Brain's fear center smaller in most severely socially-impaired males with autism spectrum disorders

January 12, 2007

Researchers funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) and National Institute on Child Health and Human Development (NICHD) have discovered that the brain's fear hub likely becomes abnormally small in the most severely socially-impaired males with autism spectrum disorder. New findings suggest that social fear in autism may initially trigger a hyperactive, abnormally enlarged amygdala, which eventually gives way to a toxic adaptation that kills amygdala cells and shrinks the structure, said Richard Davidson, Ph.D., and colleagues at the University of Wisconsin.

Researchers funded by the National Institutes of Health's (NIH) National Institute of Mental Health (NIMH) and National Institute on Child Health and Human Development (NICHD) have discovered that the brain's fear hub likely becomes abnormally small in the most severely socially-impaired males with autism spectrum disorder. New findings suggest that social fear in autism may initially trigger a hyperactive, abnormally enlarged amygdala, which eventually gives way to a toxic adaptation that kills amygdala cells and shrinks the structure, said Richard Davidson, Ph.D., and colleagues at the University of Wisconsin.

Teens and young men who were slowest at distinguishing emotional from neutral expressions and gazed at eyes least—indicators of social impairment—had a smaller than normal amygdala, an almond-shaped danger-detector deep in the brain. The researchers also linked such amygdala shrinkage to impaired nonverbal social behavior in early childhood.

In a related study, another research team led by Davidson found that well siblings of people with autism share some of the same differences in amygdala volume, and in the way they look at faces and activate social/emotional brain circuitry, particularly an area critical for face processing.

"Together, these results provide the first evidence linking objective measures of social impairment and amygdala structure and related brain function in autism," explained Davidson. "Finding many of the same differences, albeit more moderate, in well siblings helps to confirm that autism is likely the most severe expression of a broad spectrum of genetically-influenced characteristics."

While some people with minimal expression of these traits might be perceived as aloof or loners, those at the more severe end of the spectrum are unable to engage in give-and-take interactions and fail to develop age-appropriate peer relationships. Notably, they shy away from looking at eyes. Davidson's research team had reported last year linked such eye-gazing with hyperactivation of their fear hub. Yet different studies have found the amygdala in autism to be variously enlarged, shrunken or even normal in size.

Davidson, Kim Dalton and colleagues suspected that these seemingly inconsistent findings resulted from the wide variability of the autism spectrum, which masked amygdala changes—that a clearer picture would emerge if the length and severity of hypersensitivity to social interactions were factored in. They brought to bear eye-tracking and other measures of facial emotion processing in combination with MRI to find out if degree of non-verbal social impairment might predict amygdala volume in 49 males, aged 8-25, including 25 with autism spectrum disorders.

Those in the autism group who had a small amygdala were significantly slower at identifying happy, angry, or sad facial expressions, and spent the least time looking at eyes relative to other facial regions. Autistic subjects with the smallest amygdalae took 40% longer than those with the largest fear hubs to recognize such emotional facial expressions, and those with the largest amygdalae spent about four times longer looking at eyes than those with the smallest. Eye fixation did not correlate with amygdala volume among 24 control subjects. The size of the amygdala increased early in autism group subjects with normal eye fixation, while it increased little in those with low eye fixation. Moreover, autism group subjects with small amygdalae had the most non-verbal social impairment as children.

The researchers suggest that the amygdala in autism fits a model in which a brain structure adapts to chronic stress by first becoming hyperactive, but over time succumbing to a process of toxic cell death and atrophy, as has been proposed occurs in the hippocampus for some forms of depression. The results are in the December 2006 issue of Archives of General Psychiatry.