Smaller Brain Structures in Autism Linked to Social Deficits

MADISON, Wis., Dec. 5 -- Severe social deficits in males with autism has been traced by investigators here to shrinkage of the amygdala, the component of the limbic system that governs non-verbal responses to threats.

In a small study of eye-tracking and facial recognition in teens and young men with autism, those who were slowest at distinguishing emotional expressions had amygdalae that were smaller than normal in volume, reported Richard J. Davidson. Ph.D., of the University of Wisconsin.

The study participants who did worst at differentiating expressions turned out to have had the greatest degree of social impairment in childhood, the investigators reported in the December issue of the Archives of General Psychiatry.

"These results provide the first evidence for a link between objective measures of social impairment and amygdala structure in autism," the authors wrote.

"Amygdala volume not only predicts current deficits in processing facial emotions but also reflects early childhood impairment in nonverbal social behaviors estimated from retrospective diagnostic measures. This relatively time-independent degree of impairment interacts with age to predict abnormally small amygdala volumes by late adolescence in the most affected individuals."

The results are consistent with the theory, proposed by Bruce S. McEwen, Ph.D., of Rockefeller University in New York., that early hyperactivity of the amgydala can result in an overload of the structure that leads to subsequent shrinkage of the structure, Dr. Davidson and colleagues suggested.

"This initial hypertrophy and subsequent atrophy due to amygdala hyperactivity might be occurring at an early age in autism," they wrote.

The amygdala is known to be involved in emotion processing, but studies attempting to link amygdala volume to autism have been all over the map, with various studies showing normal, decreased, or increased volume in people with autism, the investigators noted.

They conducted two cross-sectional studies designed to determine amygdala volume in boys and young men with autism spectrum disorders, the relationship of amygdala volume to social behaviors, and whether variations in the structure could relate to severity of autistic symptoms.

The study population included 54 males from the ages of eight to 25. There were 23 with a diagnosis of autism, five Asperger's syndrome or pervasive developmental disorder not otherwise specified, and 26 age and gender-matched community volunteers.

Diagnoses of autism were confirmed with the Autism Diagnostic Interview-Revised.

The main outcomes measures were amygdala volume, judgment of facial expressions shown in photographs, and eye tracking.

In the first of the two studies, the authors found that the participants with autism who had small amygdalae as determined by standardized high-resolution MRI, were significantly slower than others to distinguish emotional expression from neutral expressions in the photographs (P=0.02).

In addition, these participants showed the least eye fixation (P=0.04), suggesting poor judgment of facial expressions, and turned out to have been the most socially impaired in early childhood as determined by the Austism Diagnostic Interview-Revised (P<0.04), the authors reported.

In the second study that authors found that the participants with autism had significantly smaller amygdalae than controls (P=0.03), as well as group differences in the relation between amygdala volume and age.

The results of this study also showed, similar to the first study, that participants with autism and the smallest amygdalae by volume had more gaze avoidance and larger degrees of social impairment in childhood.

"Across the combined sample, severity of social deficits interacted with age to predict different patterns of amygdala development in autism (P=0.047)," the investigators noted.

In a study published Oct. 24 in the online edition of Biological Psychiatry, Dr. Davidson and colleagues reported that compared with controls, unaffected siblings of people with autism share some of the same differences in amygdala volume, facial processing, and brain activation.

"Together, these results provide the first evidence linking objective measures of social impairment and amygdala structure and related brain function in autism," Dr. Davidson said. "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."

The authors pointed out however that amygdala volume does not determine all autistic behavior. "In this study, amygdala volume did not correlate with verbal or repetitive behaviors and predicted, at most, 53% of the variance in nonverbal social impairment," they wrote. "Abnormalities of hippocampus, cerebellum, superior temporal cortex, and prefrontal cortex and the white matter connecting these regions are all likely involved in autism.

They also noted that "our study was limited to males aged eight years to early adulthood and, therefore, does not address relationships between amygdala volume and autistic behavior in younger children or in females."

The study was supported by grants from the National Institute of Mental Health, National Alliance for Research on Schizophrenia and Affective Disorders, and the National Institute of Child Health and Human Development.