A Unifying Theory for Autism: The Pathogenetic Triad as a Theoretical Framework

Abstract

This paper presents a unifying theory for autism by applying the framework of a pathogenetic triad to the scientific literature. It proposes a deconstruction of autism into three contributing features (an autistic personality dimension, cognitive compensation, and neuropathological risk factors), and delineates how they interact to cause a maladaptive behavioral phenotype that may require a clinical diagnosis. The autistic personality represents a common core condition, which induces a set of behavioral issues when pronounced. These issues are compensated for by cognitive mechanisms, allowing the individual to remain adaptive and functional. Risk factors, both exogenous and endogenous ones, show pathophysiological convergence through their negative effects on neurodevelopment. This secondarily affects cognitive compensation, which disinhibits a maladaptive behavioral phenotype. The triad is operationalized and methods for quantification are presented. With respect to the breadth of findings in the literature that it can incorporate, it is the most comprehensive model yet for autism. Its main implications are that (1) it presents the broader autism phenotype as a non-pathological core personality domain, which is shared across the population and uncoupled from associated features such as low cognitive ability and immune dysfunction, (2) it proposes that common genetic variants underly the personality domain, and that rare variants act as risk factors through negative effects on neurodevelopment, (3) it outlines a common pathophysiological mechanism, through inhibition of neurodevelopment and cognitive dysfunction, by which a wide range of endogenous and exogenous risk factors lead to autism, and (4) it suggests that contributing risk factors, and findings of immune and autonomic dysfunction are clinically ascertained rather than part of the core autism construct.

Integrating the Autistic Experience Into Existing Models for Disordered Eating

“…Within autism research, the autistic personality (AP) consists of behaviors denoting an underlying neurobiological endophenotype identified within the diagnostic profile for autism (Landry and Chouinard, 2016 ; Sarovic, 2021 ). The AP conceptualizes autism as being manifold (see Sarovic, 2021 ), in contrast to the Autism Quotient Questionnaire (AQ) (Baron-Cohen et al, 2001 ), which originally quantified autistic traits as being unidimensional – that is, the “continuum from ASD to normality” (Murray et al, 2014 , p. 56). This notion of normality has, in effect, led to current research and practice to compare – and inherently pathologize – AP features against behaviors which are traditionally considered ‘typical' (Sucksmith et al, 2011 ).…”

“…While the AP and AQ both recognize phenotypic issues – in particular, presentations of a maladaptive behavioral phenotype (Sarovic, 2021 ) – the AP is more complex by accounting for the accumulative effect of behavioral difficulties (e.g., altered sensory processing) subsequent to cognitive compensation (CC): the cognitive ability to compensate for, and overcome, maladaptive AP features through learning and carrying out adaptive responses (see Pugliese et al, 2015 , 2016 ; Livingston and Happé, 2017 ). Although relatively temporally stable, CC is dependent on internal (e.g., heritability, executive function) and external factors (e.g., day-to-day cognitive demands; Happé and Frith, 2006 ; Livingston and Happé, 2017 ).…”

“…Moreover, impaired CC increases the probability of the AP to become both pronounced and maladaptive, giving rise to complex mental health difficulties (Geurts et al, 2014 ; Ullman and Pullman, 2015 ; Lever and Geurts, 2016 ). Overall, rather than applying a diagnosis of AN across all samples presenting restrictive eating and/or body dissatisfaction, we argue additional investigation to determine whether such symptomatology is simply features of the AP (e.g., lower interoceptive awareness) or inadequate CC/maladaptive AP (Sarovic, 2021 ).…”

Orexin/Hypocretin System Dysfunction in ESSENCE (Early Symptomatic Syndromes Eliciting Neurodevelopmental Clinical Examinations)

“…HRV as indicator of “flexible and adaptive autonomic response systems”, has become a crucial part of the pathogenetic triad in proposed unifying theory for ASD 189 …”

“…• Different HRV measures may give significant insights into sustained attention, as well as in the impairments of behavioral and emotional regulation in ADHD 188 • HRV as indicator of "flexible and adaptive autonomic response systems", has become a crucial part of the pathogenetic triad in proposed unifying theory for ASD 189 • HRV during periods of non-stress was associated with greater stress resilience 190 • HRV belongs to the RDoC arousal domain 8…”