|Brain’s Fear Center Shrinks in Autism’s Most
Well Siblings Share Some of the Same Behavioral,
The brain’s fear hub likely becomes abnormally small in the most
severely socially impaired males with autism spectrum disorders
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.
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.
The 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, propose Richard Davidson, Ph.D., and colleagues
at the University of Wisconsin, who report on their magnetic resonance
imaging (MRI) study in the December 2006 Archives of General
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 percent 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 — in
this case, fear of people — 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.*** Children with autism who are
least hypersensitive to interaction with people would thus show
slower amygdala shrinkage while those who were most hypersensitive
would begin to show amygdala changes early in life. Such amygdala
adaptations likely affect most people with autism by adulthood,
according to the researchers. However, they caution that these
changes do not explain all autistic behavior, but account for slightly
more than half of the variability in nonverbal social impairment.
In the related study, published online in Biological Psychiatry,
October 24, 2006,**** Davidson, Kim Dalton,
Ph.D. and colleagues at the University of Wisconsin employed functional
magnetic resonance imaging (fMRI) as well as many of the same measures
used in the above study in 21 subjects with autism, 12 siblings
and 19 healthy controls. Notably, they found that unaffected siblings
of people with autism showed a similar pattern of smaller amygdalae,
and decreased eye fixation as their autistic siblings when looking
However, while the autism group showed reduced activation of a
face-processing area, the fusiform gyrus, on both sides of their
brains while performing a face-processing task, the well siblings
showed this difference only on the right side. This suggested an “intermediate
pattern” — that the well siblings were using circuitry similar
to healthy controls, but with some slight changes reminiscent of
their autistic siblings, but not as pervasive.
Similarly, eye fixation time did not predict amygdala activation
in the well siblings as it did in their autistic relatives. This
suggested that looking at faces did not boost activation of emotion-related
circuitry in the well siblings. Looking at eyes may not be a negative
experience for them, again suggesting an intermediate pattern.
Nonetheless, their amygdalae were about the same size as those
in the autism group.
The findings of both studies, taken together, suggest that measures
such as eye gazing time may prove useful in clarifying the relationship
between genes, brain and behavior in the autism spectrum, say the
Also participating in the Archives of General Psychiatry study
were: Kim Dalton, Ph.D., Tom Johnstone, Ph.D., Micah Long, Emelia
McAuliff, Terrence Oakes, Ph.D., Andrew Alexander, Ph.D., University
Also participating in the Biological Psychiatry study were: Brendon
Nacewicz, Andrew Alexander, Ph.D., University of Wisconsin.
The Archives study was also funded by NARSAD. The Biological Psychiatry
study was also funded by NARSAD and NAAR.
The National Institute of Mental Health (NIMH) mission is
to reduce the burden of mental and behavioral disorders through
research on mind, brain, and behavior.More information is available
at the NIMH website, http://www.nimh.nih.gov .
The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Web site at http://www.nichd.nih.gov/.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.