Because of the variety of deficits that occur with FASD it can be hard to pinpoint the structural and functional changes that occur in the developing CNS and to identify how they relate to a particular behavioral disorder. Multiple brain regions are affected, and the areas and extent of damage depend on the amount and timing of ethanol ingestion. A number of molecular mechanisms may play a role, and these may be activated at different stages of development or at different dose thresholds of exposure [see Ref. (24, 25) for review]. These include disrupted cell energetics (26–30); cell cycle interference, and a deregulation of developmental timing (31–35); alterations in retinoic acid signaling (36); interference with cell and growth factor signaling (37–39); and apoptosis (38, 40, 41). Furthermore, many neurotransmitters, adhesive molecules, transcription factors, and trophic factors can be either up- or down-regulated by PNEE, making FASD a very complex syndrome [see Ref. (24) for review].
