Elsevier

NeuroToxicology

Volume 29, Issue 3, May 2008, Pages 532-545
NeuroToxicology

Immunologic and neurodevelopmental susceptibilities of autism

https://doi.org/10.1016/j.neuro.2008.02.006Get rights and content

Abstract

Symposium 5 focused on research approaches that are aimed at understanding common patterns of immunological and neurological dysfunction contributing to neurodevelopmental disorders such as autism and ADHD. The session focused on genetic, epigenetic, and environmental factors that might act in concert to influence autism risk, severity and co-morbidities, and immunological and neurobiological targets as etiologic contributors. The immune system of children at risk of autism may be therefore especially susceptible to psychological stressors, exposure to chemical triggers, and infectious agents. Identifying early biomarkers of risk provides tangible approaches toward designing studies in animals and humans that yield a better understanding of environmental risk factors, and can help identify rational intervention strategies to mitigate these risks.

Section snippets

How can chemical exposure contribute to autism risk? I.N. Pessah, UC, Davis, CA, USA

Autism is a heterogeneous neurodevelopmental disorder defined by core deficits in social reciprocity, communication, and restrictive/repetitive patterns of interest and behavior (American Psychiatric Assoc, 2000). Although autism may be one of the most heritable complex disorders, the genes linked to autism risk do not segregate in a simple Mendelian manner (Folstein and Rosen-Sheidley, 2001, Trikalinos et al., 2005). There is increasing scientific interest in identifying complex interactions

Developmental neuroendocrine effects of polychlorinated biphenyls (PCBs): parallels with attention deficit hyperactivity disorder (ADHD). R.F. Seegal, Wadsworth Center, Albany, NY, USA

ADHD is the most commonly diagnosed neuropsychiatric/neurological disorder in children (McGough, 2005) and is characterized by behavioral hallmarks including attentional deficits, impulsivity and motor over-activity (Biederman, 2005, Himelstein et al., 2000). The incidence of this disorder ranges from 2 to 16% (Goldman et al., 1998), indicating the difficulties in diagnosis, the potential co-morbidity with other neuropsychiatric/neurological disorders and the likelihood that ADHD is a disorder

Polychlorinated biphenyls (PCBs) modulate the development of neuronal connectivity. Pamela J. Lein, CROET, Oregon Health & Science University, Portland, OR 97239, USA

PCBs are persistent widespread environmental contaminants, and high residue levels are still detected in human tissues (DeCaprio et al., 2005, Humphrey et al., 2000, Park et al., 2007). Epidemiological data indicate that PCBs negatively impact neuropsychological function in exposed children (Carpenter, 2006, Schantz et al., 2003), and experimental animal studies confirm that developmental PCB exposure causes cognitive and psychomotor deficits (Mariussen and Fonnum, 2006). PCBs disrupt thyroid

Epigenetic influences on autism risk: a role for GABAA receptor dysregulation. Janine M. LaSalle, University of California, Davis, CA 95616, USA

Epigenetics is the study of inheritable and reversible modifications to nucleotides or chromosomes that do not change the genetic sequence but can modify gene expression and phenotype. The importance of epigenetic mechanisms in regulating human brain development has been recently revealed by the discovery of the genetic bases of several human neurodevelopmental disorders (Egger et al., 2004, Hendrich and Bickmore, 2001, Zoghbi, 2003). Genetic syndromic causes of autism that involve epigenetic

The impacts of maternal immune challenge on the fetal brain and the pathological consequences on behavior. Benjamin K. Yee, Urs Meyer, and Joram Feldon, Laboratory of Behavioral Neurobiology, ETH Zurich, Switzerland

Maternal infection in prenatal life is a notable risk factor in the development of severe neuropsychiatric disorders in later life, including schizophrenia and autism (reviewed in Arndt et al., 2005, Brown, 2006, Brown and Susser, 2002, Fatemi, 2005, Patterson, 2007). One prevalent hypothesis suggests that infection-induced disruption of early prenatal brain development may predispose the organism for long-lasting structural and functional brain abnormalities, leading to the emergence of

Maternal autoantibodies: developmental neurotoxicants of autism risk? Judy Van de Water, University of California, Davis, CA 95616, USA

Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by impairments in social interaction, verbal and nonverbal communication, and stereotyped behaviors and interests (Lord et al., 2000a). ASD encompasses a broad range of phenotypes and diagnosis is currently based solely on behavioral criteria (Lord et al., 2000b). The etiology of ASD is not well understood, though it likely involves both genetic and environmental factors (Volkmar and Pauls, 2003). Although the age of

Examination of thimerosal effects in neonatal SJL/J mice at vaccination-associated exposure levels. Robert F. Berman, University of California, Davis, CA 95616, USA

Thimerosal (sodium ethyl mercury thiosalicylate) is an antimicrobial preservative used since the 1930s in numerous vaccines and medicinal preparations. Ethylmercury poisoning has occurred in humans, resulting in renal and neurotoxicity in the affected populations (Cinca et al., 1980, Damluji, 1962; Hilmy et al., 1976; Zhang, 1984). However, the possible effects of exposure to lower levels of ethyl mercury, such as those levels associated with immunization with thimerosal-preserved vaccines, are

Acknowledgements

The work presented was supported by USEPA grant R829390 and NIH grants ES010338, HD40936, ES11269, ES014901, ES015171, ES11263, HD40936.and GM041292, ETH Zurich, and The Swiss National Science Foundation.

References (210)

  • A.M. Connolly et al.

    Brain-derived neurotrophic factor and autoantibodies to neural antigens in sera of children with autistic spectrum disorders, Landau-Kleffner syndrome, and epilepsy

    Biol Psychiatry

    (2006)
  • C. Cunningham et al.

    The sickness behaviour and CNS inflammatory mediator profile induced by systemic challenge of mice with synthetic double-stranded RNA (poly I:C)

    Brain Behav Immun

    (2007)
  • E. Davids et al.

    Animal models of attention-deficit hyperactivity disorder

    Brain Res Rev

    (2003)
  • A.P. DeCaprio et al.

    Polychlorinated biphenyl (PCB) exposure assessment by multivariate statistical analysis of serum congener profiles in an adult Native American population

    Environ Res

    (2005)
  • A. Fiumara et al.

    Peripheral lymphocyte subsets and other immune aspects in Rett syndrome

    Pediatr Neurol

    (1999)
  • D.H. Geschwind et al.

    Autism spectrum disorders: developmental disconnection syndromes

    Curr Opin Neurobiol

    (2007)
  • J.H. Gilmore et al.

    Exposure to infection and brain development: cytokines in the pathogenesis of schizophrenia

    Schizophr Res

    (1997)
  • J.H. Gilmore et al.

    Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal–fetal unit of the rat

    J Neuroimmunol

    (2005)
  • J. Hany et al.

    Behavioral effects following single and combined maternal exposure to PCB 77 (3,4,3′,4′-tetrachlorobiphenyl) and PCB 47 (2,4,2′,4′- tetrachlorobiphenyl) in rats

    Neurotoxicol Teratol

    (1999)
  • G.J. Harry et al.

    Mercury concentrations in brain and kidney following ethylmercury, methylmercury and thimerosal administration to neonatal mice

    Toxicol Lett

    (2004)
  • S. Havarinasab et al.

    Immunosuppressive and autoimmune effects of thimerosal in mice

    Toxicol Appl Pharmacol

    (2005)
  • S. Havarinasab et al.

    Organic mercury compounds and autoimmunity

    Autoimmun Rev

    (2005)
  • P. Heiser et al.

    Molecular genetic aspects of attention-deficit/hyperactivity disorder

    Neurosci Biobehav Rev

    (2004)
  • A.S. Howard et al.

    Polychlorinated biphenyls induce caspase-dependent cell death in cultured embryonic rat hippocampal but not cortical neurons via activation of the ryanodine receptor

    Toxicol Appl Pharmacol

    (2003)
  • P. Hultman et al.

    Methyl mercury-induced autoimmunity in mice

    Toxicol Appl Pharmacol

    (1999)
  • P.R. Huttenlocher

    Dendritic and synaptic pathology in mental retardation

    Pediatr Neurol

    (1991)
  • J.L. Jacobson et al.

    Prenatal exposure to polychlorinated biphenyls and attention at school age

    J Pediatr

    (2003)
  • J.P. Kapfhammer

    Cellular and molecular control of dendritic growth and development of cerebellar Purkinje cells

    Prog Histochem Cytochem

    (2004)
  • J.F. Krey et al.

    Molecular mechanisms of autism: a possible role for Ca2+ signaling

    Curr Opin Neurobiol

    (2007)
  • L.J. Lawrence et al.

    Interactions of lindane, toxaphene and cyclodienes with brain-specific t-butylbicyclophosphorothionate receptor

    Life Sci

    (1984)
  • M.G. Aman et al.

    Pharmacotherapy for hyperactivity in children with autism and other pervasive developmental disorders

    J Autism Dev Disord

    (2000)
  • American Psychiatric Association

    Diagnostic and statistical manual of mental disorders DMS-IV-TR (text revision)

    (2000)
  • R.E. Amir et al.

    Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- CpG-binding protein 2

    Nat Genet

    (1999)
  • A.E. Ashley-Koch et al.

    An analysis paradigm for investigating multi-locus effects in complex disease: examination of three GABA receptor subunit genes on 15q11-q13 as risk factors for autistic disorder

    Ann Hum Genet

    (2006)
  • P. Ashwood et al.

    The immune response in autism: a new frontier for autism research

    J Leukoc Biol

    (2006)
  • E. Ausó et al.

    A moderate and transient deficiency of maternal thyroid function at the beginning of fetal neocorticogenesis alters neuronal migration

    Endocrinology

    (2004)
  • A. Bailey et al.

    Autism as a strongly genetic disorder: evidence from a British twin study

    Psychol Med

    (1995)
  • S. Barone et al.

    Vulnerable processes of nervous system development: a review of markers and methods

    Neurotoxicology

    (2000)
  • M.K. Belmonte et al.

    Fragile X syndrome and autism at the intersection of genetic and neural networks

    Nat Neurosci

    (2006)
  • J.C. Bemis et al.

    PCB-induced inhibition of the vesicular monoamine transporter predicts reductions in synaptosomal dopamine content

    Toxicol Sci

    (2004)
  • R.F. Berman et al.

    Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice

    Toxicol Sci

    (2008)
  • S. Bernard et al.

    The role of mercury in the pathogenesis of autism

    Mol Psychiatry

    (2002)
  • D.C. Bittel et al.

    Microarray analysis of gene/transcript expression in Prader-Willi syndrome: deletion versus UPD

    J Med Genet

    (2003)
  • J.R. Bloomquist

    Chloride channels as tools for developing selective insecticides

    Arch Insect Biochem Physiol

    (2003)
  • A.S. Brown

    Prenatal infection as a risk factor for schizophrenia

    Schizophr Bull

    (2006)
  • A.S. Brown et al.

    In utero infection and adult schizophrenia

    Ment Retard Dev Disabil Res Rev

    (2002)
  • H. Brunn et al.

    Polychlorinated biphenyls (PCB) in human adipose tissue

    Z Lebensm Unters Forsch

    (1990)
  • T.M. Burbacher et al.

    Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal

    Environ Health Perspect

    (2005)
  • J.D. Buxbaum et al.

    Association between a GABRB3 polymorphism and autism

    Mol Psychiatry

    (2002)
  • M. Cabanlit et al.

    Brain-specific autoantibodies in the plasma of subjects with autistic spectrum disorder

    Ann NY Acad Sci

    (2007)
  • Cited by (0)

    View full text