Figure 1.

Competing models for the causal sub structure of autism. In the traditional model (Panel A), inherited liabilities corresponding to the three characterizing symptom manifestations of autism (the so-called “autism triad”) contribute to genetic susceptibility for autism (See Frazier et al., 2014) In a reconceptualization informed by recent developmental research (Panel B), permutations and combinations of independent inherited liabilities (A through X, none specific to a particular autism symptom domain nor to autism itself) contribute to allostatic load for a singular latent quantitative trait (“autism”) which secondarily gives rise to the array of characterizing traits and features of the autistic syndrome. Notable implications of reconceptualization B include: (i) a unitary factor structure for the manifest symptoms of autism (i.e. that they arise from a singular underlying biological deficit), and (ii) genotype-phenotype associations will be more pronounced for the relationship between each inherited liability (A-X) and a sub structural neurobehavioral trait (a-x) than for genotypic association with “autism”, especially if autism can arise from numerous combinatorial aggregations of a-x, the effects of which might be accentuated by de novo mutations, perinatal complications, or stochastic influences on brain development.