Research and Publications
Autism research is multifaceted and ongoing. Areas of current exploration are organized by topic with links to scientific articles, presentations, and other resources.
This is a curated list of some of my research and publications organized by topics of interest.
Click to expand each topic.
Folate Metabolism in Autism Spectrum Disorder
Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). They disrupt the transportation of folate across the blood-brain barrier by binding to the FRα. Children with ASD and FRAAs have been reported to respond well to treatment with a form of folate known as folinic acid, suggesting that they may be an important ASD subgroup to identify and treat.
Environmental Factors in Autism
Genetic abnormalities in autism spectrum disorders (ASD) are widely-accepted; however, recent studies point to an equal contribution by environmental factors, particularly environmental toxicants. New publications investigating potential associations between environmental toxicants and ASD examine the estimated toxicant exposures in the environment during the preconceptional, gestational and early childhood periods; look for biomarkers of toxicants; and examine potential genetic susceptibilities to toxicants.
Seizures and Epilepsy in Autism Spectrum Disorder
Seizures are very common in individuals with autism as are abnormal electroencephalogram recordings with seizure-like activity. Additionally a diagnosis of epilepsy is found in up to 40% of children with autism and, in many cases, is refractory to treatment. The pathology that causes epilepsy also has been implemented in children with autism.
Immune Dysfunction in Autism
Recent studies suggest that ASD is associated with immune system dysfunction. In individuals with ASD, inflammatory cytokines are often elevated in the blood and brain. Children with ASD sometimes have autoantibodies to brain tissue as well as to non-brain tissue such as the folate receptor alpha (FRα) and mitochondria. Another recent area of interest is in the overlap between ASD and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infection (PANDAS) and Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS).
Redox Metabolism Abnormalities in Autism
Autism is associated with an imbalance in glutathione-dependent redox metabolism. Glutathione synthesis and intracellular redox balance are linked to folate and methylation metabolism, metabolic pathways that have also been shown to be abnormal in ASD. Together, these metabolic abnormalities define a distinct ASD endophenotype that is closely associated with genetic, epigenetic and mitochondrial abnormalities, as well as environmental factors related to ASD. Biomarkers that reflect these metabolic abnormalities have recently been investigated to find ASD metabolic endophenotype that may lead to a better understanding of the pathophysiological mechanisms underlying core and associated ASD symptoms and may lead to new treatments.
The Role of the Microbiome in Autism
Increasing evidence suggests that the enteric microbiome plays a critical role in the etiology and symptomatology of ASD, at least in some cases. To better understand this connection, the International Symposium on the Microbiome in Health and Disease has been organized to focus on novel approaches for studying and manipulating the enteric microbiome to improve autism symptoms. From this meeting a special issue of Microbial Ecology in Health and Disease was published. We have also investigated the clinical and basic research aspects of enteric microbiome metabolites on mitochondrial function.
Mitochondrial Function in Autism Spectrum Disorder
Abnormalities in mitochondrial function appear to affect a significant number of children with autism spectrum disorder (ASD) but the nature of these abnormalities is poorly understood. Through critical literature reviews, clinical research and basic research, my team and I have investigated the nature of mitochondrial abnormalities in ASD. Our recent research suggests the nature of mitochondrial dysfunction in ASD is distinct from other forms of mitochondrial disease in its metabolic nature and with respect to molecular signaling pathways. We have developed a model of mitochondrial dysfunction related to ASD based on cell lines to allow us to study it in the laboratory in detail.
mRNA in Autism Spectrum Disorder
Mutations in hundreds of different genes contribute to to the risk of Autism spectrum disorder (ASD). Studies have shown that significant differences in the ASD-associated miRNA expression profiles are found in a variety of target tissues (e.g., saliva, blood, serum and brain). In some studies, significant dysregulation of specific miRNAs has been found in lymphoblastoid cell lines (LCLs) of ASD patients compared to their typically-developing siblings and controls. Overall, these findings suggest that mRNA and miRNA expression profiles in ASD reveal numerous miRNA–gene interactions that regulate critical pathways involved in the proliferation of neuronal cells, cell death of immune cells, and neuronal development. This is a promising area for future discoveries and possible treatments.
Neuroimaging in Autism Spectrum Disorder
Neuroimaging has uncovered connectivity abnormalities in the brains of individuals with autism spectrum disorders (ASD). The precise connectivity abnormalities and the relationship between these abnormalities and cognition/ASD symptoms is unknown. Functional magnetic resonance imaging and other advances in neuroimaging may have clinical utility as non-invasive ways to investigate these neurochemical alterations in ASD. MRI provides dynamic insight into the functional organization of the brains’ activity and measures the function of neurotransmitter-driven networks. New applications of neuroimaging can help us evaluate treatments for patients with ASD and other neurodevelopmental disorders.
Treatments for Autism
Despite the fact that the prevalence of autism spectrum disorder (ASD) continues to rise, no effective medical treatments have become standard of care. As the pathophysiological abnormalities associated with ASD are studied, we hope that these revelations lead to associated treatments. Treatments targeting some of the abnormalities seen in ASD including neurotransmitter abnormalities, particularly imbalances in glutamate and acetylcholine, sleep onset disorder (with behavioral therapy and melatonin), and metabolic abnormalities in folate, cobalamin, tetrahydrobiopterin, carnitine, and redox pathways are being investigated. There is some evidence for treatments of epilepsy and seizures, mitochondrial and immune disorders, and gastrointestinal abnormalities, particularly imbalances in the enteric microbiome, but further clinical studies are needed in these areas to better define treatments specific to children with ASD. There are some promising areas of ASD research that could lead to novel treatments that could become standard of care in the future.