Autism is extremely heterogeneous. It is shaped by a complex interplay of genetic and environmental factors, which have been studied for decades, making RFK Jr’s pledge to determine “what has caused the autism epidemic” by September highly questionable. Some worry that the effort will be biased towards vaccine-autism theories, which have been repeatedly and thoroughly debunked. The strongest known contributors to autism risk are genetic, but there is reasonable evidence that environmental factors during pregnancy can affect autism risk in offspring (and, of course, these factors may interact with genetic predispositions). For example, activation of the mother’s immune system during pregnancy has been linked to increased autism risk. Proving causation in humans is tricky, so much of the evidence on this “maternal immune activation” comes from animal models. A recent preprint sheds light on the potential molecular mechanisms, suggesting that changes in DNA methylation disrupt neural circuit formation in the offspring of mice treated with a viral mimetic (poly(I:C), or PIC) during pregnancy.
The authors are careful to make the distinction between the immune activation in their experiments and the immune activation occurring upon mild infection or vaccination: “The cytokine levels post-PIC injection are comparable to those produced during a cytokine storm due to influenza or other serious infections. Such levels of proinflammatory cytokines are not produced during common cold infections or after immunizations.” So, if anything, vaccines before and during pregnancy might reduce autism risk by protecting against serious infections.
Maternal Immune Activation Disrupts Epigenomic and Functional Maturation of Cortical Excitatory Neurons
In bioRxiv, 29 April 2025
From the groups of Margarita Behrens, Eran Mukamel, and Joseph Ecker
Snippet by Katrina Woolcock
Image credit: Figure 1 from Lai et al. linked above (CC-BY-NC-ND)