Amygdala volume and nonverbal social impairment in adolescent and adult males with autism.
BACKGROUND
Autism is a syndrome of unknown cause, marked by abnormal development of social behavior. Attempts to link pathological features of the amygdala, which plays a key role in emotional processing, to autism have shown little consensus.


OBJECTIVE
To evaluate amygdala volume in individuals with autism spectrum disorders and its relationship to laboratory measures of social behavior to examine whether variations in amygdala structure relate to symptom severity.


METHODS
We conducted 2 cross-sectional studies of amygdala volume, measured blind to diagnosis on high-resolution, anatomical magnetic resonance images. Participants were 54 males aged 8 to 25 years, including 23 with autism and 5 with Asperger syndrome or pervasive developmental disorder not otherwise specified, recruited and evaluated at an academic center for developmental disabilities and 26 age- and sex-matched community volunteers. The Autism Diagnostic Interview-Revised was used to confirm diagnoses and to validate relationships with laboratory measures of social function.


METHODS
Amygdala volume, judgment of facial expressions, and eye tracking.


RESULTS
In study 1, individuals with autism who had small amygdalae were slowest to distinguish emotional from neutral expressions (P=.02) and showed least fixation of eye regions (P=.04). These same individuals were most socially impaired in early childhood, as reported on the Autism Diagnostic Interview-Revised (P<.04). Study 2 showed smaller amygdalae in individuals with autism than in control subjects (P=.03) and group differences in the relation between amygdala volume and age. Study 2 also replicated findings of more gaze avoidance and childhood impairment in participants with autism with the smallest amygdalae. Across the combined sample, severity of social deficits interacted with age to predict different patterns of amygdala development in autism (P=.047).


CONCLUSIONS
These findings best support a model of amygdala hyperactivity that could explain most volumetric findings in autism. Further psychophysiological and histopathological studies are indicated to confirm these findings.
Nacewicz
Brendon M
BM
Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin-Madison, Waisman Center, 1500 Highland Avenue, Madison, WI 53705, USA.
Dalton
Kim M
KM
Johnstone
Tom
T
Long
Micah T
MT
McAuliff
Emelia M
EM
Oakes
Terrence R
TR
Alexander
Andrew L
AL
Davidson
Richard J
RJ
D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000473:pathology*; D020817:Asperger Syndrome / Q000175:diagnosis / Q000473:pathology / Q000523:psychology; D001321:Autistic Disorder / Q000175:diagnosis / Q000473:pathology* / Q000523:psychology; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000473:pathology / Q000523:psychology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000473:pathology* / Q000523:psychology; D004644:Emotions / Q000502:physiology; D005149:Facial Expression; D005403:Fixation, Ocular / Q000502:physiology; D006801:Humans; D007600:Judgment; D008279:Magnetic Resonance Imaging; D008297:Male; D009633:Nonverbal Communication / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D012919:Social Behavior; D012938:Social Perception; D014796:Visual Perception / Q000502:physiology