A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology

Abstract

Molecular autism research is evolving toward a biopsychosocial framework that is more informed by autistic experiences. In this context, research aims are moving away from correcting external autistic behaviors and toward alleviating internal distress. Autism Spectrum Conditions (ASCs) are associated with high rates of depression, suicidality and other comorbid psychopathologies, but this relationship is poorly understood. Here, we integrate emerging characterizations of internal autistic experiences within a molecular framework to yield insight into the prevalence of psychopathology in ASC. We demonstrate that descriptions of social camouflaging and autistic burnout resonate closely with the accepted definitions for early life stress (ELS) and chronic adolescent stress (CAS). We propose that social camouflaging could be considered a distinct form of CAS that contributes to allostatic overload, culminating in a pathophysiological state that is experienced as autistic burnout. Autistic burnout is thought to contribute to psychopathology via psychological and physiological mechanisms, but these remain largely unexplored by molecular researchers. Building on converging fields in molecular neuroscience, we discuss the substantial evidence implicating mitochondrial dysfunction in ASC to propose a novel role for mitochondrial allostatic load in the relationship between autism and psychopathology. An interplay between mitochondrial, neuroimmune and neuroendocrine signaling is increasingly implicated in stress-related psychopathologies, and these molecular players are also associated with neurodevelopmental, neurophysiological and neurochemical aspects of ASC. Together, this suggests an increased exposure and underlying molecular susceptibility to ELS that increases the risk of psychopathology in ASC. This article describes an integrative framework shaped by autistic experiences that highlights novel avenues for molecular research into mechanisms that directly affect the quality of life and wellbeing of autistic individuals. Moreover, this framework emphasizes the need for increased access to diagnoses, accommodations, and resources to improve mental health outcomes in autism.

Burnout through the Lenses of Equity/Equality, Diversity and Inclusion and Disabled People: A Scoping Review

“…For example, emotional labour is often linked to burnout [300][301][302][303], and in our relevant abstracts, the emotional labour of trying to fit in was the main factor of burnout mentioned [247,248,250,251,253]. In our study, the factor of emotional labour was mentioned in relation to "autistic burnout".…”

“…None covered concepts such as microaggression, "minority stress", or mentioned theories. Eight covered "autistic burnout" [246][247][248][249][250][251][252][253], five covered autistic people without using the phrase "autistic burnout" [254][255][256][257], and seventeen used the generic term "disability" or terms for specific disabilities such as "learning disability", "cerebral palsy", "cystic fibrosis", "dyslexia", "spinal cord injury", "lumbar disc herniation", "lower back pain", "workers with visual impairment" "deaf and hard of hearing people", and "athletes with a disability" [258][259][260][261][262][263][264][265][266][267][268][269][270][271][272][273][274][275].…”

“…Within the eight abstracts mentioning "autistic burnout" [246][247][248][249][250][251][252][253], three gave definitions [246,248,251]; for example, in one abstract two definitions are given: namely "autistic burnout is described as a debilitating condition that severely impacts functioning, is linked to suicidal ideation and is driven by the stress of masking and living in an unaccommodating neurotypical world", and the second one being "highly debilitating condition characterised by exhaustion, withdrawal, executive function problems and gen-erally reduced functioning, with increased manifestation of autistic traits-and distinct from depression and non-autistic burnout" [246] (p. 2356).…”

“…Five abstracts outlined factors leading to autistic burnout, with a common focus on masking, social camouflaging (behaving as someone one is not), and the need to accommodate "normal" people [247,248,250,251,253]. Stress in one's daily life [253] and lack of autism awareness and acceptance within society [248] were other factors discussed.…”

“…In contrast, those that selected "Has no self-reported disability" reported unfair treatment or discrimination in 15.4% of cases and harassment in 26.0% of cases [129]. At the same time, the need to mask is seen to add to "autistic burnout" [247,248,250,251,253]. Masking is also a problem for other disabled people and can lead to disability/disablism burnout for other groups of disabled people that can, and feel they ought to, mask their "disability".…”