Abstract
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.
Highlights
What Is Autism?Autism spectrum disorders (ASD) are a group of complex and heterogenous neurodevelopmental conditions, with lifelong presentations in behavior, communication, cognition, and mental health
This paper argues that the pro-inflammatory state of children with ASD arises from chronic Sympathetic nervous system (SNS)-HPA hyperarousal, or stress and anxiety, with longterm multi-directional impacts upon gut health, behavior and immune trajectories (De Palma et al, 2014; Gottfried et al, 2015; Siniscalco, 2015; Ding et al, 2017; Carter, 2019)
This paper proposes that chronic anxiety and gastrointestinal problems in children and adults diagnosed with ASD are a downstream effect of chronic Sympathetic nervous system and hypothalamic-pituitary-adrenal axis (SNS-HPA) axis dysregulation that begins in very early life
Summary
Autism spectrum disorders (ASD) are a group of complex and heterogenous neurodevelopmental conditions, with lifelong presentations in behavior, communication, cognition, and mental health. Variable phenotypic expressions emerge out of the compensations of the child’s neural networks in response to very early lesions, as myriad feedback loops in the complex adaptive system of the global neuronal workspace compensate for deficiencies and maintain the best possible functional stability This may occur at the expense of, or with unusual development of and compensation by, higher order cognitive functions like memory, attention and executive functions. Genetic studies continue to search for risk variants of small effect in complex groups, biological research proceeds in its attempt to find unitary underlying commonalities in members of the ASD category, and early detection research continues to search in vain for markers with clinically useful specificities and sensitivities In this context, Dawson calls for “new and paradigm-shifting interventions and research methodologies which embrace heterogeneity,” and Charman highlights the need to “[transfer] new knowledge about risk factors, biomarkers, and behavioral signs into practical applications” for health professionals (Amaral et al, 2019). THE FIRST 100 DAYS POST-TERM: WINDOW OF CRITICALLY INJURY-SENSITIVE NEUROPLASTICITY
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