Abnormal Growth of the Amygdala in Infants Tied to Autism

A new study suggests that overgrowth of the amygdala in infants during the first 6 to 12 months of life is tied to a later diagnosis of autism spectrum disorder (ASD).

“The faster the amygdala grew in infancy, the more social difficulties the child showed when diagnosed with autism a year later,” first author Mark Shen, PhD, assistant professor of psychiatry and neuroscience, University of North Carolina, Chapel Hill, told Medscape Medical News.

The study was published online March 25 in the American Journal of Psychiatry.

Unique to Autism

The amygdala plays a key role in processing memory, emotional responses, and decision-making.

It’s long been known that the amygdala is abnormally large in school-aged children with ASD, but until now, it was not known precisely when aberrant amygdala growth happens, what the clinical consequences may be, and whether amygdala overgrowth is unique to autism.

To investigate, Shen and colleagues evaluated 1099 longitudinal MRI scans obtained during natural sleep at 6, 12, and 24 months of age in 408 infants in the Infant Brain Imaging Study (IBIS) Network.

The cohort included 58 infants at high likelihood of developing ASD who were later diagnosed with the disorder, 212 infants at high likelihood of ASD who did not develop ASD, 109 typically-developing control infants, and 29 infants with fragile X syndrome.

At 6 months, infants who developed ASD had typically sized amygdala volumes, but showed significantly faster amygdala growth between 6 and 24 months, such that by 12 months the ASD group had a significantly larger amygdala volume (Cohen’s d = 0.56) compared with all other groups .

Amygdala growth rate between 6 and 12 months was significantly associated with greater social deficits at 24 months when the children were diagnosed with ASD.

“We found that the amygdala grows too rapidly between 6 and 12 months of age, during a presymptomatic period in autism, prior to when the diagnostic symptoms of autism (social difficulties and repetitive behaviors) are evident and lead to the diagnosis later of autism, Shen told Medscape Medical News.

This brain growth pattern appears to be unique to autism, as babies with the genetic disorder fragile X syndrome — another neurodevelopmental condition — showed a markedly different brain growth pattern: no differences in amygdala growth but enlargement of a different brain structure, the caudate, which was linked to increased repetitive behaviors, the investigators found.

Earlier Intervention

Prior research has shown that children who are later diagnosed with ASD often display problems in infancy with how they attend to visual stimuli in their surroundings.

These early problems with processing visual and sensory information may put increased stress on the amygdala, potentially leading to amygdala hyperactivity, deficits in pruning dendritic connections and overgrowth, Shen and colleagues hypothesize.

Amygdala overgrowth has also been linked to chronic stress in studies of other psychiatric conditions, such as depression and anxiety, and may provide a clue to understanding this observation in infants who later develop autism.

This research suggests that an optimal time to begin supports for children who are at the highest likelihood of developing autism may be during the first year of life: to improve early precursors to social development difficulties, such as sensory processing, in babies even before social development arise,” Shen said.

Commenting for Medscape Medical News, Cyrus A. Raji, MD, PhD, assistant professor of radiology and neurology, Washington University in St. Louis, Missouri, said, “What makes this study important is the finding of abnormally increased amygdala growth rate in autism using a longitudinal design that focuses on earlier development.”

“While we are typically used to understanding brain structure as abnormally decreasing over time in certain disorders like Alzheimer’s disease, this study challenges us to understand that too much brain volume growth can also be abnormal in specific conditions,” Raji added.

This research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, and National Institute of Mental Health, along with Autism Speaks and the Simons Foundation. Shen and Raji ha ve disclosed no relevant financial relationships.

Am J Psychiatry. Published online March 25, 2022. Full text

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