Learn more about Autism Spectrum Disorders.
Introduction by Robert C Bransfield, MD, DLFAPA
Understanding the cause of autism is not a simple process. Autistic patients have a large range of symptoms that are considered to be on a spectrum and these conditions are called Autism Spectrum Disorders (ASD). There are multiple genetic and environmental contributors, multiple processes causing disease and a wide range of symptoms occurring in different individuals. The disease processes are mostly associated with abnormal functioning of the immune system. Normally the immune system responds to threat first with inflammation which ends and is then replaced by antibody production (adaptive immunity). With ASD there are abnormalities in the functioning of the immune system. Inflammation instead may persist and antibodies may be formed that harm the developing nervous system (autoimmunity). The persistence of inflammation is stressful to cells by causing a process called oxidative stress, there can be abnormalities of the energy source within the cell, the mitochondria, and other associated biochemical abnormalities may also occur. Environmental contributors provoking these immune abnormalities include environmental toxic exposures and infectious diseases.
The same infectious and immune process can have a very different effects at different ages—embryonic development, a developing fetus at different developmental stages, the neonate, an infant, a child, an adolescent, an adult and in late life.
A complex approach
Other variables relevant to ASD include which of the 24 infections and coinfections associated with ASD are contributory (Bransfield 2009); whether the infection was previously present or persistent, whether the infection is just in the mother, in the mother and fetus or just in the infant; whether or not there is infection within the central nervous system; whether there were direct effects of the infection vs. immune effects provoked by the infection or both; whether the disease process is caused by inflammation or autoimmunity or both; the presence of toxins; the presence of deficiencies; treatments and response to treatment. Understanding the association between Lyme/tick-borne diseases (LY/TBD) and ASD requires an approach from multiple perspectives. One approach is to compare the similarities between ASD and LY/TBD.
The 15 states most prevalent for autism show a correlation with the 15 states most prevalent for Lyme disease (DeNunzio). Of the twenty states that reported the highest occurrence of Autistic Disorder per 10,000 people; fifteen reported a higher than average number of Lyme disease cases. Conversely, of the twenty states that reported the lowest incidence of Autistic Disorder per 10,000 people; zero reported a higher than average number of Lyme disease cases. (Kuhn et al. 2012). Autism prevalence in California, Oregon and Washington counties is positively associated with precipitation (Waldman M et al. 2008) and precipitation has a positive correlation with tick survival (Nieto NC et al. 2010) which impacts the prevalence of tick-borne diseases.
Evaluating Lyme Disease/Tick-Borne Disease Patients for Autism Spectrum Disorders
Although clinicians have previously noted the association between Lyme disease and ASD (Bransfield et al. 1998) the first study was a comprehensive case history review on the charts of 102 gestational LYD/TBD cases which revealed 9% had been diagnosed with autism and most were diagnosed with a broad spectrum of developmental disabilities. As a control, 66 mothers with Lyme disease who were treated with antibiotics prior to conception and during the entire pregnancy; all gave birth to normal healthy infants (Jones et al. 2005).
Testing Autism Spectrum Disorder Patients for Lyme Disease/Tick-Borne Disease
Most studies demonstrate about 25% of ASD are infected with Borrelia burgdorferi (Vojdani 22%, Lyme Induced Autism Foundation 26%, Nicholson 20-30%, Levin 100% in a Lyme epidemic area of Connecticut), however other infections are also present and may be more prevalent than Borrelia burgdorferi and include Mycoplasma species 56%, with 70% of these especially M. fermentans, Human Herpes Virus-6 (HHV-6) 29%, C. pneumoniae 8%, and also coinfections with Bartonella, Ehrlichia, and Babesia (Nicholson 2007).
Biochemical Similarities between Lyme Disease/Tick-Borne Disease and Autism Spectrum Disorders
LYD/TBD and ASD have biochemical similarities in regard to how the body utilizes oxygen and sulfur. More technically, both have alterations of the oxidoreductive system and homocysteine/methionine metabolism. Both have increases of superoxide dismutase, malondialdehyde and glutathione peroxidase activity. Both have decreased glutathione (Bransfield et al. 2008).
Brain Imaging Similarities between Lyme Disease/Tick-Borne Disease and Autism Spectrum Disorders
LYD/TBD and ASD both include a predominance of white matter findings and significant temporal lobe dysfunction. In ASD the temporal lobe, hippocampal, and amygdala impairments are associated with memory impairments and nonverbal social impairments. Both LYD/TBD and ASD patients demonstrate an excessive sensitivity to light, sound and other stimulation. This clinical observation is supported by brain imaging of patients with LYD/TBD that demonstrates increased thalamus activity (a brain region that gates sensory input) and associated increased activity in auditory and visual areas of cortex (Bransfield et al. 2008).
Immune Similarities between Lyme Disease/Tick-Borne Disease and Autism Spectrum Disorders
LYD/TBD and ASD both have been associated with a combination of inflammatory and autoimmune processes. Both are associated with a persistent inflammation with an elevation of the same components of the immune system (Tumor Necrosis Factor Alpha and Interleukin-6). With both this persistent inflammation is also associated with activation of immune cells within the central nervous system (microglia) and antibodies against brain tissue. Both LYD/TBD and ASD patients are more likely to have the same genetic risk factor, the HLA-DR4 genotype (Bransfield et al. 2008).
Treatment with Antibiotics
Treatment of LYD/TBD during pregnancy can prevent the development of autism and other developmental disabilities associated with LYD/TBD (Jones et al. 2005). Another study has objectively demonstrated that antibiotic treatment can reduce ASD symptoms associated with LYD/TBD (Kuhn et al. 2012).
Economic Cost of Autism Spectrum Disorders Associated with Lyme and Tick-Borne Diseases
Since about 25% of ASD is associated with Borrelia burgdorferi and since well over 50% of ASD is associated with other persistent infections (Nicholson G. 2007) and 673,000 US children have ASD (11 per 1000) with an estimated life-time healthcare cost of $16 million for each person with autism (Kogan MD, 2009), LYD/TBD and other persistent infections appear to be associated with many trillions of dollars in societal costs plus the massive human cost that cannot be converted to dollars.
ASD results from multiple causes with both genetic and environmental contributors, including LYD/TBD. Acute infections in the mother, fetus and/or newborn may cause acute immune reactions and chronic infections in the mother, fetus and/or newborn may cause persistent immune reactions and these immune reactions may adversely affect fetal brain development causing autism spectrum disorder. The recognition that LYD/TBD can be a contributor in a significant number of ASD cases has a significant impact upon prevention and treatment options which can help save life, quality of life and economic viability. When LYD/TBD is present, the antimicrobial treatment of women intending to become pregnant, pregnant women, newborns and autistic spectrum disorder patients can prevent and treat some cases of ASD. ASD associated with LYD/TBD warrants significant attention, research, diagnostic and treatment awareness and advocacy efforts.
Future Directions in Research
Clinically relevant research is needed to better understand this very complex issue. It is necessary to acquire better epidemiological statistics; to better understand the disease contributors (infectious and otherwise) and the interaction of disease contributors, disease deterrents, the multiple pathophysiological processes, the pathophysiology associated with different symptoms and treatment options and effectiveness.
Two articles about the diagnosis of lyme borreliosis in Autism
- Divergent Opinions of Proper Lyme Disease Diagnosis in ASD:
This paper proposes that some children with an autism spectrum disorder (ASD) in the United States have undiagnosed Lyme disease and different testing criteria used by commercial laboratories may be producing false negative results.
- Serologic Markers of Lyme Disease in Children with Autism:
A proposed link between Lyme disease and autism has garnered considerable attention. Among individuals with autism spectrum disorders, rates of seropositivity for Lyme disease of greater than 20% have been reported.