Pre-emptive Intervention for Autism Spectrum Disorder: Theoretical Foundations and Clinical Translation.

Autism spectrum disorders (ASD) are an emergent public health problem, placing significant burden upon the individual, family and health system. ASD are polygenetic spectrum disorders of neural connectome development, in which one or more feedback loops amplify small genetic, structural, or functional variations in the very early development of motor and sensory-motor pathways. These perturbations trigger a 'butterfly effect' of unpredictable cascades of structural and functional imbalances in the global neuronal workspace, resulting in atypical behaviors, social communication, and cognition long-term. The first 100 days post-term are critically neuroplastic and comprise an injury-sensitive developmental window, characterized by a neural biomarker, the persistence of the cortical subplate, and a behavioral biomarker, the crying diathesis. By the time potential diagnostic signs are identified, from 6 months of age, ASD neuropathy is already entrenched. The International Society for Autism Research Special Interest Group has called for pre-emptive intervention, based upon rigorous theoretical frames, and real world translation and evaluation. This paper responds to that call. It synthesizes heterogenous evidence concerning ASD etiologies from both psychosocial and biological research literatures with complexity science and evolutionary biology, to propose a theoretical framework for pre-emptive intervention. This paper hypothesizes that environmental factors resulting from a mismatch between environment of evolutionary adaptedness and culture initiate or perpetuate early motor and sensory-motor lesions, triggering a butterfly effect of multi-directional cascades of atypical developmental in the complex adaptive system of the parent and ASD-susceptible infant. Chronic sympathetic nervous system/hypothalamic-pituitary-adrenal axis hyperarousal and disrupted parent-infant biobehavioral synchrony are the key biologic and behavioral mechanisms perpetuating these atypical developmental cascades. A clinical translation of this evidence is proposed, for application antenatally and in the first 6 months of life, as pre-emptive intervention for ASD.