Importance of a Pathophysiological Foundation To Environmental Research In Autism: On Thimerosal, Vaccines, and More

In recent years, environmental factors have been increasingly perceived as potential contributors to the pathogenesis of autism. On one hand, this has spurred a constructive interest into gene-environment interaction models, yielding a significant amount of experimental and epidemiological data. On the other hand, an oversimplified and at times biased dissemination of these findings has generated misunderstandings, if not even waves of public alarm. For this reason, we emphasize the need for a strong, biologically-based pathophysiological foundation to investigations aimed at elucidating environmental contributions to complex disorders. First, we shall summarize the results of post-mortem brain studies in autism clearly supporting a prenatal origin for this disease. We shall then apply this knowledge to postnatal environmental factors claimed to be involved in autism pathogenesis, focussing on thimerosal and vaccinations. Thimerosal, an ethyl-mercury compound used as a preservative in vaccines, has drawn attention following initial anedoctal reports by some parents linking vaccinations to behavioral regression and to the onset of autism in their child within a matter of days or few weeks. Large retrospective epidemiological studies have excluded that thimerosal may cause autism, or provide large-scale contributions to its development. We shall present results suggesting that thimerosal, through its Ca²⁺-mobilizing effect, could conceivably precipitate an abrupt onset in a subset of children who would have anyway developed autistic symptoms, but perhaps more insidiously. Similarly, we shall summarize current data from our group and from others pointing toward analogous roles for vaccine-triggered immune responses, based on current evidence of an ongoing dysreactive autoimmune process in autistic patients. In either case, only evidence-based gene-environment interaction models will be presented, their strengths and limitations will be discussed, and the pathophysiological foundation of candidate environmental pathogens will be elucidated.