Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Ravaccia, Davide; Ghafourian, Taravat

doi:10.3390/biomedicines8120557

Cited by 24 publications

(20 citation statements)

References 143 publications

(268 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Early epidemiological studies produced conflicting results, but later studies focussed on serologically confirmed influenza cases using serum antibodies or other markers of inflammation and have provided additional evidence for maternal inflammation during development as a risk factor for schizophrenia ( Brown et al., 2004 ; Ellman and Susser, 2009 ; Scola and Duong, 2017 ). Similar associations have been described for autism risk ( Atladóttir et al., 2010 ; Jiang et al., 2016 ; Lee et al., 2015 ; Ornoy et al., 2015 ; Patterson, 2011 ; Ravaccia and Ghafourian, 2020 ; Zerbo et al., 2015 ). Whether a similar increase in neurodevelopmental diseases will occur in the years following SARS-CoV-2 emergence remains to be seen.…”

Section: Introductionsupporting

confidence: 80%

Maternal immune activation as a risk factor for psychiatric illness in the context of the SARS-CoV-2 pandemic

Lins

2021

Brain, Behavior, & Immunity - Health

View full text Add to dashboard Cite

Inflammation, due to infectious pathogens or other non-infectious stimuli, during pregnancy is associated with elevated risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. Although historically identified through retrospective epidemiologic studies, the relationship between maternal immune activation and offspring neurodevelopmental disease risk is now well established because of clinical studies which utilized prospective birth cohorts, serologically confirmed infection records, and subsequent long-term offspring follow-up. These efforts have been corroborated by preclinical research which demonstrates anatomical, biochemical, and behavioural alterations that resemble the clinical features of psychiatric illnesses. Intervention studies further demonstrate causal roles of inflammatory mediators, such as cytokines, in these long-lasting changes in behaviour and brain. This review summarizes a selection of maternal immune activation literature that explores the relationship between these inflammatory mediators and the neuropsychiatric-like effects later observed in the offspring. This literature is presented alongside emerging information regarding SARS-CoV-2 infection in pregnancy, with discussion of how these data may inform future research regarding the effects of the present coronavirus pandemic on emerging birth cohorts.

show abstract

Section: Introductionsupporting

confidence: 80%

Maternal immune activation as a risk factor for psychiatric illness in the context of the SARS-CoV-2 pandemic

Lins

2021

Brain, Behavior, & Immunity - Health

View full text Add to dashboard Cite

show abstract

“…Comorbidity of two or more of these disorders is observed at rates higher than what it would be expected by chance, suggesting the existence of clusters of shared biological mechanisms ( 3 , 4 ). While cooccurrence of neurological features and conditions is frequently observed, very often, NDDs also include a variety of extra-neurological clinical signs such as hypotonia, dysmorphology, cardiologic or metabolic features, as well as gastrological problems such as constipation or diarrhea, which are specially frequent in ASD and ADHD ( 5 – 7 ), or immunological abnormalities ( 8 , 9 ). The recent advances in genotyping and sequencing technologies have propelled the identification of risk/causal genes, which has pointed to remarkable genetic heterogeneity among and within specific NDDs; for intellectual disability alone, pathogenic mutations in more than 1,000 genes have been confirmed in the SysID database (a systematic and manually curated catalog of ID-associated genes) ( 10 ).…”

Section: Introduction: Heterogeneity Beyond Idiopathic Neurodevelopmental Disordersmentioning

confidence: 99%

Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments

Verdura¹,

Pérez-Cano²,

Sabido-Vera³

et al. 2021

Front. Psychiatry

View full text Add to dashboard Cite

Fragile X syndrome (FXS) is the most frequent monogenic cause of autism or intellectual disability, and research on its pathogenetic mechanisms has provided important insights on this neurodevelopmental condition. Nevertheless, after 30 years of intense research, efforts to develop treatments have been mostly unsuccessful. The aim of this review is to compile evidence from existing research pointing to clinical, genetic, and therapeutic response heterogeneity in FXS and highlight the need of implementing precision medicine-based treatments. We comment on the high genetic and phenotypic heterogeneity present in FXS, as a contributing factor to the difficulties found during drug development. Given that several clinical trials have showed a non-negligeable fraction of positive responders to drugs targeting core FXS symptoms, we propose that success of clinical trials can be achieved by tackling the underlying heterogeneity in FXS by accurately stratifying patients into drug-responder subpopulations. These precision medicine-based approaches, which can be first applied to well-defined monogenic diseases such as FXS, can also serve to define drug responder profiles based on specific biomarkers or phenotypic features that can associate patients with different genetic backgrounds to a same candidate drug, thus repositioning a same drug for a larger number of patients with NDDs.

show abstract

“…Maternal immune activation during pregnancy has also been comprehensively researched in order to better understand potential etiologies of autism. Infectious outbreaks, particularly the Rubella outbreak of the 1960s, provided substantial evidence that supported maternal immune activation as a risk factor for autism, proving that the disease caused but Rubella virus (and not the vaccine) is directly causing significant brain damage resulting in intellectual disability, autism and blindness [ 37 , 38 ]. Rubella infection is a hallmark of viral infection causing brain damage in the fetus and subsequent neurodevelopmental impairments including intellectual disability and autism.…”

Section: Immune System In Autismmentioning

confidence: 99%

The myth of vaccination and autism spectrum

Gabis

Attia

Goldman

et al. 2022

European Journal of Paediatric Neurology

View full text Add to dashboard Cite

Background Among all of the studied potential causes of autism, vaccines have received some of the most scrutiny and have been the topic of many evidence-based studies. These efforts have led the great majority of scientists, physicians, and public health researchers to refute causation between vaccines and autism. Rationale This presumed association and concern has been a major contributor to parents’ refusal to immunize their children and has become a major threat to public health in secluded populations over the last two decades, even prior to the COVID-19 pandemic. With the emergence of COVID-19 immunizations, sentiments towards this topic were addressed as a public health concern that may influence the ability to overcome the Corona virus worldwide. Scientific review of data Despite the overwhelming data demonstrating that there is no link between vaccines and autism, many parents are hesitant to immunize their children because of the alleged association. Other contributing factors to the myths and conspiracy theories surrounding the association between vaccines and autism include the fact that the diagnosis of autism is typically made after the age of receiving the main childhood immunizations, as well as the occasional occurrence of regression after the age of first year vaccinations. In spite of vast evidence that the main contribution to the increase in incidence is from improvement of the diagnostic process, this rapid and publicized rise in autism diagnoses feeds parental concerns regarding any medical intervention that may be associated with the health of their children. Recommandations It is plausible that with more evidence-based studies linking autism to specific etiologies the myth will diminish and disappear eventually. In an era where conspiracy theories are prevalent on social media, it is critical that evidence-based studies relating autism to specific etiologies be made public, and that information concerning autism diagnosis and causes be made more readily available through social media and parental organizations.

show abstract

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Cited by 24 publications

References 143 publications

Maternal immune activation as a risk factor for psychiatric illness in the context of the SARS-CoV-2 pandemic

Maternal immune activation as a risk factor for psychiatric illness in the context of the SARS-CoV-2 pandemic

Heterogeneity in Fragile X Syndrome Highlights the Need for Precision Medicine-Based Treatments

The myth of vaccination and autism spectrum

Contact Info

Product

Resources

About