Autistic disorder and viral infections

Abstract

Autistic disorder (autism) is a behaviorally defined developmental disorder with a wide range of behaviors. Although the etiology of autism is unknown, data suggest that autism results from multiple etiologies with both genetic and environmental contributions, which may explain the spectrum of behaviors seen in this disorder. One proposed etiology for autism is viral infection very early in development. The mechanism, by which viral infection may lead to autism, be it through direct infection of the central nervous system (CNS), through infection elsewhere in the body acting as a trigger for disease in the CNS, through alteration of the immune response of the mother or offspring, or through a combination of these, is not yet known. Animal models in which early viral infection results in behavioral changes later in life include the influenza virus model in pregnant mice and the Borna disease virus model in newborn Lewis rats. Many studies over the years have presented evidence both for and against the association of autism with various viral infections. The best association to date has been made between congenital rubella and autism; however, members of the herpes virus family may also have a role in autism. Recently, controversy has arisen as to the involvement of measles virus and/or the measles, mumps, rubella (MMR) vaccine in the development of autism. Biological assays lend support to the association between measles virus or MMR and autism whereas epidemiologic studies show no association between MMR and autism. Further research is needed to clarify both the mechanisms whereby viral infection early in development may lead to autism and the possible involvement of the MMR vaccine in the development of autism.

Advances in behavioral genetics: mouse models of autism

“…242 The detrimental neurodevelopmental effects of maternal infection have been attributed, in part, to the induction of inflammatory cytokines. 243 Mouse models for prenatal exposure to maternal infection or inflammation have shown that the challenged offspring demonstrate an altered behavioral phenotype, including deficiencies in social interaction, exploration and sensorimotor gating. [244][245][246] Following maternal challenge with influenza virus, offspring also demonstrate altered gene expression in brain, including genes related to transcription and neurotransmission.…”

Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling

“…3 Epidemiological studies have indicated that maternal infections during pregnancy increase the risk for these disorders in the offspring. [4][5][6][7] According to one hypothesis, the maternal cytokine response to infections may play a crucial role in this association, 8 because the induction of cytokines is a fundamental immunological event triggered by virtually any infection. 9 More specifically, it has been suggested that activation of pro-inflammatory cytokines, including interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNF)-a, mediate the neurodevelopmental effects of maternal infections on the offspring.…”

The Role of the Immune System in Autism Spectrum Disorder

“…Varying reports have also implicated measles and mumps (Deykin and MacMahon, 1979), cytomegalovirus (Libbey et al, 2005), polyomaviruses (Lintas et al, 2010), and influenza (Atladottir et al, 2012;Deykin and MacMahon, 1979;Shi et al, 2003;Zhang et al, 2010) in the incidence of ASD. Some studies suggest fever as a correlate (Atladottir et al, 2012), with this risk potentially tempered by anti-fever medications, such as Advil, Tylenol, or Nyquil (Zerbo et al, 2013).…”

“…Given the diversity of infections that show a connection to the spectrum of autism disorders (Boksa, 2010;Libbey et al, 2005), as well as evidence from MIA models that reaction to infection rather than infection itself may lead to autismrelated symptoms (Shi et al, 2003), a possible common etiology may be the influence of the immune system (Gottfried et al, 2015;Lintas et al, 2010;Zhang et al, 2010). Cytokines, small cell-signaling proteins that act as immunomodulatory and endocrine messengers, have been implicated throughout the process of CNS development (Boulanger, 2009;Jones and Thomsen, 2013).…”