Fig. 2.

Schematic illustration of a developmentally sensitive two-hit model of autism. We propose that the first hit (i.e., genetic and neurodevelopmental disruptions) calibrates the system to be fundamentally vulnerable, which leads to poor childhood outcomes. A subsequent second hit (adolescent-specific developmental tasks and pubertal hormones) compounds previous neural vulnerabilities in addition to creating new and importantly different vulnerabilities, which lead to impediments in attaining adult levels of adaptive functioning. Colored lines within the diagram are numbered by area of research. The blue line predicts links between vulnerable neural circuits and poor childhood outcomes, which has been minimally characterized in the literature. The green lines are symbolic of two predictions that have yet to be addressed: how poor childhood outcomes cascade into poor adolescent outcomes and how poor adolescent outcomes (as a result of a second hit) lead to a failure to transition into adult social roles and levels of adaptive functioning.