Autism Emergence Timeline: Oxidative Burden and Buffering Capacity Influence the Timing of Late Diagnosis and Regression

Autism spectrum disorder (ASD) research has treated early regression, late regression, late diagnosis without documented childhood symptoms, and the sex disparity in diagnostic timing as separate phenomena. We propose that early regression, late regression, and genuinely late-emerging late diagnoses may share one process in some cases: cumulative oxidative and inflammatory burden from environmental chemical exposure, infection and autoimmune activity (including PANS/PANDAS, maternal immune activation, and folate receptor alpha autoantibody-mediated cerebral folate deficiency), and chronic psychosocial stress including adverse childhood experiences, mediated in part by gut-microbiome-dependent folate and B12 status. ASD liability is largely genetic; the burden is proposed to act on the timing and severity of presentation, not as an alternative. Individual, including sex-linked, buffering capacity determines whether and when the burden crosses a functional threshold. Developmental timing of any such crossing, rather than the specific exposure, determines presentation: no phenotype, early-onset ASD, early or late regression, or, in genuinely late-emerging cases, gradual late diagnosis. Belated recognition of early-present traits is outside the model. A speculative buffering hypothesis complements, and does not replace, the dominant masking account of the sex disparity. This is a theoretical synthesis rather than an established causal model: no study yet measures these factors together, and we outline the prospective evidence needed to test it. The model does not, at present, support any specific treatment for ASD or regression.