AUTISM SPECTRUM DISORDERS AND INFECTIONS

Verrotti A, Conti P. Autism spectrum disorders and infections. International Journal of Infection. 2025;9(2):42-44.

A. Verrotti^1* and P. Conti²

¹ Department of Pediatrics, University of Perugia, Perugia, Italy;
² Postgraduate Medical School, University of Chieti-Pescara, Chieti, Italy.

*Correspondence to:
Prof. Alberto Verrotti,
Department of Pediatrics,
University of Perugia,
Perugia, Italy.
e-mail: alberto.verrotti@unipg.it

ABSTRACT

Autism Spectrum Disorder (ASD) is a multifactorial childhood disorder in which genetic, epigenetic, environmental, and immunological components play a crucial role. The possible connection between infections and autism has recently been explored. Studies have focused on cellular and molecular mechanisms involving neurobiology, the immune response, and inflammation. Maternal viral or bacterial infections during pregnancy can activate a systemic immune response with the production of pro-inflammatory cytokines, which cross the newborn’s immature blood-brain barrier and can cause brain damage. Alterations can occur in neuronal migration, synaptogenesis, and myelination, with changes in brain architecture associated with autism spectrum disorders. Neuroinflammation can negatively affect synaptic plasticity and neuronal function. Microorganisms can activate microglia, which produce pro-inflammatory cytokines and chemokines, counteracting the disease.

KEYWORDS: Autism spectrum disorder, infection, neurobiology, inflammation, neurodevelopment

INTRODUCTION

Autism spectrum disorder (ASD) is a varied group of neurodevelopmental conditions characterized by impaired social interaction and communication and restricted and repetitive behavior (1). Today, the Center for Disease Control and Prevention estimates that 1 out of every 110 children in America are diagnosed with ASD, and there has been an impressive rise in ASD in the last century (2). Children with ASD show complex developmental abnormalities defined on the basis of the severity of symptoms, particularly in language, socialization, learning, and stereotypical behaviors. About 30% of ASD children show sudden clinical regression at around 3 years of age. After much research by multiple large studies into the pathogenesis of this disease, it is now clear that vaccines do not cause autism. In addition, there is no single pathogen known to cause ASD and it is likely that the disease is due to a combination of different factors (3). In recent years, there has been a growing interest in the relationship between ASD and infections in general (4).

DISCUSSION

Infections can have a major impact on neurodevelopment, especially in the embryonic period and early childhood. However, studies are still unraveling the complexities of this association. It is likely that there are possible connections between infections and ASD. For example, maternal infections in the prenatal period during pregnancy have been associated with an increased risk of ASD in the child.

There are various pathogens that may contribute to the risk of ASD. For instance, congenital rubella syndrome, caused by rubella infection during pregnancy, can lead to developmental problems and ASD behaviors. Another infectious agent, cytomegalovirus (CMV), has been associated with neurological disorders, including ASD (5). Cases of influenza and fever during pregnancy, especially in the early months, can activate the maternal immune system against the fetus and increase the risk of ASD.

The mechanisms of maternal immune and inflammatory responses that alter physiological brain function are not yet clear. However, in vitro and ex vivo experiments on the brains of deceased autistic children (samples provided by the NIH), have demonstrated that pro- and anti-inflammatory cytokines are involved in ASD (6). Pro-inflammatory cytokines are produced by microglia activated by a putative antigen that could also be a microbial agent, which could pass the blood-brain barrier (BBB) that is not yet fully formed in the child. Therefore, inflammatory cytokines could damage the brain tissue still in development.

Herpes viruses and enteroviruses have been implicated in the development of ASD following postnatal infections, especially in the first period of life when the BBB is not yet formed. Alterations of the gut microbiota due to infections could also influence the gut-brain axis and modify children’s behavior (7).  Dysregulation of the immune system in the child, such as autoantibodies directed against brain tissue with activation of the autoimmune response, could also contribute to the development of ASD (8). Thus, infections may impact neurodevelopment, interfering with neuronal proliferation and migration, sympathetic development, and microglia activation, all of which are phenomena that are found in ASD.

However, it is possible that infections by microorganisms alone are not sufficient to cause ASD but may interact with genetic susceptibility. For example, a child with mutations in sympathetic genes may be more vulnerable to the effects of maternal infection or immune activation. However, there is no direct evidence on the specificity of infections associated with ASD. It is likely that targeted clinical trials on specific anti-inflammatory or immunomodulatory treatments may help in understanding this serious pathology (9).

CONCLUSIONS

ASD is a neurological disorder that still raises many questions regarding its diagnosis and treatment. Recent studies have highlighted how certain maternal infections during pregnancy may cause ASD. Cytokine activation by microorganisms, which cross the BBB, can cause neuronal damage and could induce ASD. There is no single microorganism that can cause ASD, and this serious brain disorder is likely due to a combination of factors. Additionally, it is now certain that vaccines do not cause autism, as this has been widely disproved by numerous international studies. Because the pathogenesis of this disorder is completely unknown, further studies are needed to clarify this enigma.

Conflict of interest

The authors declare that they have no conflict of interest.

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