Hyperbaric Oxygen Therapy (HBOT) has traditionally been used to treat many clinical disorders like arterial gas embolism, problem wounds, and decompression sickness. Recently, the therapy has been employed for treating individuals with ASD (Autism Spectrum Disorders). Many individuals with ASD are affected by some physiological abnormalities, which can be ameliorated with HBOT, including oxidative stress, mitochondrial dysfunction, inflammation, and cerebral hypoperfusion.
Studies of kids with ASD have shown that HBOT leads to positive changes in behavior and/or physiology. For example, it has been reported by some studies that Hyperbaric Oxygen Therapy improved cerebral perfusion and reduced inflammation. Additionally, the therapy did not worsen markers of oxidative stress in children with ASD. Most of the studies of HBOT in kids with ASD evaluated behavioral changes and showed improvements in various behavioral domains, though some of such studies weren’t controlled.
In this article, we will discuss the effects of Hyperbaric Oxygen Therapy on various physiological abnormalities associated with ASD. However, before that let’s look at what is HBOT.
What is Hyperbaric Oxygen Therapy (HBOT)?
Hyperbaric Oxygen Therapy (HBOT) is a treatment method involving the inhalation of 100% oxygen, at a pressure higher than 1 atmosphere (atm), inside a pressurized chamber called a hyperbaric chamber. As mentioned earlier, the therapy is used in the treatment of various medical conditions including carbon monoxide poisoning, arterial gas embolism, problem wounds, and decompression sickness. HBOT treatment for these conditions employs greater pressures (more than 2.0 atm). It has been shown that higher pressure Hyperbaric Oxygen Therapy increases the amount of oxygen in body tissues and plasma, and may result in normalization of oxygen level in ischemic tissues.
Effects of HBOT on Physiological Abnormalities in ASD
Following is discussed the effects of Hyperbaric Oxygen Therapy on various physiological abnormalities involved in Autism Spectrum Disorders:
1. Cerebral Hypoperfusion
As reported by many studies, individuals with ASD are affected by cerebral hypoperfusion in comparison to controls, as measured by functional magnetic resonance imaging (fMRI), SPECT, or positron emission tomography (PET). A correlation has been found between this hypoperfusion and certain autistic behaviors like reduced language development, impairment in processing emotions and facial expressions, willingness for sameness, and repetitive behavior. Moreover, a significant correlation has been found between reduced cerebral perfusion and ascending age in kids with ASD and greater autistic behaviors.
HBOT has the potential to improve cerebral perfusion involved in ASD. It has been reported by many studies that HBOT at low pressures (1.3 to 1.5 atm) has led to significant improvement in cerebral perfusion, as measured by post- and pre-HBOT SPECT scans in various neurological issues like chronic brain injury and TBI (Traumatic Brain Injury). Additionally, it has been shown that cerebral perfusion changes in kids with ASD following HBOT treatment. For instance, it has been shown by various case reports that HBOT at 1.3 atm/24% oxygen leads to improvement in cerebral perfusion, based on measurements by post- and pre-treatment SPECT scans. These case reports include one autistic child who received HBOT for 1 hour per day for 10 days consecutively, and two autistic kids who were given 40-80 HBOT treatments. Improvements in behavior were observed in the children.
Recent studies agree upon the conviction that some people with ASD display neuroinflammation, gastrointestinal inflammation, and/or immune dysregulation.
HBOT treatment has been demonstrated to have significant anti-inflammatory properties, both in human and animal studies. According to reports, HBOT decreases the generation of pro-inflammatory cytokines (which include IL-6, IL-1, interferon-gamma, and TNF-alpha) in animal and human studies. The treatment also increases the levels of counter-inflammatory IL-10. In a study, the therapy decreased the levels of neopterin also. Moreover, a systematic review conducted recently reported improvement in studies which employed Hyperbaric Oxygen Therapy in IBD (Inflammatory Bowel Disease). HBOT’s effect on inflammation reduction may be a result of pressure-related effect rather than delivery of oxygen.
3. Mitochondrial Dysfunction
Some people with autism display symptoms of mitochondrial dysfunction. Treatments are relatively limited for mitochondrial dysfunction, however, recently interest has increased in employing HBOT as a treatment. HBOT effects on mitochondrial function has been examined by human as well as animal studies. It has been reported by various animal models that HBOT contributes to mitochondrial function improvement.
In a study involving rats having normal mitochondrial function, ATP production in muscle tissue was increased by HBOT in comparison to a control group. As reported by a study of rat hippocampus, HBOT heightened mitochondrial autophagy and biogenesis with the help of, in part, a raised production of ROS (Reactive Oxygen Species). This process resulted in the production of new healthy mitochondrial and destruction of old dysfunctional mitochondrial. Additionally, this study found increase in activation of mitochondrial DNA replication and transcription with Hyperbaric Oxygen Therapy. However, further research is necessary on HBOT effects on mitochondrial function for people with autism.
4. Oxidative Stress
Various studies have shown evidences of oxidative stress in kids with ASD. Several investigators have shown concern that Hyperbaric Oxygen Therapy may augment oxidative stress in kids with ASD, who have heightened oxidative stress. According to theory, HBOT may enhance oxidative stress due to increased ROS production, from high oxygen concentration. Such a phenomenon may occur since an increased delivery of oxygen to mitochondria may raise ROS generation.
However, it has been shown that HBOT upregulates the generation of antioxidant enzymes like heme-oxygenase 1, paraoxonase, catalase, glutathione peroxidase, and superoxide dismutase. This boost in levels of antioxidant enzymes is referred to as “conditioning” and has the ability to protect from damage caused by Reactive Oxygen Species. Augmenting ROS may be HBOT’s mechanism of action since ROS have a vital role to play in cellular signalling as well as triggering specific metabolic pathways. Moreover, a slight ROS increase generated by HBOT may turn out to be advantageous since these ROS seem to increase mitochondrial biogenesis.
In a study, 12 autistic children were given HBOT at 1.3 atm/24% of oxygen, and 6 kids were given HBOT at 1.5 atm/100% of oxygen. The biomarkers were measured prior to and following 40 sessions of HBOT. Improvements in behavior were noticed in these kids. Furthermore, levels of plasma oxidized glutathione did not change significantly at 1.5 atm (p = 0.583) or 1.3 atm (p = 0.557).
When intracellular level exceeds redox capacity, oxidized glutathione gets exported from cells. Therefore, this finding indicates intracellular oxidative stress had not worsened significantly on HBOT administration at these commonly employed low HBOT pressures in Autism Spectrum Disorders.
Based on the findings of various studies conducted on HBOT effects on ASD, researchers concluded that Hyperbaric Oxygen Therapy is a safe as well as potentially effective treatment option for kids with ASD. However, more studies are needed in this area. In further studies, it would be wise to employ standardized physiological biomarkers and behavioral measurement tools in controlled study design.