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From the Stanford Psychiatry Neuroimaging Laboratory, Department of Psychiatry and Behavioral Sciences (A.J. Patwardhan, and Drs. Eliez and Reiss), Stanford University School of Medicine, CA; and the Department of Pediatrics (Dr. Bender and M.G. Linden), National Jewish Medical and Research Center, Denver, CO.
Address correspondence and reprint requests to Dr. Allan L. Reiss, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Stanford, CA 94305-5719.
OBJECTIVE: This study focuses on variation in brain morphology associated with supernumerary X chromosome and Klinefelter syndrome (KS). Using an unselected birth cohort of KS subjects and high-resolution MRI, the authors investigated the neuroanatomic consequences of the 47,XXY karyotype in the presence and absence of exogenous testosterone supplementation.
METHODS: Regional brain volumes were measured in 10 subjects with KS and 10 age-matched control men. Five of the KS subjects had received testosterone supplementation since puberty (KS+T) and five had not (KS-T).
RESULTS: KS subjects showed significant (p < 0.01) reduction in left temporal lobe gray matter volumes compared with normal control subjects. Differences in left temporal gray volumes were also significant between the KS+T and KS-T groups (p < 0.01). Verbal fluency scores were significantly different between the KS+T and KS-T groups as well.
CONCLUSION: Supernumerary X chromosome material in men is associated with a reduction in left temporal lobe gray matter, a finding that is consistent with the verbal and language deficits associated with KS. Also, relative preservation of gray matter in the left temporal region is associated with exposure to exogenous androgen during development. A history of testosterone supplementation also appears to be associated with increased verbal fluency scores in KS patients.
Key words: Brain morphology—Klinefelter syndrome—Extra X chromosome—Testosterone supplementation.
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