Maternal cytomegalovirus sero‐positivity and autism symptoms in children

Slawinski, Brooke L.; Talge, Nicole M.; Ingersoll, Brooke; Smith, Arianna; Glazier, Alicynne; Kerver, Jean M.; Paneth, Nigel; Racicot, Karen

doi:10.1111/aji.12840

Cited by 42 publications

(30 citation statements)

References 46 publications

(49 reference statements)

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“…Several lines of evidence suggest a role of inflammation in the underlying developmental mechanisms of ASD (4–6). Epidemiological studies show an association between maternal infection [such as influenza (7) or cytomegalovirus (8)] during pregnancy and increased risk of offspring autism (9, 10). Also, family history of autoimmune diseases is associated with higher rate of ASD (11).…”

Section: Introductionmentioning

confidence: 99%

Review of Clinical Studies Targeting Inflammatory Pathways for Individuals With Autism

2019

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Immune dysfunction and abnormal immune response may be associated with certain mechanisms underlying autism spectrum disorder (ASD). The early evidence for this link was based on the increased incidence of ASD in children with a history of maternal infection during pregnancy. Observational studies show increased prevalence of immune-related disorders—ranging from atopy, food allergy, viral infections, asthma, primary immunodeficiency, to autoimmune disorders—in individuals with ASD and their families. Evidence of neuroglial activation and focal brain inflammation in individuals with ASD implies that the central nervous system immunity may also be atypical in some individuals with ASD. Also, both peripheral and central inflammatory responses are suggested to be associated with ASD-related behavioral symptoms. Atypical immune responses may be evident in specific ASD subgroups, such as those with significant gastrointestinal symptoms. The present review aimed to evaluate current literature of potential interventions that target inflammatory pathways for individuals with ASD and to summarize whether these interventions were associated with improvement in autism symptoms and adaptation. We found that the current literature on the efficacy of anti-inflammatory interventions in ASD is still limited and large-scale randomized controlled trials are needed to provide robust evidence. We concluded that the role of immune-mediated mechanisms in the emergence of ASD or related challenges may be specific to subsets of individuals (e.g. those with concurrent immunological disorders, developmental regression, or high irritability). These subsets of individuals of ASD might be more likely to benefit from interventions that target immune-mediated mechanisms and with whom next-stage immune-mediated clinical trials could be conducted.

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Section: Introductionmentioning

confidence: 99%

Review of Clinical Studies Targeting Inflammatory Pathways for Individuals With Autism

2019

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“…Our database also includes various types of environmentally induced models for autism reported in the scientific literature. Several prenatal factors, including exposure to drugs [ 13 ], role of paternal age [ 14 ], and maternal immune factors circulating during gestation [ 15 ], are being studied as causative or modulatory inducers of ASD. Additionally, the complex effects of chemical exposure and drugs after birth are also undergoing scrutiny [ 16 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

A multifaceted approach for analyzing complex phenotypic data in rodent models of autism

et al. 2019

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Autism (MIM 209850) is a multifactorial disorder with a broad clinical presentation. A number of high-confidence ASD risk genes are known; however, the contribution of non-genetic environmental factors towards ASD remains largely uncertain. Here, we present a bioinformatics resource of genetic and induced models of ASD developed using a shared annotation platform. Using this data, we depict the intricate trends in the research approaches to analyze rodent models of ASD. We identify the top 30 most frequently studied phenotypes extracted from rodent models of ASD based on 787 publications. As expected, many of these include animal model equivalents of the “core” phenotypes associated with ASD, such as impairments in social behavior and repetitive behavior, as well as several comorbid features of ASD including anxiety, seizures, and motor-control deficits. These phenotypes have also been studied in models based on a broad range of environmental inducers present in the database, of which gestational exposure to valproic acid (VPA) and maternal immune activation models comprising lipopolysaccharide (LPS) and poly I:C are the most studied. In our unique dataset of rescue models, we identify 24 pharmaceutical agents tested on established models derived from various ASD genes and CNV loci for their efficacy in mitigating symptoms relevant for ASD. As a case study, we analyze a large collection of Shank3 mouse models providing a high-resolution view of the in vivo role of this high-confidence ASD gene, which is the gateway towards understanding and dissecting the heterogeneous phenotypes seen in single-gene models of ASD. The trends described in this study could be useful for researchers to compare ASD models and to establish a complete profile for all relevant animal models in ASD research.Electronic supplementary materialThe online version of this article (10.1186/s13229-019-0263-7) contains supplementary material, which is available to authorized users.

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“…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.…”

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confidence: 99%

Human in vitro models for understanding mechanisms of autism spectrum disorder

Gordon

Geschwind

2020

Molecular Autism

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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

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Maternal cytomegalovirus sero‐positivity and autism symptoms in children

Abstract: Our results suggest that maternal CMV infections may influence ASD symptoms. These findings are being further evaluated in ongoing prospective studies with larger population samples.

Cited by 42 publications

References 46 publications

Review of Clinical Studies Targeting Inflammatory Pathways for Individuals With Autism

Review of Clinical Studies Targeting Inflammatory Pathways for Individuals With Autism

A multifaceted approach for analyzing complex phenotypic data in rodent models of autism

Human in vitro models for understanding mechanisms of autism spectrum disorder

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