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Anxiety, the Amygdala, and Autism

Alycia Halladay, PhD
Autism Science Foundation
Thomas Avino, PhD
Cyndi Schumann, PhD
University of California, Davis
Date Published: 
June 21, 2018

One of the more common and distressing co-occurring mental health issues in people with autism spectrum disorder (ASD) is anxiety. Anxiety disorders are present in at least 50% of people with ASD, and some estimates go as high as 80%.1-4 The relationship between anxiety and autism is complex, and it is often difficult to disentangle symptoms of anxiety from symptoms of autism. Think about social problems in autism. Are they due to social anxiety, lack of interest, lack of competence in social interaction, or all of those factors?

Anxiety has been a hot topic in autism research because while there are no medical treatments for the core symptoms of autism, there are many behavioral and pharmacological treatments for anxiety. Treating the anxiety related to autism can greatly improve quality of life.

There has been an enormous amount of research on the neurobiology of fear and anxiety, much of which is carried out in animal models such as mice. For example, an area of the brain called the amygdala has been shown to be strongly related to fear and anxiety symptoms.5 Anxiety and fear are both normal responses, that, from an evolutionary perspective, are there to protect the organism. The amygdala has often been called a "danger detector"; and is crucial for the survival of the individual and the species. Many neuroscientists have speculated that abnormal activity of the amygdala may lead to anxiety or a sense of fear when there is no danger present. Given the link of anxiety to autism, it should not be surprising that there is substantial evidence that the structure and function of the amygdala in autism is altered.

Some of the strongest evidence for an altered amygdala in autism has come recently from postmortem brain analysis from the Schumann laboratory at the University of California, Davis. This was made possible by families who made the decision to donate the brains of their loved ones to research after they had passed away. Specifically, Avino and his colleagues6 found that in typically developing people, the number of neurons in the amygdala increases throughout childhood into adulthood. This is unusual in its own right because there are few brain regions that increase their neuron number after birth. What was striking in this study was that the number of neurons in the amygdala from individuals with autism was higher in young children, but lower in adults. As seen from the graph, compared to people who are typically developing (NT), there are 11% more neurons in the amygdala of young children with ASD, but 20% fewer neurons in adults with ASD.6 These findings significantly expanded on previous investigations of the amygdala in autism.7,8

What causes this abnormal trajectory of development in the autistic amygdala? How does this altered development relate to anxiety in people with autism? These are questions that will need further research to answer. However, because of the generous donations of brain tissue by families of individuals with autism, as well as typical individuals, we are beginning to understand the neuropathology of ASD. With understanding comes the potential for developing targeted treatments. Because these changes in the amygdala occur after the child is born, this research may have identified an early critical window for intervention.

If you are interested in learning more about Autism BrainNet and the studies that are possible because of this resource, please go to www.takesbrains.org/signup.

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References: 
  1. Kent R, Simonoff E. Chapter 2 - Prevalence of Anxiety in Autism Spectrum Disorders. In: Kerns CM, Renno P, Storch EA, Kendall PC, Wood JJ, eds. Anxiety in Children and Adolescents with Autism Spectrum Disorder: Academic Press; 2017:5-32.
  2. Lecavalier L, Wood JJ, Halladay AK, et al. Measuring anxiety as a treatment endpoint in youth with autism spectrum disorder. Journal of autism and developmental disorders. 2014;44(5):1128-1143.
  3. Postorino V, Kerns CM, Vivanti G, Bradshaw J, Siracusano M, Mazzone L. Anxiety Disorders and Obsessive-Compulsive Disorder in Individuals with Autism Spectrum Disorder. Curr Psychiatry Rep. 2017;19(12):92.
  4. Maddox BB, White SW. Comorbid Social Anxiety Disorder in Adults with Autism Spectrum Disorder. Journal of autism and developmental disorders. 2015;45(12):3949-3960.
  5. Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron. 2005;48(2):175-187.
  6. Avino TA, Barger N, Vargas MV, et al. Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism. Proc Natl Acad Sci U S A. 2018;115(14):3710-3715.
  7. Morgan JT, Barger N, Amaral DG, Schumann CM. Stereological study of amygdala glial populations in adolescents and adults with autism spectrum disorder. PloS one. 2014;9(10):e110356.
  8. Wegiel J, Flory M, Kuchna I, et al. Stereological study of the neuronal number and volume of 38 brain subdivisions of subjects diagnosed with autism reveals significant alterations restricted to the striatum, amygdala and cerebellum. Acta neuropathologica communications. 2014;2:141.