From a Disabling Condition to a Variant of Normalcy: Neuropsychiatric Aspects.

Current studies suggest an elevated risk of developing psychiatric disorders among individuals with XXY, though the emerged symptoms are described as heterogeneous, atypical, and frequently transnosographic. The personality and behavior of Klinefelter syndrome (KS) patients have been described as shy, reserved, sensitive, and passive in childhood, which, jointly with neglected learning difficulties, may lead to secondary adaptation and behavioral problems during adolescence. The neuropsychological phenotype in adults affected by KS is highly variable. Impaired measures of verbal skills, high incidence of dyslexia, and social dysfunctions are among the most consistently reported behavioral phenotypes. KS patients may primarily manifest difficulties in social adjustment and in coping with social situations. Indeed, high levels of distress during social interactions are consistent with reports of social anxiety, social withdrawal, and shyness. In addition, studies on KS boys and adults unselected for psychiatric disorders support an increased prevalence of schizotypal traits, schizophrenia symptoms, and disorders that comprise psychosis, depression, anxiety, autism spectrum, and attention deficit/hyperactivity (ADHD). Anxiety and depression, along with low self-esteem and closure, are the most prevalent and debilitating affective symptoms among KS patients, while associations with bipolar disorders have rarely been reported. On the whole, research on KS patients shows that depression has a significant negative effect on the quality of life, in addition to being a leading cause of disability and a major risk factor for suicide. Treatment of Klinefelter syndrome requires to be analyzed in more depth to ascertain which intervention, psychological and/or pharmacological, proves to be the most helpful for patients to achieve more effective coping and adaptation to disease, as well as to ameliorate psychopathological symptoms and quality of life. All KS patients should receive a comprehensive psychological or psychiatric assessment to manage the increased risk of anxiety, depression, and psychosis or behavioral disorders. Group psychotherapy could be beneficial to KS patients for expressing and sharing their sense of shame and isolation and for getting the support of peers. Psychological intervention as well would be helpful in executing the most profitable strategies to enhance the poor pharmacological compliance of KS subjects

Sex differences in DNA methylation assessed by 450 K BeadChip in newborns

BACKGROUND: DNA methylation is an important epigenetic mark that can potentially link early life exposures to adverse health outcomes later in life. Host factors like sex and age strongly influence biological variation of DNA methylation, but characterization of these relationships is still limited, particularly in young children. METHODS: In a sample of 111 Mexican-American subjects (58 girls , 53 boys), we interrogated DNA methylation differences by sex at birth using the 450 K BeadChip in umbilical cord blood specimens, adjusting for cell composition. RESULTS: We observed that ~3 % of CpG sites were differentially methylated between girls and boys at birth (FDR P < 0.05). Of those CpGs, 3031 were located on autosomes, and 82.8 % of those were hypermethylated in girls compared to boys. Beyond individual CpGs, we found 3604 sex-associated differentially methylated regions (DMRs) where the majority (75.8 %) had higher methylation in girls. Using pathway analysis, we found that sex-associated autosomal CpGs were significantly enriched for gene ontology terms related to nervous system development and behavior. Among hits in our study, 35.9 % had been previously reported as sex-associated CpG sites in other published human studies. Further, for replicated hits, the direction of the association with methylation was highly concordant (98.5–100 %) with previous studies. CONCLUSIONS: To our knowledge, this is the first reported epigenome-wide analysis by sex at birth that examined DMRs and adjusted for confounding by cell composition. We confirmed previously reported trends that methylation profiles are sex-specific even in autosomal genes, and also identified novel sex-associated CpGs in our methylome-wide analysis immediately after birth, a critical yet relatively unstudied developmental window. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-2034-y) contains supplementary material, which is available to authorized users

Novel associations between blood DNA methylation and body mass index in middle-Aged and older adults

Background/Objectives:There is increasing evidence of a relationship between blood DNA methylation and body mass index (BMI). We aimed to assess associations of BMI with individual methylation measures (CpGs) through a cross-sectional genome-wide DNA methylation association study and a longitudinal analysis of repeated measurements over time.Subjects/Methods:Using the Illumina Infinium HumanMethylation450 BeadChip, DNA methylation measures were determined in baseline peripheral blood samples from 5361 adults recruited to the Melbourne Collaborative Cohort Study (MCCS) and selected for nested case-control studies, 2586 because they were subsequently diagnosed with cancer (cases) and 2775 as controls. For a subset of 1088 controls, these measures were repeated using blood samples collected at wave 2 follow-up, a median of 11 years later; weight was measured at both time points. Associations between BMI and blood DNA methylation were assessed using linear mixed-effects regression models adjusted for batch effects and potential confounders. These were applied to cases and controls separately, with results combined through fixed-effects meta-Analysis.Results:Cross-sectional analysis identified 310 CpGs associated with BMI with P<1.0 × 10 â '7, 225 of which had not been reported previously. Of these 225 novel associations, 172 were replicated (P<0.05) using the Atherosclerosis Risk in Communities (ARIC) study. We also replicated using MCCS data (P<0.05) 335 of 392 associations previously reported with P<1.0 × 10 â '7, including 60 that had not been replicated before. Associations between change in BMI and change in methylation were observed for 34 of the 310 strongest signals in our cross-sectional analysis, including 7 that had not been replicated using the ARIC study.Conclusions:Together, these findings suggest that BMI is associated with blood DNA methylation at a large number of CpGs across the genome, several of which are located in or near genes involved in ATP-binding cassette transportation, tumour necrosis factor signalling, insulin resistance and lipid metabolism