergetic, metabolomic, breathomic, and behavioral features of acute hyperpurinergia triggered by systemic injection of the purinergic agonist and danger signal, extracellular ATP (eATP). Methods. Responses were studied in C57BL/6J mice with ASD-like behaviors in the maternal immune activation (MIA) model and controls. Basal metabolic rates, respiratory exchange ratios (RER = VCO2/VO2), and locomotor activity were measured in CLAMS cages. Plasma metabolomics measured 401 metabolites. Breathomics measured 98 volatile organic compounds. Results. A 0.5 µmol/g dose of ATP dropped whole body oxygen consumption by 74% ± 6% (mean ± SEM, 5,303 to 1,382 ml/kg/hr, p<0.0001) and rectal temperature by 6.2˚ ± 0.3˚C (p<0.0001) in 30 minutes. Over 200 metabolites from 37 different biochemical pathways where changed. MIA animals were hypersensitive to the metabolic and behavioral responses triggered by eATP and poly(IC). Breathomic and metabolomic analysis revealed changes in folate-methylation-1-carbon, purines, pyrimidines, acyl-carnitines, glycolysis, aromatic and branch-chain amino acids, Krebs cycle, glutathione, urea cycle, phospholipids, sphingolipids, eicosanoids, cholesterol, bile acids, vitamins, and microbiome metabolism similar to children with ASD. Limitations. The responses to ATP were studied in only a single genetic strain of mice (C57BL/6J). Although similar to metabolic results reported in FVB mice and a small clinical trial in children with ASD, the generalizability of these results to larger studies in humans is unknown. The chronic effects of repeated postnatal ATP exposures were not tested. Conclusions. Acute hyperpurinergia produced metabolic and behavioral changes in mice that were similar to those found in children with ASD. These behaviors and metabolic changes were associated with mitochondrial functional changes that were profound but reversible.

show abstract

“…Firstly, the lack of association observed between prenatal infections and pervasive development disorders, which was replaced by ASD in the DSM-V (American Psychiatric Association, 2013), should be noted, as it contradicts a large body of evidence suggesting the contrary (Jiang et al, 2016). Complementary evidence (Croen et al, 2019) has, however, suggested that it may not be the infectious agents themselves which are associated with abnormal neurodevelopment, but rather the accompanying immune activation, relating to side attributes such as fever. This aligns with findings from studies reporting links between prenatal levels of biomarkers such as inflammatory cytokines and increased odds of ASD in offspring (Goines et al, 2011;Abdallah et al, 2013;Zerbo et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Prenatal maternal infections and psychopathology in childhood and adolescence: Findings from the ALSPAC birth cohort

Hall¹,

Speyer²,

Lombardo³

et al. 2020

Preprint

View full text Add to dashboard Cite

Aims: Studies have suggested that exposure to prenatal infections may be a risk factor in the aetiology of neurodevelopmental disorders such as schizophrenia and autism, but that its effects may differ by timing of exposure. Evidence on other psychiatric outcomes, however, is scarce and mixed. The aims of this study were to examine whether exposure to infections, at any point in gestation and during each trimester, is associated with increased odds of psychiatric disorders (pervasive developmental disorders, attention-deficit hyperactivity disorder, behavioural disorders and emotional disorders) at ages 7 and 14. Methods: Participants were n = 8859 mother and child pairs from the UK Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Exposure to prenatal infections was assessed for each trimester using maternal self-reports. Children’s psychiatric status was assessed using the parent-reported Development and Well-being Assessment (DAWBA). Logistic regressions were used to examine links between prenatal infections and child outcomes. Results: Half of the mothers reported an infection at some point during pregnancy and 7% of children were reported to have a psychiatric condition. Increased odds of children having any psychiatric disorder at age 14 were found in association with infections at any point during pregnancy, OR = 1.27 (95% CI 1.04, 1.55) and in the third trimester specifically, OR = 1.28 (95% CI 1.02, 1.61), after adjusting for the effects of potential confounds and other covariates. No other links were found in adjusted models. Conclusions: Findings suggest that associations between prenatal infections and children’s psychiatric disorders are weak to non-existent, after adjusting for the effects of other factors.

show abstract

Infection and Fever in Pregnancy and Autism Spectrum Disorders: Findings from the Study to Explore Early Development

Cited by 74 publications

References 40 publications

Human in vitro models for understanding mechanisms of autism spectrum disorder

Human in vitro models for understanding mechanisms of autism spectrum disorder

Metabolic and Behavioral Features of Acute Hyperpurinergia and the Connection to Autism Spectrum Disorder

Prenatal maternal infections and psychopathology in childhood and adolescence: Findings from the ALSPAC birth cohort

Contact Info

Product

Resources

About