Environmental Factors and Limbic Vulnerability in Childhood Autism

The rise in prevalence of autism spectrum disorders (ASD) is suggestive of a new etiology. Diagnostic substitution alone is unlikely to account for the increase, while genetic association with detoxification gene alleles points to an environmental contribution. Subtle structural anomalies in the ASD brain are widespread but limbic damage seems important for the development of behaviors diagnostic of ASD. The limbic brain is especially susceptible to environmental challenge: internal sensing, physiological feedback and neuroinflammatory processes may underlie this sensitivity to insult. Primary damage leading to ASD in later life is likely to take place in utero and/or in the immediate postnatal period. Despite evidence of heavy metal involvement, a causal connection may not yet be concluded because subjects exposed to metals tend to be exposed to other environmental agents. Because maternal minerals and lipids are supplied to the unborn child, historic toxic exposure of the mother may be pivotal. A two-hit combination of genetic susceptibility and environmental challenge is argued to underlie the rise in ASD.