Otter claims that our finding of high levels of schizophrenia symptoms in XXY men is a rediscovery of what has been known for a long time. He supports his claim by referring to reports on triple X syndrome that were not published in peer-reviewed journals from the University of Gothenburg. We acknowledge that previous studies have also reported psychopathology in XXY men. However, we also point out that these studies have been limited in that they described men with Klinefelter's syndrome in psychiatric care or recorded hospital admissions. Our findings in a non-selected sample of XXY men, using valid and reliable dimensional measures of psychopathology, corroborate and extend the data derived from these earlier studies.
With regard to the novelty of the findings, it is interesting to note that none of the major reviews on Klinefelter's syndrome (Reference Smyth and BremnerSmyth & Bremner, 1998; Reference Lanfranco, Kamischke and ZitzmannLanfranco et al, 2004) report a vulnerability for schizophrenia psychopathology, indicating that this is not a generally accepted feature. In addition, the aim of our study was not to provide a comprehensive review of psychopathology in X chromosomal disorders, but we find the presence of schizophrenia psychopathology in XXX females very interesting as it supports our suggestion of a link between the X chromosome and schizophrenia symptoms.
Finally, Otter argues that reduced cerebral lateralisation in Klinefelter's syndrome has been suggested by neurobiological studies but is yet to be proved. However, a recent functional neuroimaging study has also presented evidence for reduced lateralisation in brain perfusion in XXY men (Reference Itti, Gaw Gonzalo and BooneItti et al, 2003).
In conclusion, we feel that the evidence put forward by Otter merely underscores the importance of our findings, as both triple X and Klinefelter's syndrome have been associated with schizophrenia symptoms. Including both syndromes in genetic studies would advance the understanding of a link between the X chromosome and schizophrenia pathology.
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