Preprint Concept Paper Version 1 Preserved in Portico This version is not peer-reviewed

A Molecular Framework for Autistic Experiences: Mitochondrial Allostatic Load as A Mediator between Autism and Psychopathology

Version 1 : Received: 18 May 2022 / Approved: 21 May 2022 / Online: 21 May 2022 (10:53:46 CEST)
Version 2 : Received: 3 September 2022 / Approved: 5 September 2022 / Online: 5 September 2022 (03:35:24 CEST)

A peer-reviewed article of this Preprint also exists.

Mahony C and O’Ryan C (2022) A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology. Front. Psychiatry 13:985713. doi: 10.3389/fpsyt.2022.985713 Mahony C and O’Ryan C (2022) A molecular framework for autistic experiences: Mitochondrial allostatic load as a mediator between autism and psychopathology. Front. Psychiatry 13:985713. doi: 10.3389/fpsyt.2022.985713

Abstract

Molecular research into Autism Spectrum Conditions (ASC) is undergoing an essential shift towards a biopsychosocial framework that is informed by autistic experiences. In this context, research aims are moving away from correcting external autistic behaviors and towards alleviating internal distress. ASC is associated with high rates of depression, suicidality and comorbid psychopathologies, but the underlying mechanisms that mediate this relationship are poorly understood. Here, we integrate emerging psychosocial characterizations of internal autistic experiences within a molecular framework to yield insight into the prevalence of psychopathology in ASC. We demonstrate that recent conceptualizations 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 ELS that contributes to allostatic load, culminating in a pathophysiological state that is experienced as autistic burnout. Autistic burnout is thought to contribute to psychopathology via both psychosocial and neurophysiological mechanisms, but these remain largely unexplored by molecular researchers. Considering recent insights from converging bodies of work 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 metabolism, 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 etiology. Together, this suggests an increased exposure to, and an 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 future research into molecular mechanisms that affect the quality of life and well-being of autistic individuals. Moreover, this framework emphasizes the need for increased access to diagnosis, accommodations, and resources to improve mental health outcomes in autism.

Keywords

autism; autistic burnout; social camouflaging; early life stress; suicidality; psychopathology; mitochondrial allostatic load

Subject

Medicine and Pharmacology, Neuroscience and Neurology

Comments (0)

Comment 1
Received: 18 July 2022
Commenter: Kristen Deloughery
The commenter has declared there is no conflict of interests.
Comment: I just wanted to say thank you for writing this paper. I cannot tell you how exciting and hopeful it is to read an article with this kind of approach to molecular ASC research.
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