title: Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.
abstract: Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California, Davis, Sacramento, CA, USA. mdbauman@ucdavis.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Bauman
authors.forename: A-M
authors.initials: AM
authors.lastname: Iosif
authors.forename: P
authors.initials: P
authors.lastname: Ashwood
authors.forename: D
authors.initials: D
authors.lastname: Braunschweig
authors.forename: A
authors.initials: A
authors.lastname: Lee
authors.forename: C M
authors.initials: CM
authors.lastname: Schumann
authors.forename: J
authors.initials: J
authors.lastname: Van de Water
authors.forename: D G
authors.initials: DG
authors.lastname: Amaral
mesh_terms: D000367:Age Factors; D000818:Animals; D001321:Autistic Disorder / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001921:Brain / Q000254:growth & development* / Q000276:immunology; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D059906:Neuroimaging; D011247:Pregnancy; D012919:Social Behavior
chemical_list: D001323:Autoantibodies; D009419:Nerve Tissue Proteins