Autism is a neurodevelopmental disorder characterized by deficits in social behavior and communication and the presence of repetitive or stereotyped behaviors. The etiology(ies) of autism are currently unknown. However, evidence suggests that maternal autoantibodies directed against fetal brain tissue are a putative cause for a subset of autism cases. In support of this, we have recently identified a characteristic pattern of autoantibody production to human fetal brain tissue (and to rhesus monkey brain tissue) in 20% of mothers of multiple children with autism. Our preliminary studies indicate that rhesus monkeys, prenatally exposed to IgG class antibodies from these mothers, produce more whole body motor stereotypies (a defining symptom of autism) compared to control monkeys. These preliminary findings, while striking, are based on a small number of treated subjects, a restricted window of exposure to the purified IgG and a relatively limited period of behavioral observations. It is possible that extending the duration of IgG exposure may result in other behavioral abnormalities more indicative of the complete autistic syndrome. We propose to replicate and extend our research on this promising immunological model of autism by increasing the number of experimental subjects and increasing the duration of IgG exposure into the second trimester for a subset of the experimental subjects. We will enhance and extend the behavioral observations of the treated animals and carry out a structural neuroimaging study. We propose first to conduct an extensive behavioral assessment of the subjects during the first two years of development. We will quantitatively analyze the emergence of species typical behaviors in a variety of social contexts and in experiments designed to probe attachment, social dominance, social motivation and fear reactions. These studies will also evaluate the quality of transactional interactions and detect abnormal behaviors such as stereotypies. We will also carry out a detailed longitudinal magnetic resonance imaging (MRI) study to evaluate differences in the time course of brain development. We will focus the MRI analyses on brain regions most commonly implicated in the neuropathology of autism, including the frontal lobes, amygdala and cerebellum and on structures associated with stereotypies such as the basal ganglia. This work represents a promising animal model of autism and may have direct implications for diagnosis, prevention and treatment of this disorder.
Autism spectrum disorders affect 1:150 children in the United State though the cause(s) are unknown. This project is designed to provide additional support for the hypothesis that abnormal maternal autoantibodies may be one cause of autism. If maternal autoantibodies are identified as a risk factor for autism, this finding would quickly lead both to the development of a diagnostic assay for maternal autoantibodies and to the development of therapeutic interventions to diminish this autism risk factor.
| Bauman, M D; Iosif, A-M; Ashwood, P et al. (2013) Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey. Transl Psychiatry 3:e278 |
| Fox, Elizabeth; Amaral, David; Van de Water, Judy (2012) Maternal and fetal antibrain antibodies in development and disease. Dev Neurobiol 72:1327-34 |
