New and Emerging Research Findings in Autism Spectrum Disorders

  • Recent Studies Reveal Some of the Factors Related to Autism and Offer New Treatment Possibilities

    Suruchi Chandra, MD

    Autism spectrum disorders (ASD) have traditionally been thought of as genetic disorders that result in changes to the structure or hard wiring of the brain. This conceptualization or understanding of autism offered little hope for preventing or treating autism. At best, autism could be managed with behavioral therapies and, when necessary, psychiatric drugs to minimize anxiety and aggressive behaviors.

    Now, new research is putting into question many of our beliefs about autism. The emerging paradigm is that the development of autism is influenced by the interaction of genes and the environment or what scientists call epigenetics. And while the symptoms of autism are largely brain based and behavioral, the disorder appears to be a whole body condition involving a number of systems, including the gastrointestinal, immune, and hormonal systems. There also appears to be more plasticity or ability of the brain of children with autism to change than was previously appreciated. This new view of autism offers both more hope and opportunities for research, prevention, and treatment.

     

    Environmental Factors Play a Larger Role in Determining Autism than Previously Recognized

    Previous studies looking at the genetic component of autism in twins estimated that about 90% of autism risk was due to genes and only 10% was due to environmental factors. Twin studies are often used in research to estimate what portion of an illness is due to hereditary factors or genes. The largest twin study of autism was done in 2012 at Stanford and found that genes accounted for only 38 percent of the autism risk and the remaining 62 percent was due to environmental factors. The study was published in the July 4, 2012 issue of the Archives of General Psychiatry.

    The environmental exposures contributing to autism are likely multiple, complex, and unique. It will be challenging for researchers to tease out the individual factors. So, what can be done now? It seems wise to recommend the ‘precautionary principle’ for both pregnant woman and young children, especially those with symptoms of autism. For example, avoiding or limiting exposure to toxins that are known to have adverse effects on health in early childhood may improve outcomes in some children who are sensitive to these exposures. At a larger public policy level, laws and regulations that protect pregnant woman and young children from these exposures may result in decreased rates of ASD in the population.

     

    Low Levels of Maternal Thyroid Hormone Linked to Autism Risk

    A recent study found that mothers who had lower levels of the thyroid hormone free thyroxine (T4) were more likely to have an autistic child by almost 4 fold. The study was published online in the August 2013 edition of the Annals of Neurology. Many people are familiar with the relationship of thyroid hormones to energy and weight gain. However, thyroid hormones are also critical for brain development, both during pregnancy and in early life. So, these findings are not surprising. In an earlier study published in 2011 in the journal, Autism Research, infants born with very low free T4 had an increased risk of autism.

    Why would some mothers and infants have lower levels of thyroid hormones? There are likely multiple possible causes, including low levels of dietary iodine, which is necessary for thyroid hormone production. Exposure to chemicals that can affect the thyroid gland is another possible cause of thyroid dysfunction. In a study published in the October 2011 edition of the Environmental Health Perspectives, researchers found that adults who had higher levels of urinary phthalates and bisphenol A (BPA), both components of plastics, had lower levels of thyroid hormones.

    For children diagnosed with autism, it may be wise to measure levels of thyroid hormones as part of a comprehensive evaluation. Low levels of thyroid hormones may be linked to both physical symptoms, such as constipation, and more severe delays in cognition and development.

    Treatment options for low thyroid hormones may include iodine, limiting exposure to chemicals known to affect the thyroid, and replacement therapy with thyroid hormone after further assessment by an endocrinologist

     

    Immune Changes in Autism are Associated with GI Symptoms and Repetitive Behaviors

    Numerous studies have implicated abnormalities in the immune system in children with autism. In a recent study published in the July 2012 edition of the journal, Brain, Behavior and Immunity, researchers found that children with autism had more dendritic cells, a type of immune cell. The researchers found that children with elevated dendritic cells also had more severe gastrointestinal symptoms and increased repetitive behaviors. Dendritic cells are involved in directing immune responses to microorganisms, such as infections or the bacteria that line our gastrointestinal tract. Previous studies have shown that children with autism have differences in the bacteria lining their gastrointestinal tracts, when compared to healthy children. These studies also highlight the importance of assessing and addressing immune and gastrointestinal disturbances in children with autism.

     

    Behavioral and Biological Therapies Can Improve Behaviors and Change the Brain in Autism Spectrum Disorders

    An intensive early intervention therapy among young children with autism not only improved their autism symptoms and social skills, but it also normalized brain activity when children with autism were viewing faces rather than objects, a response more similar to normal children. The intervention is called the Early Start Denver Model. The study author Sally Rogers, a professor of psychiatry and behavioral sciences at the UC Davis MIND institute, pointed out that the study demonstrates the potential for the brains of children with autism to develop and grow more normally. The study was published online in the October 26, 2012 edition of the Journal of the American Academy of Child & Adolescent Psychiatry.

    Biological treatments also have the potential to alter behaviors in autism and change the brain. In an article published in the April 2012 issue of Science Translational Medicine, an experimental drug called GRN-529 was found to increase social interactions and lessen repetitive behaviors in a mice model of autism. GNR-529 inhibits activity of a subtype of receptor protein for glutamate, an excitatory neurotransmitter.

    In study of a rat model of autism, Bacopa monniera, an herb with a long history of use in Ayurvedic medicine, was found to improve behaviors, decrease oxidative stress markers, and result in structural changes in the brain. The study was published in the May 2012 edition of Neurochemical Research. Interestingly, the rats in the study were induced to have autistic like symptoms after exposure to valproic acid, a medication associated with adverse effects during pregnancy. At least in an animal model, an herb that has a long history of safe use can be neuroprotective to the brain after exposure to an environmental insult.

    Emerging research is pointing to the need to look beyond assessing just behaviors in children with autism and also considering the functions of the hormonal, gastrointestinal, and immune systems. The best outcomes for children with autism may be from a combination of behavioral therapies alongside biomedical treatments to address dysfunctions in the various systems being implicated in autism.

     

                Suruchi Chandra, MD is a board-certified psychiatrist who uses an integrative approach to help children and adults with challenging psychological, behavioral, and medical issues.

                Dr. Chandra has an undergraduate degree from Harvard University and a medical degree from Yale University. She completed her residency in psychiatry at Massachusetts General Hospital/McLean Hospital combined program at Harvard Medical School.

                Dr. Chandra is a member of the Autism Research Institute think tank and has spoken at numerous conferences, including the Autism Research Institute, Talk About Curing Autism (TACA), the Advisory Board on Autism and Related Disorders, and the Autism Society of America.

     

    References

     

    1. Hallmayer J, et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry

    2. Román GC, et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Aug 13.

    3. Hoshiko S, Grether JK, Windham GC, Smith D, Fessel K. Are thyroid hormone concentrations at birth associated with subsequent autism diagnosis? Autism Res. 2011 Dec;4(6):456-63

    4. Meeker JD, Ferguson KK. Relationship between urinary phthalate and bisphenol A concentrations and serum thyroid measures in U.S. adults and adolescents from the National Health and Nutrition Examination Survey (NHANES) 2007-2008. Environ Health Perspect. 2011 Oct;119(10):1396-402

    5. Román GC, et al. Association of gestational maternal hypothyroxinemia and increased autism risk. Ann Neurol. 2013 Aug 13.

    6. Breece E, et al. Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors. Brain Behav Immun. 2013 Jul;31:69-75.

    7. Dawson G, et al. Early behavioral intervention is associated with normalized brain activity in young children with autism. J Am Acad Child Adolesc Psychiatry. 2012 Nov;51(11):1150-9. PMC3607427.

    8. Silverman JL, et al. Negative allosteric modulation of the mGluR5 receptor reduces repetitive behaviors and rescues social deficits in mouse models of autism. Sci Transl Med. 2012 Apr 25;4(131):131ra51.

    9. Sandhya T, et al.Bacopa monniera (L.) Wettst ameliorates behavioral alterations and oxidative markers in sodium valproate induced autism in rats. Neurochem Res. 2012 May;37(5):1121-31.

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