IMFAR 2012 – MIND Institute UC Davis – Research

Investigation of Vocalization and Play Behavior in Juvenile Offspring of Maternal Immune Activated Female Mice

Results: Offspring of females exposed to Poly(I:C) exhibited increased frequency of vocalizations on postnatal day 10 of development. Interestingly, pups from immune activated females displayed alterations in social interaction during juvenile play with a novel mouse.

Conclusions: Maternal immune activation on gestational day 12.5 results in altered patterns of ultrasonic vocalizations and juvenile interactions in offspring. These findings support the link between maternal infection and increased prevalence of autism.

Immune Dysfunction in Fragile X Syndrome and Autism

Objectives:  In order to ascertain if immune dysregulation is present in children with FXS, dynamic cellular responses to immune stimulation were determined.

Conclusions:  These findings suggest that dynamic cellular responses in children with FXS exhibit a skew towards a TH2 cytokine profile when compared with controls. These findings support previous observations of TH2 cytokines profiles in the plasma of children with FXS. Further evaluation of TH2 cytokine profiles in FXS is warranted to delineate immune alteration in FXS with and without the occurrence of ASD in this disorder.

Maternal Immune-Mediated Conditions in Association with Child Immune-Related Outcomes and Autism Spectrum Disorders

Objectives: We sought to determine whether maternal autoimmune disease, asthma, and allergies influenced whether there were immune-related subphenotypes (specifically, gastrointestinal diagnoses, asthma, and allergies) in the child with autism, and whether these maternal immune-mediated conditions affected child scores on cognitive and behavioral tests.

Conclusions: Our results suggest that maternal immune-mediated conditions may account for some of the phenotypic variability within ASD, and point to the importance of the maternal immune response in affecting neurodevelopmental outcomes. In particular, case children whose mothers have an autoimmune disease may be at greater risk for GI diagnosis relative to those children whose mothers do not have such conditions.

The Presence of Specific Maternal IgG Antibodies Is Associated with Abnormal Brain Enlargement in ASD and in Nonhuman Primate Model of ASD

Objectives: We evaluated children born to mothers with these autism-specific IgG autoantibodies to determine whether they exhibit a distinct neural phenotype.  In a parallel line of research utilizing nonhuman primates, we evaluated brain and behavioral development of rhesus monkeys prenatally exposed to these autism-specific antibodies.

These results suggest that there may be an underlying immunological etiology for megalencephaly/macrocephaly in autism. With the nonhuman primate model, we will be able to evaluate the cellular/molecular pathology associated with this pattern of abnormal brain growth. The translational nature of this multidisciplinary research can be used to further determine the pathological significance of the autism-specific antibodies, and may ultimately contribute to novel preventative and/or therapeutic measures.

Asthma and Allergies in Children with Autism Spectrum Disorders

Objectives: We sought to determine whether 1) child asthma and allergies are more common in children with autism spectrum disorder (ASD) and 2) whether asthma and allergies are associated with other subphenotypes within autism

Conclusions: Our results suggest that asthma and allergies are not more common in young children with autism spectrum disorder, and that the presence of these conditions does not significantly affect cognitive and behavioral scores. However, future work should further assess the preliminary association we saw with a tendency for higher stereotypy scores in case children with allergies.

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