Effects of an extra X chromosome on language lateralization: an fMRI study with Klinefelter men (47,XXY)

De novo occurring genetic variations provide an opportunity to study the effects of genes on structure and function of the brain. The presence of an extra X chromosome in men (XXY karyotype) has been associated with language deficits. Recently, schizophrenia spectrum traits have been observed in XXY men, which is of interest as language deficits are prominent in schizophrenia. One possible neural mechanism underlying these deficits is reduced hemispheric specialization for language. However, there has been no study of brain activity patterns during language processing in XXY men. Also, it remains unclear whether reduced language lateralization may be related to mental functioning in these men. We used functional Magnetic Resonance Imaging (fMRI) to study language lateralization in 15 XXY men as compared to 14 control men. We used a psychiatric interview and a schizotypy questionnaire to explore the relation between language lateralization and mental functioning in these men, with special interest in disorganization of thought and language. Compared to controls, the XXY group showed reduced hemispheric specialization for language, which was due to decreased functional asymmetry in the superior temporal gyrus (STG) and the supramarginal gyrus (part of Wernicke's area). Reduced lateralization in the STG correlated significantly with disorganization traits. These findings suggest the X chromosome may be involved in hemispheric specialization for language. Moreover, reduced hemispheric specialization for language processing in the superior temporal gyrus may have important consequences for mental functioning, as it was associated with disorganization of thought and language as seen in the schizophrenia spectrum.