Where Is the Discussion About Choline and Fetal Alcohol Exposure?

To the Editor: We read with great interest the Review and Overview article by Wakschlag et al. (1), published in the February 2018 issue of the Journal, on the neurodevelopmental basis of early childhood disruptive behavior. Naturally, we thought the idea of developing a clear picture of the phenotype that can be identified in early childhood is outstanding because it would allow for early detection and strengthening the environment to help such patients and could also be used for prevention. The authors’ notion of defining the neurodevelopment in early childhood by using irritability and callous behavior to measure these characteristics was very well crafted.

The question is: Where is the variable of exposure to fetal alcohol in the article’s consideration of emotional regulation? It strikes one that clinically, emotional dysregulation characteristic of children who have been exposed to fetal alcohol is similar to irritability and callousness, so we were wondering if that was a consideration in the study. The authors appropriately note the role of the dorsolateral prefrontal cortex and its function in the reward process. However, a deeper look suggests the uncinate fasciculus plays a role in the process of reward and punishment as well and may regulate emotional control by applying brakes to the limbic system (2).

When we wrote Dr. Randal G. Ross about the prevalence of fetal alcohol exposure and whether the problems of choline deficiency as caused by fetal alcohol exposure might provide answers to this team’s work essentially involving choline supplementation to pregnant women (3), he wrote back asking what the mechanism might be, but we did not have a clear hypothesis until now. The affect dysregulation (which may be similar to irritability and callousness) seen in the article by Hagan et al. (4) could be either the lack of epigenetic methylation from the absence of choline or poor fetal neuronal migration of the cells of the dorsolateral prefrontal cortex or uncinate fasciculus or both.

Accordingly, could the authors instruct us about where fetal alcohol exposure fits into their marvelous article?