This study highlights the importance of better understanding the interaction between ASD and PTSD, especially because moderate stressful events, considered non-extreme according to diagnostic criteria such as the DSM-5, may be enough to trigger traumatic memories in people with autism.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition resulting from a combination of genetic and environmental factors.
This condition compromises the functioning of neuronal circuits and causes behavioral challenges, such as difficulties in social interaction, repetitive behaviors, and, in many cases, cognitive deficits.
Among the cognitive problems observed are hyper-reactivity to sensory stimuli, memory difficulties, and altered emotional processing, which may predispose individuals with ASD to developing Post-Traumatic Stress Disorder (PTSD) in response to stressful situations.
Both ASD and PTSD share characteristics such as difficulty regulating emotions, rigidity in thinking,g and fragmented autobiographical memory.
However, the relationship between these two disorders is still poorly understood, which limits our understanding of how traumatic stress affects people with autism and what unique mechanisms influence how they perceive traumatic events.
A key player in fear-related memory processing is the medial prefrontal cortex (mPFC), a brain region that regulates executive functions and connects to structures such as the hippocampus and amygdala. Studies indicate that this region is frequently dysfunctional in both ASD and PTSD, highlighting its central role in the interaction between the two disorders.
The mPFC houses specific types of neurons known as parvalbumin interneurons (PV-INs), which control the balance between excitation and inhibition in the brain, essential for sensory processing and adaptation to stressful situations.
These interneurons are particularly relevant to the deficits observed in ASD, as abnormalities in their functioning are linked to the irregular brain activity and social difficulties characteristic of this condition.
Parvalbumin interneurons are critical for maintaining high-frequency firing and autoinhibitory neurotransmission. Source: Sara Hijazi, María P. Pascual García, Yara Nabawi, Steven A. Kushner
Studies in animal models have shown that activating these cells can improve some aspects of social behavior in ASD, suggesting that they may be a promising therapeutic target.
Researchers at the Australian National University explored the interplay between ASD and PTSD by examining how stress affects brain function and memory formation in contactin-associated protein 2 knockouts (Cntnap2 KO) mice, which recapitulate key symptoms of ASD.
They found that exposure to moderate levels of stress can lead to the development of PTSD-like traumatic memories in these animals, in addition to worsening behavioral traits associated with autism.
This was attributed to hyperactivation of the mPFC and dysregulation of parvalbumin interneuron function.
mPFC and PV-INs in PTSD-like memory formation. (A) Density of c-FOS positive cells between control (black) and autistic (magenta) groups. c-Fos is a protein expressed in cells when they are actively involved in neuronal signaling. Here, we measure the increase in c-Fos expression after recall of a context, indicating neuronal activation in response to the stimulus. (B) The images show areas of the brain where c-Fos is expressed. Red areas indicate regions where neurons were activated in response to recall of the context. Single arrowheads: Indicate cells labeled by both c-Fos and PV (parvalbumin neurons). Empty arrowheads: Indicate cells that are positive for c-Fos but do not express PV. This distinction helps to identify which types of neurons are involved in the response. (C) The proportion of c-FOS positive cells in the population of PV-INs (parvalbumin interneurons). A specific subtype of neurons that plays a key role in controlling brain activity and the excitation/inhibition balance.
In addition, the study showed that these traumatic memories can be partially reversed by recontextualization techniques, which reduce the negative effects of stress on core symptoms of ASD.
These findings suggest that the impact of PTSD on autism may be more profound than previously thought, influencing the severity of core traits of the disorder.
The results highlight the importance of better understanding the interaction between ASD and PTSD, especially since moderate stressful events, considered non-extreme according to diagnostic criteria such as the DSM-5, may be enough to trigger traumatic memories in people with autism.
This vulnerability highlights the need for specific therapeutic interventions to deal with stress in individuals with ASD, to mitigate the risk of developing PTSD, and to improve their quality of life.
READ MORE:
Parvalbumin interneuron activity in autism underlies susceptibility to PTSD-like memory formation
Alice Shaam Al-Abed, Tiarne Vickie Allen, Noorya Yasmin Ahmed, Azza Sellami, Yovina Sontani, Elise Caitlin Rawlinson, Aline Marighetto, Aline Desmedt and Nathalie Dehorter
iScience, Volume 27, Issue 5, 109747
DOI: 10.1016/j.isci.2024.109747
Abstract:
A rising concern in autism spectrum disorder (ASD) is the heightened sensitivity to trauma, the potential consequences of which have been overlooked, particularly upon the severity of the ASD traits. We first demonstrate a reciprocal relationship between ASD and post-traumatic stress disorder (PTSD) and reveal that exposure to a mildly stressful event induces PTSD-like memory in four mouse models of ASD. We also establish an unanticipated consequence of stress, as the formation of PTSD-like memory leads to the aggravation of core autistic traits. Such susceptibility to developing PTSD-like memory in ASD stems from hyperactivation of the prefrontal cortex and altered fine-tuning of parvalbumin interneuron firing. A traumatic memory can be treated by recontextualization, reducing the deleterious effects on the core symptoms of ASD in the Cntnap2 KO mouse model. This study provides a neurobiological and psychological framework for future examination of the impact of PTSD-like memory in autism.
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