Selective modulation of the glucocorticoid receptor with CORT108297 during chronic adolescent stress evokes sex-specific effects in adulthood

Cotella, Evelin M.; Morano, Rachel; Wulsin, Aynara C.; Martelle, Susan E.; Lemen, Paige; Fitzgerald, Malinda E.C.; Ba, Packard; Moloney, Rachel D.; Herman, James P.

doi:10.1101/646745

Cited by 1 publication

(1 citation statement)

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“…Furthermore, disruptions to cortisol and catecholamine signaling have been reported in individuals with a history of ELS who develop PTSD, depression and suicidality (164). Recent work in animal models has also shown distinct perturbations to HPA axis signaling, stress reactivity, and cognitive and emotional functioning in response to both ELS and CAS (165).…”

Section: Mal and The Hpa Axis In Stress-related Psychopathologymentioning

confidence: 99%

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

Mahony

O’Ryan

2022

Front. Psychiatry

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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.

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Section: Mal and The Hpa Axis In Stress-related Psychopathologymentioning

confidence: 99%