Prenatal influences on brain dopamine and their relevance to the rising incidence of autism.

The incidence of autism has risen 10-fold since the early 1980s, with most of this rise not explainable by changing diagnostic criteria. The rise in autism is paradoxical in that autism is considered to be one of the most genetically determined of the major neurodevelopmental disorders and should accordingly either be stable or even declining. Because a variety of epigenetic influences, particularly those occurring during the prenatal period, can override or masquerade as genetic influences, these should be considered as prime contributors to the recent increase of autism. Prenatal influences on dopamine activity are especially well-documented, including the effects of maternal psychosocial stress, maternal fever, maternal genetic and hormonal status, use of certain medications, urban birth, and fetal hypoxia. All of these factors have been implicated in the genesis of autism, which is characterized by a "hyperdopaminergic" state based on evidence from monkey and human behavioral studies, pharmacological studies in humans, and a left-hemispheric predominance of both dopamine and autistic-like symptoms. Chronically high maternal levels of dopamine caused by the pressures of increasingly urbanized societies and by changing maternal demographics such as increased workforce participation, educational achievement level, and age at first birth, may be especially significant epigenetic contributors to the recent autism rise.