The issue of autism prevalence gained significant attention this week after President Donald Trump, speaking at a White House press event, claimed that taking Tylenol during pregnancy was linked to an increased risk of autism in children.
“The Trump Administration does not believe popping more pills is always the answer for better health,” White House Press Secretary Karoline Leavitt said in a follow-up statement. “There is mounting evidence finding a connection between acetaminophen use during pregnancy and autism — and that’s why the Administration is courageously issuing this new health guidance.”
The remarks sparked swift backlash from healthcare experts, who emphasized that no scientific study has ever established a causal link between Tylenol use and autism.
Yet, as debates over modern medicine dominate the headlines, new research suggests the roots of autism’s high prevalence in humans may trace back much further—embedded deep in the evolutionary history of the human brain.
In a recent study published in Molecular Biology and Evolution, researchers from Stanford University report that a specific type of brain cell, known as layer 2/3 intratelencephalic (L2/3 IT) neurons, has undergone accelerated evolutionary changes in humans compared to other primates.
Researchers assert that these changes appear tied to a dramatic down-regulation of genes associated with autism, pointing to natural selection as a possible driver of both human intelligence and heightened autism susceptibility.
“Surprisingly, this accelerated evolution was accompanied by the dramatic down-regulation of autism-associated genes, which was likely driven by polygenic positive selection specific to the human lineage,” the researchers write. “In summary, we introduce a general principle governing neuronal evolution and suggest that the exceptionally high prevalence of autism in humans may be a direct result of natural selection for lower expression of a suite of genes that conferred a fitness benefit to our ancestors while also rendering an abundant class of neurons more sensitive to perturbation.”
The study builds on a longstanding puzzle in evolutionary biology: why some cell types remain conserved across species, while others evolve more rapidly.
By analyzing more than a million neurons across six mammalian species, the researchers found a clear pattern—abundant neuronal types tend to evolve more slowly, while rarer ones change more quickly.
In humans, the opposite pattern emerged for L2/3 IT neurons, which are not only highly abundant but also central to complex thought, language, and abstract reasoning. Instead of remaining conserved, these neurons showed accelerated changes in gene expression.
However, the study found that the same changes that boosted human cognition may have come with a cost. L2/3 IT neurons in humans displayed significantly reduced expression of high-confidence autism-linked genes compared to chimpanzees and gorillas
This suggests that natural selection favored these genetic shifts, perhaps because they enhanced uniquely human traits, while simultaneously bringing humans closer to what the authors call an “ASD expression threshold,” where even minor genetic or environmental disruptions can push brain development into autism.
One striking example is the gene DLG4, which encodes the synaptic protein PSD-95. Researchers found that DLG4 expression in humans is 2.5 times lower than in chimpanzees.
Although not sufficient by itself to cause autism, this reduced baseline expression means that losing a single copy of the gene could push humans below a critical threshold, leading to ASD traits. In other primates, however, even losing one copy would not be sufficient to lower expression enough to cause autism.
These findings could explain why autism, which affects about 1 in 36 U.S. children today, is far more common in humans than in other primates.
“We propose that the down-regulation of ASD-linked genes in humans increased the likelihood of ASD in the human lineage, such that small perturbations during development are sufficient to cause ASD characteristics in humans but not chimpanzees,” researchers explain.
The findings lend weight to a provocative idea, that autism may be, at least in part, a byproduct of the same evolutionary processes that gave rise to modern human intelligence.
Natural selection may have favored genetic configurations that promoted advanced cognition, language, and social behaviors, even if they carried with them an increased vulnerability to neurodevelopmental conditions.
This perspective reframes autism not merely as a disorder but as a potential evolutionary trade-off. While some autism-associated traits can pose challenges, others, such as heightened pattern recognition, attention to detail, and systematizing skills, may have historically provided advantages.
The study does not fully resolve why natural selection would have driven down the expression of autism-linked genes. However, researchers suggest two possibilities.
First, down-regulation of these genes may have slowed postnatal brain development, a hallmark of human evolution compared to other primates. This prolonged developmental window may have enabled greater brain plasticity and learning capacity, particularly in language acquisition.
Second, the changes may have served as a compensatory mechanism. As human brains expanded in size and complexity, they may have risked an imbalance between excitatory and inhibitory neural signaling. Down-regulating specific genes may have helped stabilize these networks, even if it came with the unintended side effect of increasing susceptibility to autism.
Beyond autism, the research provides one of the clearest examples to date of how natural selection for uniquely human traits may have inadvertently raised the risk of neurological and psychiatric conditions. Similar mechanisms may also apply to schizophrenia, which shows overlapping genetic patterns and is likewise more prevalent in humans.
The study underscores a broader principle that evolution is not a perfect engineer. Instead, it is a process of trade-offs, where genetic changes that benefit survival and reproduction may simultaneously introduce vulnerabilities.
Significantly, with a topic as fraught and controversial as autism research, these new findings are not meant to dismiss concerns about external risk factors such as maternal health, environmental exposures, or even the use of medications during pregnancy. Instead, the study provides an evolutionary backdrop that helps explain why humans may be uniquely vulnerable to such influences.
By showing that our brains carry a baseline sensitivity due to profound evolutionary shifts in gene expression, the research suggests that while outside factors can play a role in autism risk, they do so against a genetic landscape already predisposed to long-term cognitive and developmental disorders.
While the findings shed new light on the evolutionary roots of autism, the authors stress the need for further research. The study, which relies on cross-species comparisons and relatively small sample sizes of non-human primates, leaves room for more investigation. Future research using larger cohorts and more detailed developmental models is crucial to fully understand how these evolutionary changes shaped the human brain and could potentially lead to more effective treatments for autism.
“Overall, our analysis suggests that natural selection on gene expression may have increased the prevalence of ASD, and perhaps also SCZ [schizophrenia], in humans,” researchers conclude. “It will be important to develop a deeper understanding of how cell types and genes implicated in ASD and SCZ have evolved in the human lineage, as this will improve our understanding of uniquely human traits and neuropsychiatric disorders.”
Tim McMillan is a retired law enforcement executive, investigative reporter and co-founder of The Debrief. His writing typically focuses on defense, national security, the Intelligence Community and topics related to psychology. You can follow Tim on Twitter: @LtTimMcMillan. Tim can be reached by email: tim@thedebrief.org or through encrypted email: LtTimMcMillan@protonmail.com
