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      Social functioning and emotion recognition in adults with triple X syndrome

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          Abstract

          Background

          Triple X syndrome (TXS) is caused by aneuploidy of the X chromosome and is associated with impaired social functioning in children; however, its effect on social functioning and emotion recognition in adults is poorly understood.

          Aims

          The aim of this study was to investigate social functioning and emotion recognition in adults with TXS.

          Method

          This cross-sectional cohort study was designed to compare social functioning and emotion recognition between adults with TXS ( n = 34) and an age-matched control group ( n = 31). Social functioning was assessed with the Adult Behavior Checklist and Social Responsiveness Scale for Adults. Emotion recognition was assessed with the Emotion Recognition Task in the Cambridge Neuropsychological Test Automated Battery. Differences were analysed by Mann-Whitney U-test.

          Results

          Compared with controls, women with TXS scored higher on the Adult Behavior Checklist, including the Withdrawn scale ( P < 0.001, effect size 0.4) and Thought Problems scale ( P < 0.001, effect size 0.4); and higher on the Social Responsiveness Scale for Adults, indicating impaired social functioning ( P < 0.001, effect size 0.5). In addition, women with TXS performed worse on the Emotion Recognition Task, particularly with respect to recognising sadness ( P < 0.005, effect size 0.4), fear ( P < 0.01, effect size 0.4) and disgust ( P < 0.02, effect size 0.3).

          Conclusions

          Our findings indicate that adults with TXS have a higher prevalence of impaired social functioning and emotion recognition. These results highlight the relevance of sex chromosome aneuploidy as a potential model for studying disorders characterised by social impairments such as autism spectrum disorder, particularly among women.

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          Most cited references48

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          Comparison of Sociodemographic and Health-Related Characteristics of UK Biobank Participants With Those of the General Population

          Abstract The UK Biobank cohort is a population-based cohort of 500,000 participants recruited in the United Kingdom (UK) between 2006 and 2010. Approximately 9.2 million individuals aged 40–69 years who lived within 25 miles (40 km) of one of 22 assessment centers in England, Wales, and Scotland were invited to enter the cohort, and 5.5% participated in the baseline assessment. The representativeness of the UK Biobank cohort was investigated by comparing demographic characteristics between nonresponders and responders. Sociodemographic, physical, lifestyle, and health-related characteristics of the cohort were compared with nationally representative data sources. UK Biobank participants were more likely to be older, to be female, and to live in less socioeconomically deprived areas than nonparticipants. Compared with the general population, participants were less likely to be obese, to smoke, and to drink alcohol on a daily basis and had fewer self-reported health conditions. At age 70–74 years, rates of all-cause mortality and total cancer incidence were 46.2% and 11.8% lower, respectively, in men and 55.5% and 18.1% lower, respectively, in women than in the general population of the same age. UK Biobank is not representative of the sampling population; there is evidence of a “healthy volunteer” selection bias. Nonetheless, valid assessment of exposure-disease relationships may be widely generalizable and does not require participants to be representative of the population at large.
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            Social cognitive dysfunction as a clinical marker: A systematic review of meta-analyses across 30 clinical conditions.

            Social cognition includes a range of cognitive processes that help individuals to understand how others think and feel. There is emerging evidence that social cognitive deficits may represent a transdiagnostic issue, potentially serving as a marker of neurological abnormality. We performed an electronic database search in order to identify published, peer-reviewed meta-analyses that compared facial emotion recognition or theory of mind task performance between individuals meeting clinical criteria for a psychiatric, neurological or developmental condition against healthy controls. We identified 31 meta-analyses eligible for inclusion that examined performance across relevant tasks among 30 different clinical populations. The results suggest that social cognitive deficits appear to be a core cognitive phenotype of many clinical conditions. Across the clinical groups, deficits in social cognitive domains were broadly similar in magnitude to those previously reported for more established aspects of cognition, such as memory and executive function. There is a need to clarify the 'real world' impact of these deficits, and to develop effective transdiagnostic interventions for those individuals that are adversely affected.
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              Sex-chromosome dosage effects on gene expression in humans

              Sex-chromosome dosage (SCD) effects on human gene expression are central to the biology of sex differences and sex-chromosome aneuploidy syndromes but are challenging to study given the cosegregation of SCD and gonadal status. We address this obstacle by systematically modeling SCD effects on genome-wide expression data from a large and rare cohort of individuals with diverse SCDs (XO, XX, XXX, XXXX, XY, XXY, XYY, XXYY, and XXXXY). Our findings update current models of sex-chromosome biology by ( i ) pinpointing a core set of X- and Y-linked genes with obligate SCD sensitivity, ( ii ) discovering several noncanonical modes of X-chromosome dosage compensation, and ( iii ) dissecting complex regulatory effects of X-chromosome dosage on large autosomal gene networks with key roles in cellular functioning. A fundamental question in the biology of sex differences has eluded direct study in humans: How does sex-chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex-chromosome aneuploidies (XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity among evolutionarily preserved X-Y homologs and update prevailing theoretical models for SCD compensation by detecting X-linked genes that increase expression with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex-chromosome genes regulate specific coexpression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. These gene coexpression results converge with analysis of transcription factor binding site enrichment and measures of gene expression in murine knockout models to spotlight the dosage-sensitive X-linked transcription factor ZFX as a key mediator of SCD effects on wider genome expression. Our findings characterize the effects of SCD broadly across the genome, with potential implications for human phenotypic variation.
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                Author and article information

                Journal
                BJPsych Open
                BJPsych Open
                BJO
                BJPsych Open
                Cambridge University Press (Cambridge, UK )
                2056-4724
                March 2021
                15 February 2021
                : 7
                : 2
                : e51
                Affiliations
                [1]Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University , The Netherlands; Department of Forensic Psychiatry & Mild Intellectual Disabilities, STEVIG, The Netherlands; and Department of Community Mental Health in Mild Intellectual Disabilities, Trajectum, The Netherlands
                [2]Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University , The Netherlands
                [3]Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University , The Netherlands
                [4]Department of Clinical Genetics and School for Oncology and Developmental Biology, Maastricht University Medical Centre , The Netherlands
                [5]Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University , The Netherlands
                [6]Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University , The Netherlands; Heeren Loo Zorggroep, The Netherlands; and Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centre , The Netherlands
                Author notes
                Correspondence: Dr Maarten Otter. Email: m.otter@ 123456maastrichtuniversity.nl
                Author information
                https://orcid.org/0000-0002-2113-6818
                https://orcid.org/0000-0002-6481-1094
                Article
                S2056472421000089
                10.1192/bjo.2021.8
                8058878
                33583482
                fea5ca03-5bce-43c0-bdc6-1e75d86f863e
                © The Author(s) 2021

                This is an Open Access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is unaltered and is properly cited. The written permission of Cambridge University Press must be obtained for commercial re-use or in order to create a derivative work.

                History
                : 01 August 2020
                : 23 December 2020
                : 27 December 2020
                Page count
                Figures: 2, Tables: 4, References: 48, Pages: 7
                Categories
                General Adult
                Papers

                triple x syndrome,autistic spectrum disorders,genetics,sex chromosomal disorder,emotion recognition

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