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 Psychiatry.*
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 amydalae 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 4 times longer looking at eyes
that 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 at faces.
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 researchers.
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 of
Wisconsin.
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.
* Nacewicz BM, Dalton KM, Johnstone T, Long MT, McAuliff EM,
Oakes TR, Alexander AL, Davidson RJ. Amygdala volume and nonverbal social
impairment in adolescent and adult males with autism. Arch Gen
Psychiatry. 2006 Dec;63(12).
** Dalton KM, Nacewicz BM, Johnstone T, Schaefer HS, Gernsbacher
MA, Goldsmith HH, Alexander AL, Davidson RJ. Gaze fixation and the neural circuitry of face processing in autism.
Nat Neurosci. 2005 Apr;8(4):519-26. Epub 2005 Mar 6.
*** McEwen BS. Mood disorders and allostatic load. Biol Psychiatry.
2003 Aug 1;54(3):200-7. Review.
**** Dalton KM, Nacewicz BM, Alexander AL, Davidson RJ.
Dalton KM, Nacewicz BM, Alexander AL, Davidson RJ. Gaze-Fixation, Brain Activation, and Amygdala Volume in Unaffected
Siblings of Individuals with Autism.
Biol Psychiatry.
2006 Oct 24; [Epub ahead of print]
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.
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 NICHD website.
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.
View Full Article
Reprinted with the permission of the National Institute of Mental Health. © 2008 NIMH.
Celebrate Memorial Day! Worksheets and Activities About American History 
May Workbooks are Here! 
