What's in a face?: the early developmental impact of Sex Chromosome Trisomies (XXX, XXY, XYY) on social cognition

This thesis describes the impact of Sex Chromosome Trisomies (SCT; XXX, XXY, XYY) on early social cognition. Individuals with SCT have an increased vulnerability for developing challenges on the social domain, given the convergent impact of the X and Y chromosome on brain networks that underly social adaptive development. We found that already from a very early age on, SCT can be associated with increased risk for vulnerabilities in social interactions, and with increased levels of social impairments associated with ASD. These findings suggest that SCT impact the maturation of the social brain already from an early age, and stresses the importance of early routine monitoring and (preventive) support of early social development in young children with SCT.NWOEducation and Child Studie

Early preventive intervention for young children with sex chromosome trisomies (XXX, XXY, XYY): supporting social cognitive development using a neurocognitive training program targeting facial emotion understanding

Education and Child Studie

The impact of sex chromosome trisomies (XXX, XXY, XYY) on early social cognition: social orienting, joint attention, and theory of mind

Objective: About 1:650–1,000 children are born with an extra X or Y chromosome (XXX; XXY; XYY), which results in a sex chromosome trisomy (SCT). This study aims to cross-sectionally investigate the impact of SCT on early social cognitive skills. Basic orienting toward social cues, joint attention, and theory of mind (ToM) in young children with SCT were evaluated. Method: About 105 children with SCT (range: 1–7 years old) were included in this study, as well as 96 age-matched nonclinical controls. Eyetracking paradigms were used to investigate the eye gaze patterns indicative of joint attention skills and orienting to social interactions. The ToM abilities were measured using the subtest ToM of the Developmental NEuroPSYchological Assessment, second edition, neuropsychological test battery. Recruitment and assessment took place in the Netherlands and in the United States. Results: Eyetracking results revealed difficulties in children with SCT in social orienting. These difficulties were more pronounced in children aged 3 years and older, and in boys with 47,XYY. Difficulties in joint attention were found over all age groups and karyotypes. Children with SCT showed impairments in ToM (26.3% in the [well] below expected level), increasing with age. These impairments did not differ between karyotypes. Conclusions: An impact of SCT on social cognitive abilities was found already at an early age, indicating the need for early monitoring and support of early social cognition. Future research should explore the longitudinal trajectories of social development in order to evaluate the predictive relationships between social cognition and outcome later in life in terms of social functioning and the risk for psychopathology.NWO016.165.397Development Psychopathology in context: clinical setting

Early impact of X- and Y-chromosome variations (XXX, XXY, XYY) on social communication and social emotional development in 1–2-year-old children

Sex chromosome trisomies (SCTs) are characterized by an extra X- or Y-chromosome(XXX, XXY, XYY). The present study aims to investigate early signs of social communica-tion and social emotional development in veryyoung children with SCT. Thirty-four chil-dren with SCT (aged 12–24 months) were included in this study, as well as 31 age-matched controls. Social communication was measured with structured behavior observa-tions according to the Early Social Communication Scales, and social emotional develop-mental level with the Bayley Social Emotional parental questionnaire. Recruitment andassessment took place in the Netherlands and in the United States. On average, 12–24-montholdchildrenwithSCTshoweddifficulties with early social communication, moreso in responding to others as compared to initiating social communications. During socialinteractions, children with SCT made less frequent eye contact, compared to controls.Also, difficulties in acquiring social emotional milestones were found in 1-year old childrenwith SCT, with 44% of the children having socialemotional vulnerabilities in the borderlineor extremely low range, compared to typicallydeveloping children. In this cohort, no sig-nificant predictive effects of karyotype-subtype (XXX, XXY, XYY) were found. Alreadyfrom a very early age, SCT can be associated with increased risk for vulnerabilities in adap-tive social functioning. These findings suggest that SCT impact the maturation of the socialbrain already from an early age, and stress the importance of early monitoring and (pre-ventive) support early social development in young children with SCT.Development Psychopathology in context: clinical setting

Early social behavior in young children with sex chromosome trisomies (XXX, XXY, XYY): profiles of observed social interactions and social impairments associated with autism spectrum disorder (ASD)

Individuals with Sex Chromosome Trisomies (SCT; XXX, XXY, XYY) have an increased vulnerability for developing challenges in social adaptive functioning. The present study investigates social interaction behavior in the context of varying social load, and Autism Spectrum Disorder (ASD) symptomatology in young children aged 1–7.5 years old, with SCT (N=105) and control children (N=101). Children with SCT show less interaction behaviors and more social withdrawal, as compared to their control peers, which were most evident in the high social load condition. Second, social impairments related to ASD are more prevalent, as compared to controls (27.1% at clinical level). These fndings stress the importance of early monitoring and (preventive) support of early social development in young children with SCT.Development Psychopathology in context: clinical setting

The impact of sex chromosome trisomies (XXX, XXY, XYY) on gaze towards faces and afect recognition: a cross-sectional eye tracking study

Background: About 1:650–1000 children are born with an extra X or Y chromosome (47,XXX; 47,XXY; 47,XYY), which results in a sex chromosome trisomy (SCT). This international cross-sectional study was designed to investigate gaze towards faces and afect recognition during early life of children with SCT, with the aim to fnd indicators for support and treatment. Methods: A group of 101 children with SCT (aged 1–7 years old; Mage= 3.7 years) was included in this study, as well as a population-based sample of 98 children without SCT (Mage= 3.7). Eye gaze patterns to faces were measured using an eye tracking method that quantifes frst fxations and fxation durations on eyes of static faces and fxation durations on eyes and faces in a dynamic paradigm (with two conditions: single face and multiple faces). Affect recognition was measured using the subtest Affect Recognition of the NEPSY-II neuropsychological test battery. Recruitment and assessment took place in the Netherlands and the USA. Results: Eye tracking results reveal that children with SCT show lower proportion fxation duration on faces already from the age of 3 years, compared to children without SCT. Also, impairments in the clinical range for afect recognition were found (32.2% of the SCT group scored in the well below average range). Conclusions: These results highlight the importance to further explore the development of social cognitive skills of children with SCT in a longitudinal design, the monitoring of afect recognition skills, and the implementation of (preventive) interventions aiming to support the development of attention to social important information and afect recognition.Development Psychopathology in context: clinical setting

Mindfulness in detentie: Plan- en Procesevaluatie. Eindrapport

Rapport in opdracht van het Wetenschappelijk Onderzoek en Documentatiecentrum (WODC)Development Psychopathology in context: clinical setting

Early symptoms of autism spectrum disorder (ASD) in 1–8 year old children with sex chromosome trisomies (XXX, XXY, XYY), and the predictive value of joint attention

The objective of the present study is to investigate the impact of Sex Chromosome Trisomy (SCT; XXX, XXY, XYY) on the early appearance of Autism Spectrum Disorder (ASD) symptoms, and the predictive value of Joint Attention for symptoms of ASD. SCTs are specifc genetic conditions that may serve as naturalistic ‘at risk’ models of neurodevelopment, as they are associated with increased risk for neurobehavioral vulnerabilities. A group of 82 children with SCT (aged 1–8 years) was included at baseline of this longitudinal study. Joint Attention was measured at baseline with structured behavior observations according to the Early Social Communication Scales. ASD symptoms were assessed with the Modifed Checklist for Autism in Toddlers questionnaire and Autism Diagnostic Interview-Revised in a 1-year follow-up. Recruitment and assessment took place in the Netherlands and in the United States. The results demonstrate that ASD symptoms were substantially higher in children with SCT compared to the general population, with 22% of our cohort at clinical risk for ASD, especially in the domain of social interaction and communication. Second, a predictive value of Joint Attention was found for ASD symptoms at 1-year follow-up. In this cohort, no diferences were found between karyotype-subtypes. In conclusion, from a very early age, SCT can be associated with an increased risk for vulnerabilities in adaptive social functioning. These fndings show a neurodevelopmental impact of the extra X or Y chromosome on social adaptive development associated with risk for ASD already from early childhood onward. These fndings advocate for close monitoring and early (preventive) support, aimed to optimize social development of young children with SCT.Development Psychopathology in context: clinical setting

Immunocompromised patients with acute respiratory distress syndrome : Secondary analysis of the LUNG SAFE database

The aim of this study was to describe data on epidemiology, ventilatory management, and outcome of acute respiratory distress syndrome (ARDS) in immunocompromised patients. Methods: We performed a post hoc analysis on the cohort of immunocompromised patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) study. The LUNG SAFE study was an international, prospective study including hypoxemic patients in 459 ICUs from 50 countries across 5 continents. Results: Of 2813 patients with ARDS, 584 (20.8%) were immunocompromised, 38.9% of whom had an unspecified cause. Pneumonia, nonpulmonary sepsis, and noncardiogenic shock were their most common risk factors for ARDS. Hospital mortality was higher in immunocompromised than in immunocompetent patients (52.4% vs 36.2%; p < 0.0001), despite similar severity of ARDS. Decisions regarding limiting life-sustaining measures were significantly more frequent in immunocompromised patients (27.1% vs 18.6%; p < 0.0001). Use of noninvasive ventilation (NIV) as first-line treatment was higher in immunocompromised patients (20.9% vs 15.9%; p = 0.0048), and immunodeficiency remained independently associated with the use of NIV after adjustment for confounders. Forty-eight percent of the patients treated with NIV were intubated, and their mortality was not different from that of the patients invasively ventilated ab initio. Conclusions: Immunosuppression is frequent in patients with ARDS, and infections are the main risk factors for ARDS in these immunocompromised patients. Their management differs from that of immunocompetent patients, particularly the greater use of NIV as first-line ventilation strategy. Compared with immunocompetent subjects, they have higher mortality regardless of ARDS severity as well as a higher frequency of limitation of life-sustaining measures. Nonetheless, nearly half of these patients survive to hospital discharge. Trial registration: ClinicalTrials.gov, NCT02010073. Registered on 12 December 2013

Resolved versus confirmed ARDS after 24&#160;h: insights from the LUNG SAFE study

Purpose: To evaluate patients with resolved versus confirmed ARDS, identify subgroups with substantial mortality risk, and to determine the utility of day 2 ARDS reclassification. Methods: Our primary objective, in this secondary LUNG SAFE analysis, was to compare outcome in patients with resolved versus confirmed ARDS after 24\ua0h. Secondary objectives included identifying factors associated with ARDS persistence and mortality, and the utility of day 2 ARDS reclassification. Results: Of 2377 patients fulfilling the ARDS definition on the first day of ARDS (day 1) and receiving invasive mechanical ventilation, 503 (24%) no longer fulfilled the ARDS definition the next day, 52% of whom initially had moderate or severe ARDS. Higher tidal volume on day 1 of ARDS was associated with confirmed ARDS [OR 1.07 (CI 1.01\u20131.13), P = 0.035]. Hospital mortality was 38% overall, ranging from 31% in resolved ARDS to 41% in confirmed ARDS, and 57% in confirmed severe ARDS at day 2. In both\ua0resolved and confirmed\ua0ARDS, age, non-respiratory SOFA score, lower PEEP and P/F ratio, higher peak pressure and respiratory rate were each\ua0associated with mortality. In confirmed ARDS, pH and the presence of immunosuppression or neoplasm were also associated\ua0with mortality. The increase in area under the receiver operating curve for ARDS reclassification on day 2 was marginal. Conclusions: ARDS, whether resolved or confirmed at day 2, has a high mortality rate. ARDS reclassification at day 2 has limited predictive value for mortality. The substantial mortality risk in severe confirmed ARDS suggests that complex interventions might best be tested in this population. Trial Registration: ClinicalTrials.gov NCT02010073. \ua9 2018, Springer-Verlag GmbH Germany, part of Springer Nature and ESICM