Dr. Robert Naviaux, a professor of medicine, pediatrics and pathology at UC San Diego School of Medicine, suggests that a built-in stress response, called the cell danger response (CDR), might explain autism:
The review pulls together more than ten years of research across genetics, metabolism, toxicology and early brain development.
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The first hit is genetic predisposition: some children inherit a “sensitive genotype” that makes their mitochondria and cellular signaling systems highly reactive to environmental changes. These can range from specific genetic syndromes to a combination of common variants. On their own, these genetic traits do not cause autism, but they create biological hypersensitivity to stress.
The second hit occurs when the environment triggers this sensitivity. This happens during a critical window from early pregnancy through the first 18–36 months of life. Triggers can include maternal immune activation, pollution or metabolic stressors. In this model, early triggers push sensitive cells into a stress state at the wrong moment.
The third hit is when that stress state continues for months during late pregnancy or early childhood. Long periods of cellular stress are proposed to disturb normal brain development, reshape mitochondria and influence gut microbes and the immune system.
Across these three hits, one mechanism ties the model together: a signaling molecule called extracellular ATP (eATP), a molecule that acts as a “danger signal”. When eATP levels stay high, cells remain in a defensive mode rather than returning to normal growth. Naviaux argues that this is not a malfunction, but rather mitochondria responding exactly as designed to a perceived threat.
“Behavior has a chemical basis. The CDR regulates that chemistry,” Naviaux explained. “When it remains activated too long, it diverts the body’s resources from normal growth and development toward cellular defense, leaving fewer resources for the developing brain.”
The review explains that the CDR is part of a universal healing cycle called salugenesis; in autism, this cycle gets stuck, preventing the return to normal cellular function. This prolonged stress prevents the necessary developmental shift from excitatory to inhibitory signaling in the brain, leading to over-excitation.
This framework also explains why many autistic children experience physical symptoms such as gut issues or sleep disturbances – signs of a body-wide stress response.