title: Stereotypies and hyperactivity in rhesus monkeys exposed to IgG from mothers of children with autism.
abstract: Autism together with Asperger syndrome and pervasive developmental disorder not otherwise specified form a spectrum of conditions (autism spectrum disorders or ASD) that is characterized by disturbances in social behavior, impaired communication and the presence of stereotyped behaviors or circumscribed interests. Recent estimates indicate a prevalence of ASD of 1 per 150 (Kuehn, 2007). The cause(s) of most cases of ASD are unknown but there is an emerging consensus that ASD have multiple etiologies. One proposed cause of ASD is exposure of the fetal brain to maternal autoantibodies during pregnancy [Dalton, P., Deacon, R., Blamire, A., Pike, M., McKinlay, I., Stein, J., Styles, P., Vincent, A., 2003. Maternal neuronal antibodies associated with autism and a language disorder. Ann. Neurol. 53, 533-537]. To provide evidence for this hypothesis, four rhesus monkeys were exposed prenatally to human IgG collected from mothers of multiple children diagnosed with ASD. Four control rhesus monkeys were exposed to human IgG collected from mothers of multiple typically developing children. Five additional monkeys were untreated controls. Monkeys were observed in a variety of behavioral paradigms involving unique social situations. Behaviors were scored by trained observers and overall activity was monitored with actimeters. Rhesus monkeys gestationally exposed to IgG class antibodies from mothers of children with ASD consistently demonstrated increased whole-body stereotypies across multiple testing paradigms. These monkeys were also hyperactive compared to controls. Treatment with IgG purified from mothers of typically developing children did not induce stereotypical or hyperactive behaviors. These findings support the potential for an autoimmune etiology in a subgroup of patients with neurodevelopmental disorders. This research raises the prospect of prenatal evaluation for neurodevelopmental risk factors and the potential for preventative therapeutics.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, California National Primate Research Center and The MIND Institute, University of California-Davis, 2825 50th Street, Sacramento, CA 95817, USA.
authors.forename: Loren A
authors.initials: LA
authors.lastname: Martin
authors.forename: Paul
authors.initials: P
authors.lastname: Ashwood
authors.forename: Daniel
authors.initials: D
authors.lastname: Braunschweig
authors.forename: Maricel
authors.initials: M
authors.lastname: Cabanlit
authors.forename: Judy
authors.initials: J
authors.lastname: Van de Water
authors.forename: David G
authors.initials: DG
authors.lastname: Amaral
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001321:Autistic Disorder / Q000276:immunology*; D001522:Behavior, Animal / Q000187:drug effects; D002648:Child; D005260:Female; D006801:Humans; D006948:Hyperkinesis / Q000139:chemically induced / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000097:blood / Q000302:isolation & purification / Q000633:toxicity*; D008253:Macaca mulatta; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology* / Q000523:psychology; D012307:Risk Factors; D012919:Social Behavior; D013239:Stereotyped Behavior / Q000187:drug effects*
chemical_list: D007074:Immunoglobulin G