Traditionally, Autism Spectrum Disorders has been framed as a behavioral disorder. ASDs are a heterogenous group of neurodevelopmental disorders are characterized by impairments in communication and social interaction problems and repetitive behaviors.
In the United States, ASD affects 1 out of 51 individuals – with four times more males than females being affected. Fragile X syndrome and Rett syndrome and several genetic syndromes have been associated with ASD.
Although many of the behavioral and cognitive features of ASD are linked from dysfunction of the brain, many fields of medicine has evidences that besides the brain, physiological abnormalities are associated with ASD. This suggests that in some cases, rather than organ specific abnormalities, ASD arises from systemic abnormalities.
Clinical studies and research have shown physiological and metabolic systems that transcend specific organ dysfunction, such as immune dysregulation and inflammation, abnormalities in redox regulation and oxidative stress, and dysfunction of energy generation and mitochondrial systems
In this context, rather than being a purely central nervous system (CNS) disorder, at least in a subset of individuals with ASD, it may arise from, or at least involve, systemic physiological abnormalities. However, because the CNS is affected in ASD, examining physiological abnormalities in the brain may reveal more about what is abnormal than inspecting abnormalities in blood or urine samples.
There are a number of studies that reported evidence of oxidative stress in individuals with ASD. And in some studies, ASD has been correlated with genetic variations in glutathione-related pathways.
Several case-control studies have reported lower concentrations of reduced glutathione (GSH), higher levels of oxidized glutathione (GSSG) and a decrease in the GSH/GSSG redox ratio, along with a lower mitochondrial GSH reserve in individuals with ASD compared to controls.
In addition, ASD severity has been correlated with lower GSH levels and markers of increased oxidative stress. Notably, these aforementioned studies examined peripheral markers of oxidative stress, including those found in blood and urine. Recently, a number of studies have reported evidence of oxidative stress in post-mortem brain samples from individuals with ASD compared to controls
Evidence of mitochondrial dysfunction in individuals with ASD
Recently, several studies have reported evidence of mitochondrial dysfunction in ASD brain samples compared to controls. One systematic review reported that over 30% of children with ASD have biomarkers of abnormal mitochondrial function suggesting that a relatively high percentage of individuals with ASD might have some degree of mitochondrial dysfunction. Another study reported that up to 50% of children with ASD have biomarkers of mitochondrial dysfunction that are valid (that is, they correlate with other biomarkers of mitochondrial dysfunction) and are consistently abnormal (that is, they are repeatedly abnormal). However, like the studies on oxidative stress and ASD, most of the published literature concerning mitochondrial dysfunction has examined blood and urine samples.
Immune Dysregulation and/or inflammation of the brain
Gene changes pertaining to the immune system along with other immune dysregulation and/or inflammation have been reported in
Although there have been many studies examining immune abnormalities in ASD, almost all these studies have examined blood and urine samples. However, some studies have recently reported evidence of brain-related immune dysregulation or inflammation in ASD compared to controls
Recently, an interrelationship between oxidative stress, mitochondrial dysfunction, and/or inflammation has been reported in some individuals with autism. In this blog, we concentrate on studies that have documented these physiological abnormalities specifically in the CNS of individuals with ASD. Reviewing the evidence for these physiological abnormalities specifically in the CNS is important for several reasons.
Firstly, the CNS is protected from the rest of the body by the blood-brain barrier. Although there is evidence that these physiological abnormalities are present in non-CNS tissue in individuals with ASD, it does not necessarily mean that they are present in the CNS.
Demonstrating that these abnormalities also affect the brain would suggest that brain dysfunction in individuals with ASD is not necessarily only secondary to systematic abnormalities, but that the same abnormalities that influence peripheral organs also directly influence brain function. Secondly, there are particular patterns of abnormalities in the CNS that are associated with ASD.
Indeed, abnormalities in ASD have been reported in the frontal and temporal cortices, the hippocampus and amygdala as well as the cerebellum. Determining whether these physiological abnormalities are also present in these brain areas would provide insight into whether they could be involved in the pathological mechanisms that result in ASD.
Thus, this blog reviews the evidence for oxidative stress, mitochondrial dysfunction and immune dysregulation/inflammation in the brains of individuals with ASD compared to controls as well as the evidence linking these abnormalities.
A wide range of neurodegenerative diseases including Alzheimer, Parkinson’s, Multiple Sclerosis, Amyotrophic Lateral Sclerosis and Friedreich’s ataxia have been correlated with mitochondrial dysfunction, oxidative stress, and inflammation. Therefore, future research will need to investigate which pathophysiological mechanisms are shared among these diseases. Such knowledge may lead to novel treatments and strategies for preventing these pathophysiological processes, and thus neurocognitive and psychiatric diseases, from developing.
If you are a mother or a father or a guardian to a child diagnosed with autism and other neurodevelopmental disorders and are interested in the things we have just discussed or maybe you have questions regarding the topic – don’t hesitate to comment below. We are here to help you and we are more than ready to join your lifelong journey. Also, please do not hesitate to consult us at Fresno/Clovis A+ Integrative Brain Restoration Clinic!
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