E.L. Williams, M.F. Casanova (contact), Department of Psychiatry and Behavioral Sciences, University of Louisville, Louisville, KY, USA. Medical Hypotheses. Volume 75, Issue 1, Pages 53-58 (July 2010)
The observable expression of autism, according to the Triple Hit Hypothesis, is determined by three factors: a developmental time window of vulnerability, genetic susceptibility, and environmental stressors. In utero exposure to thalidomide, valproic acid, and maternal infections are examples of some of the teratogenic (disturbance to fetal-development) agents which increase the risk of developing autism and define a time window of vulnerability. An additional stressor to genetically susceptible individuals during this time window of vulnerability may be prenatal ultrasound. Ultrasound enhances the genesis and differentiation of progenitor cells by activating the nitric oxide (NO) pathway and related neurotrophins. The effects of this pathway activation, however, are determined by the stage of development of the target cells, local concentrations of NO, and the position of nuclei (basal versus apical). Thereby causing consequent proliferation at some stages while driving differentiation and migration at others. Ill-timed activation or overactivation of this pathway by ultrasound may extend proliferation, increasing total cell number, and/or may trigger precipitous migration, causing maldistribution of neurons. The rising rates of autism coincident with the increased use of ultrasound in obstetrics and its teratogenic/toxic effects on the central nervous system demand further research.
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