سندروم کلاین فلتر و خطر روان پریشی، اوتیسم و اختلال کم توجهی- بیش فعالی (ADHD)

Background Schizophrenia, bipolar disorder, autism spectrum disorders and ADHD might be overrepresented in Klinefelter syndrome, but previous investigations have yielded inconclusive results. Methods We compared a national sample of 860 Klinefelter patients in Sweden with 86 000 matched population controls. To assess the risks of schizophrenia, bipolar disorder, autism spectrum disorder and ADHD in Klinefelter patients, we estimated odds ratios and 95% confidence intervals using conditional logistic regressions. Results Klinefelter patients had almost four times higher risks of schizophrenia, odds ratio (OR) = 3.6, 95% confidence interval (CI) 2.0–6.7 and bipolar disorder (OR = 3.8, CI 1.8–7.6) and about six times higher risk of autism spectrum disorder (OR = 6.2, CI 4.0–9.4) and ADHD (OR = 5.6, CI 4.0–7.8). Conclusions The risk of psychosis, autism and ADHD is increased in Klinefelter patients. These findings indicate an X chromosome-related factor in the etiology of the studied psychiatric disorders, and may also have implications for treatment of patients with Klinefelter syndrome.

Klinefelter syndrome is characterized by an extra X chromosome, usually resulting in the 47, XXY karyotype. It is the most common sex chromosome aberration and affects about 1 in 670 men (Bojesen et al., 2003). Previous research suggests that psychiatric disorders might be overrepresented in Klinefelter patients; several case reports describe concurrence with schizophrenia and bipolar disorder (DeLisi et al., 1994). In the same vein, Van Rijn et al. (2006) reported a significantly higher mean level of schizotypal traits among 36 men compared with controls. Further, in 51 boys aged 6–19 years, 12% met diagnostic criteria for a psychotic disorder, 27% had an autism spectrum disorder and 63% had ADHD (Bruining et al., 2009). The risk of psychosis in Klinefelter patients has also been investigated in two studies based on Danish population registers, where the first found no evidence of an increased risk of schizophrenia or bipolar disorder (Mors et al., 2001), whereas the second found a five times higher risk of broadly defined psychosis (Bojesen et al., 2006). Taken together, prior findings suggest that X chromosomal abnormalities may be involved in increased liability to schizophrenia, bipolar disorder, autism spectrum disorders and ADHD, but the status of the associations remain somewhat unclear. We wanted to test the hypothesis that diagnoses of schizophrenia, bipolar disorder, autism spectrum disorders and ADHD are more common among Klinefelter patients in a Swedish population-based setting.