Klinefelter syndrome and risk of psychosis, autism and ADHD
Introduction
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.
Section snippets
Method
We used the National Patient Register (Ludvigsson et al., 2011) to identify 860 Klinefelter patients coded according to the ICD-10 (1997 and onwards, inpatient or out-patient diagnoses of Q98.0-Q98.2, Q98.4). Individuals with schizophrenia (ICD-8: 295.0–295.6, 295.8, 295.9; ICD-9: 295A–295G, 295W, 295X; ICD-10: F20) and bipolar disorder, defined according to a validated algorithm by Sellgren et al. (2011), were also identified through the National Patient Register. Individuals with autism
Results
The number of individuals with Klinefelter syndrome, schizophrenia, bipolar disorder, autism spectrum disorder and ADHD identified from the Swedish registers are presented in Table 1.
The results from the conditional logistic regressions are shown in Table 2. Individuals with Klinefelter syndrome had 3.6–3.8 times higher risks of having a diagnosis of schizophrenia or bipolar disorder and 5.6–6.2 times higher risks of having autism spectrum disorder or ADHD, compared with controls.
Discussion
We found that Klinefelter patients had a nearly four times higher risk of being diagnosed with schizophrenia and bipolar disorder and an about six times higher risk of autism spectrum disorder and ADHD. These findings are consistent with most prior investigations (DeLisi et al., 1994, Van Rijn et al., 2006, Bojesen et al., 2006, Bruining et al., 2009). Given the relatively high prevalence of Klinefelter syndrome, clinicians should be aware of the possibility of the syndrome in a proportion of
Contributors
MC performed the analyses and wrote the first version of this manuscript. AOG contributed in the write-up of the manuscript. MB wrote the programs that the analyses are based on and HL contributed with issues pertaining to classifications of disorders. ES and NL contributed with valuable comments on the clinical significance of the results and were parts in the write-up of the final version of the manuscript. ML and PL contributed with advices regarding the study design and sampling procedure
Declaration of interest
None.
Funding
None.
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