International Meeting for Autism Research (London, May 15-17, 2008): Pediatric Vaccines Influence Primate Behavior, and Brain Stem Volume and Opioid Ligand Binding
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Pediatric Vaccines Influence Primate Behavior, and Brain Stem Volume and Opioid Ligand Binding

Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
A. Wakefield , Thoughtful House Center for Children, Austin, TX
C. Stott , Thoughtful House Center for Children, Austin, TX
B. Lopresti , Radiology, University of Pittsburgh, Pittsburgh, PA
J. Tomko , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA
L. Houser , Pittsburgh Development Center, University of Pittsburgh, Pittsburgh, PA
G. Sackett , Psychology, Washington National Primate Research Center, Seattle, WA
L. Hewitson , Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, PA
Background:

Abnormal brainstem structure and function have been reported in children with autism. Opioid receptors play key roles in neuro-ontogeny, are present in brainstem nuclei, and may influence aspects of autism. Childhood vaccines are a possible causal factor in autism and while primates are used in pre-clinical vaccine safety testing, the recommended infant regimen (1994-1999) has not been tested.

Objectives:

The objective of this study was to compare brain stem volume and opioid binding in rhesus infants receiving the recommended infant vaccine regimen.

Methods:

Rhesus macaques were administered vaccines adjusted for age and thimerosal dose (exposed; N=13), or placebo (unexposed; N=3) from birth onwards. Brainstem volume was measured by quantitative MRI, and binding of the non-selective opioid antagonist [11C]diprenorphine (DPN) was measured by PET, at 2 (T1) and 4 (T2) months of age. Neonatal reflexes and sensorimotor responses were measured in standardized tests for 30 days.

Results:

Kaplan-Meier survival analyses revealed significant differences between exposed and unexposed animals, with delayed acquisition of root, suck, clasp hand, and clasp foot reflexes. Interaction models examined possible relationships between time-to-acquisition of reflexes, exposure, [3C]DPN binding, and volume. Statistically significant interactions between exposure and time-to–acquisition of reflex on overall levels of binding at T1 and T2 were observed for all 18 reflexes. For all but one (snout), this involved a mean increase in time-to-acquisition of the reflex for exposed animals. In each model there was also a significant interaction between exposure and MRI volume on overall binding.

Conclusions:

This animal model examines the neurological consequences of the childhood vaccine regimen. Functional and neuromorphometric brainstem anomalies were evident in vaccinated animals that may be relevant to some aspects of autism. The findings raise important safety issues while providing a potential animal model for examining aspects of causation and disease pathogenesis in acquired neurodevelopmental disorders.

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