More than 250 years ago, Linnaeus observed changes in floral symmetry that were passed down through several generations. Two centuries later, it was discovered that this change was not due to a genetic mutation but rather to genetic regulation mediated by what has since been termed epigenesis—the factors that control the activation or inactivation of genes. This mechanism has since been shown to be ubiquitous across the entire animal kingdom and in humans. Furthermore, this mechanism is largely modulated by the environment, thereby serving as a major link between all internal and external environmental factors and the influence of genetic factors. This mechanism is passed down through several generations; for example, a mouse pup subjected to stress (separation from its mother for a few moments) passes on to its offspring a heightened response to stressors. In humans, a frequently cited example is that of a large part of the Netherlands (4 million people) that was besieged by the Nazis for several months without food. The children of pregnant women who gave birth during this period passed on, for generations, a high sensitivity to stress without any alteration to their DNA sequence. Similarly, in homozygous twins (who, in principle, have the same DNA), type 2 diabetes develops in both twins in only 50% of cases, underscoring the importance of the environment. Furthermore, mice born to a female mouse that was inseminated with sperm from mice fed a high-fat diet develop type 2 diabetes. The mechanisms are known and involve non-coding RNAs.
In the case of autism (and many other neurodevelopmental syndromes), a wealth of data suggests non-genomic changes—that is, changes not mediated by alterations in the DNA sequence—but rather changes in methylation, microRNA modifications, and other aspects of DNA structure. As I have emphasized in other writings (see my blog), this is particularly important in syndromes that “originate” in utero. Brain development from fertilization through birth is particularly fragile and susceptible to alterations, with a plethora of non-genetic factors—in the usual sense—intervening to modify the process, including internal environmental factors (hormones, stress, treatments, and comfort-inducing substances, etc.) that can impact the process.
In summary, it is impossible to view autism—like most brain disorders or syndromes—as resulting solely from genetic determinism that ignores environmental factors. With the exception of certain familial forms, the overwhelming majority of autism cases are “sporadic,” in which genes and environmental factors interact in complex ways.
