Klinefelter syndrome and risk of psychosis, autism and ADHD

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden. Electronic address: .
Journal of Psychiatric Research (Impact Factor: 3.96). 10/2013; 48(1). DOI: 10.1016/j.jpsychires.2013.10.001
Source: PubMed


Schizophrenia, bipolar disorder, autism spectrum disorders and ADHD might be overrepresented in Klinefelter syndrome, but previous investigations have yielded inconclusive results.
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.
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).
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.

148 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Sex chromosome aneuploidies are a common group of disorders that are characterised by an abnormal number of X or Y chromosomes. However, many individuals with these disorders are not diagnosed, despite established groups of core features that include aberrant brain development and function. Clinical presentations often include characteristic profiles of intellectual ability, motor impairments, and rates of neurological and psychiatric disorders that are higher than those of the general population. Advances in genetics and neuroimaging have substantially expanded knowledge of potential mechanisms that underlie these phenotypes, including a putative dose effect of sex chromosome genes on neuroanatomical structures and cognitive abilities. Continuing attention to emerging trends in research of sex chromosome aneuploidies is important for clinicians because it informs appropriate management of these common genetic disorders. Furthermore, improved understanding of underlying neurobiological processes has much potential to elucidate sex-related factors associated with neurological and psychiatric disease in general.
    The Lancet Neurology 03/2014; 13(3):306-318. DOI:10.1016/S1474-4422(13)70302-8 · 21.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: The aim of this study is to investigate emotional and behavioral problems among Indonesian patients with disorders of sex development (DSD) who recently came under clinical management. As diagnostic procedures and treatment had been delayed, patients progressively developed ambiguous bodies, difficult to conceal from outsiders. Method: We compared 118 Indonesian patients with DSD aged 6-41 years (60 children, 24 adolescents, 34 adults) and 118 healthy control subjects matched for age, gender, and residential settings. We used the Child Behavioral Checklist (CBCL), Youth Self-Report (YSR), and Adult Self-Report (ASR) to examine differences between patient and control groups as well as differences within patients groups. Results: On the CBCL, parents of young children with DSD reported significantly more emotional and behavioral problems than parents of matched control. Parents of daughters with CAH reported that their daughters withdrew themselves from social interactions. On the ASR, adults with DSD reported significantly more internalizing problems than controls, particularly anxiety and depression. No other differences in emotional functioning were found across different diagnostic groups. Conclusions: Indonesian patients with DSD who were untreated for most of their lives suffered more emotional and behavioral problems than matched controls. Differences and similarities between our findings and observations in patients from Western countries will be discussed.
    Journal of Psychosomatic Research 12/2014; 79(1). DOI:10.1016/j.jpsychores.2014.12.007 · 2.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuroimaging studies have shown that having an extra X chromosome is associated with abnormal structure and function of brain areas in the frontal lobe, which is crucially involved in executive functioning. However, there is little of knowledge of the type and severity of executive dysfunction, and the impact on emotional and behavioral problems. The present study aims to provide in this. In total, 40 children (23 boys with 47,XXY and 17 girls with 47,XXX) with an extra X chromosome and 100 non-clinical controls (47 boys and 53 girls) participated in the study. The participants were 9 to 18 years old. Processing speed and executive functioning were assessed using the Amsterdam Neuropsychological Testbattery (ANT) and the Dysexecutive Questionnaire (DEX). Problems in emotional and behavioral functioning were assessed with the Childhood Behavior Checklist (CBCL). Children with an extra X chromosome showed deficits in inhibition, mental flexibility, sustained attention and visual working memory. Parental report showed high levels of everyday manifestations of executive dysfunction. More severe inhibition difficulties were associated with higher levels of thought problems, aggression, and rule breaking behavior. Boys and girls with an extra X chromosome could not be differentiated based on severity of executive dysfunction, however girls had lower information processing speed than boys. These findings suggest that executive dysfunction may be part of the phenotype of children with an extra X chromosome, impacting the ability to function adequately in everyday life. Furthermore, children with impairments in inhibition may have more problems in regulating their thinking, emotions and behavior. This article is protected by copyright. All rights reserved.
    Genes Brain and Behavior 02/2015; 14(2). DOI:10.1111/gbb.12203 · 3.66 Impact Factor
Show more