Am J Psychiatry 161:539-546, March 2004
© 2004 American Psychiatric Association
Neuroanatomic Variation in Monozygotic Twin Pairs Discordant for the Narrow Phenotype for Autism
Wendy R. Kates, Ph.D.,
Courtney P. Burnette, M.S.,
Stephan Eliez, M.D.,
Leslie Abbott Strunge, M.A.,
Desmond Kaplan, M.D.,
Rebecca Landa, Ph.D.,
Allan L. Reiss, M.D., and
Godfrey D. Pearlson, M.D.
OBJECTIVE: The broader autism phenotype includes relatives of individuals with autism who display social and language deficits that are qualitatively similar to those of autism but less severe. In previous studies of monozygotic twins discordant for autism, more than 75% of the twins without autism displayed the broader phenotype. Differences in neuroanatomy between discordant monozygotic twins might be associated with the narrow and broader behavioral phenotypes. The authors examined the relationship of twin pair differences in clinical phenotype to differences in neuroanatomic phenotype. METHOD: The subjects were 16 monozygotic twin pairs between the ages of 5 and 14 years and 16 matched singleton comparison subjects. Seven twin pairs were clinically concordant and nine twin pairs were clinically discordant for strictly defined autism. After magnetic resonance imaging, a semiautomated procedure was applied to images in which the brain tissue was subdivided into neurofunctional regions and segmented into gray, white, and ventricular compartments. RESULTS: Both the concordant and discordant twin pairs exhibited concordance in cerebral gray and white matter volumes. However, only the clinically concordant pairs exhibited concordance in cerebellar gray and white matter volumes. Within the discordant twin pairs, both the twins with autism and their co-twins exhibited frontal, temporal, and occipital white matter volumes that were lower than those of the comparison subjects. CONCLUSIONS: These findings support the role and the limits of genetic liability in autism. Continuing to clarify the neuroanatomic pathways in autistic spectrum disorders could illuminate the etiology of autism and, ultimately, contribute to treatments.
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