Research on SCT at Leiden University: Cohorts: Personal roadmap: Mix of prenatal follow-up and referred cases. Sophie van Rijn
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1 The cognitive and behavioral profile of 47,XXX (Trisomy X): a research approach Founded in 1575 Sophie van Rijn Associate professor Leiden University, The Netherlands Faculty of Social and Behavioural Sciences Department of Clinical Child and Adolescent Studies Prof. Hanna Swaab, PhD Sophie van Rijn, PhD SCT Research group Leo de Sonneville, PhD Marcia Brandenburg-Goddard Marit Bierman Petra Barneveld, PhD Personal roadmap: Research on SCT at Leiden University: MSc in Neuropsychology (University of Amsterdam) PhD in Psychology and Psychiatry (Utrecht University, University Medical Center Utrecht) Activities: teaching, research Collaboration with outpatient clinic Leiden University Cohorts: 58 adults with XXY ( ) 56 boys with XXY ( ) 60 boys and girls with an extra X ( ) Mix of prenatal follow-up and referred cases 1
2 Considerations when doing research Extra X 75 % of the research is focused on physical and medical issues Research aims: Identify strenghts and difficulties in psychological development Understand the underlying mechanisms of psychological development: why do children develop emotional or behavioral difficulties? How representative is the group of girls with 47,XXX participating in research? Diagnosed because of prenatal screening or developmental problems? About 1 in 1000 girls have 47,XXX: why do many girls remain undiagnosed (about 90%)? No clinical care needed? Clinical care may be needed, but is not found/provided Clinical care is provided, but without knowledge of the underlying genetic condition and how does this affect what we know about developmental risks? Which characteristics of the child are determined by the extra X and which are the effect of the other 46 chromosomes? Your genetic make-up is not the only determinant of development: environmental factors such as parenting, education, life experiences also shape development! Research is always about groups What do we know about developmental risks in Trisomy X? Newborn screening SCT studies (USA, Canada, UK) Small groups of girls with Trisomy X follow-up from birth through adulthood Variation in outcome (not unique to Trisomy X) Compromised motor development: fine/gross motor skills, coordination Delayed language development Difficulties in language understanding, language production and speech (40-90 % speech therapy) IQ on average around Risk for learning problems: reading and arithmetics Social immaturity, compromised social adjustment, social and emotional withdrawal Anxious, risk for depressive symptoms, ADHD symptoms (25%) (Reviewed by Legget et al 2010 and Tartaglia et al 2010) 30 girls with Trisomy X Oxford SCT study (Bishop 2010) Social functioning Girls were described by their parents as: - Caring - Withdrawn or shy - Artistic: drawing, handicrafts - Sometimes somewhat naïve, stubborn or vulnerable Vulnerable in areas of: - Learning in school - Communication: (finding words, understanding complex messages, reading between the lines) - Emotional outbursts (frustration) - Motoric clumsiness - Social interactions; friends, school, jobs Functioning in society = Social adaptation to others Relationships/family Friendships School/education Jobs 2
3 Social behavior Cooperate/collaborate Share Solve conflicts Give comfort Make friends Deal with your own emotions Pay attention to emotions, wishes and desires of others Understand the consequences of your behavior (IN)ABILITY to navigate socially NEED to have fulfilling social interactions Social ability is a good indicator of a person s resilience and capacity to meet the demands of society Social skills Processing is done in the brain SEE: LABEL: pay attention to social cues of others understand the meaning of social cues INPUT OUTPUT RESPOND: appropriate reaction to social cues Incoming information Oversee Response Complex behavior: Socially adapt right here right now A lot of incoming information Concentrate Filter Categorize Label Cues can be very subtle Memorize Switch & adjust Social ability has to do with the processing of information Monitor & control (emotions, thoughts, behavior) Empathize Processing is done in the brain Brain-behavior framework INPUT OUTPUT Emotional/behavioral problems environment Cognitive functions environment Brain architecture environment Genetic make-up environment 3
4 Brain development is dynamic: windows of opportunity for stimulation, training and intervention Higher cognitive functions show prolonged development (Adapted from McCalla, Rainbow Rehabilitation Centers ) (Adapted from McCalla, Rainbow Rehabilitation Centers ) Identifying targets for stimulation, training and intervention: the importance of studying brain-behavior pathways Boys (XXY) versus girls (XXX): (Adapted from Legget et al 2010) Boys (XXY) versus girls (XXX) -behavioral data- Boys (XXY) versus girls (XXX) -cognitive data- Intellectual functioning (Van Rijn et al. J.Aut. Dev. Dis. 2014) 4
5 Boys (XXY) versus girls (XXX) -cognitive data- Boys (XXY) versus girls (XXX) -cognitive data- Language Higher order cognitive functions Boys (XXY) versus girls (XXX) -cognitive data- Boys (XXY) versus girls (XXX) Understanding social information Identifying vulnerable children IQ scores Clinically impaired Normal range Talented Control group Boys and girls with extra X 5
6 What children think themselves % children with an extra X who worry about: Social skills Physical abilities Intellectual abilities Appearance Children with an extra X feel more competent than control group 87.5% of the children with significant behavioral problems according to parents, do not report a problem with competence themselves How children deal with negative life events Similar to other children, children with an extra X apply coping strategies to regulate their emotions: Accept Concentrate on positive things Concentrate on planning what to do Re-evaluate in a more positive way Children with an extra X (both boys and girls) are significantly more inclined to: Ruminate: 19.5 % moderately/excessively The tendency for thoughts and emotions to get stuck, to repetitively overthink one s distress, rather than focussing on solutions External blame: 25.9 % moderately/excessively Identify the cause of one s distress in external factors, for example to hold others responsible for your own distress (Bierman et al. submitted) Boys and girls with an extra X 9-18 years Significantly elevated scores (similar for boys and girls): Comparing the profile to ASD: symptoms at age 4-5 (Van Rijn et al. J.Aut. Dev. Dis. 2014) Children with an extra X (34 boys and 26 girls) Average Mild Severe (T<65) (65<T<70) (T>70) 43.4 % 20.8 % 35.8 % CBCL Total score Social problems 58.5 % 24.5 % 17.0 % Attention problems 71.7 % 9.4 % 18.9 % Thought problems 62.3 % 22.6 % 15.1 % Anxious -depressed 71.7 % 15.1 % 13.2 % Withdrawal 62.3 % 22.6 % 15.1 % Somatic complaints 73.6 % 9.4 % 17.0 % Aggressive behavior 84.9 % 11.3 % 3.8 % Rule breaking behavior 88.7 % 9.4 % 1.9 % Vulnerablity for clinical diagnosis: Girls: Bishop et al: 0 % has ASD Boys: Tartaglia et al: 5 % has ASD Bishop et al: 11 % has ASD Cederlof et al: 3 % has ASD Bruining et al.: 27 % has ASD A dimensional approach A dimensional approach con Vulnerablity for autism symptoms in children with an extra X Our data: 25 % in severe range Boys: Tartaglia et al: 25% mild to severe range Comparison to ASD: milder symptoms X ASD Also elevated in children without a history of typical autism symptoms: Distribution of autism traits in the general population (Van Rijn et al. J.Aut. Dev. Dis. 2014) 6
7 Other differences between children with an extra X chromosome and children with ASD Why emotional or behavioral problems occur in children with XXX and XXY Children with an extra X have more social anxiety than children with ASD: - More concern about social relations - More reflection on social situations Daily life attention-executive skills Attention-executive Executive functions are higher order cognitive functions essential for regulating and managing thought, emotion and behavior Communication Conveying meaning and messages through symbols using: verbal cues (language) non-verbal cues (gestures, intonation, body posture, eye contact) Socio-emotional Perception and processing of socio-emotional cues, beginning with basic aspects of face and emotion perception and extending to complex cognitive processes involving understanding emotions, desires and mental states of others % has score in normal range 28.9 % has score in clinical range (significantly elevated, similar for boys and girls) Inhibition: Ability to control impulses and to stop engaging in a behavior. Shifting: Ability to move freely from one activity or situation to another; to tolerate change; to switch or alternate attention. Emotional Control: Ability to regulate emotional responses appropriately. Initiate: Ability to begin an activity and to independently generate ideas or problem-solving strategies. Working memory: Ability to hold information when completing a task, when encoding information, or when generating goals/plans in a sequential manner. Plan/organize: Ability to anticipate future events; to set goals; to develop steps; to grasp main ideas; to organize and understand the main points in written or verbal presentations. Organization of materials: Ability to put order in work, play, and storage spaces (e.g., desks, lockers, backpacks, and bedrooms). Monitor: Ability to check work and to assess one s own performance; ability to keep track of the effect of one s own behavior on other people. (Van Rijn et al. GBB, in press) - Stable concentration for longer periods of time - Focus on what s important, ignore irrelevant things (that you can see, hear, think, feel) 71.7 % has score in the normal range 28.3 % has score in the clinical range (significantly elevated) Concentration and attention - The break on behavior, thoughts and emotions - Ability to control impulses (inhibitory control) and to stop engaging in a behavior % has score in normal range 23.7 % has score in clinical range (significantly elevated) Inhibition Children with more inhibition problems have reduced control over their behavior (aggressive behavior) and thought (derailment). Inhibitiory control is impacted by early life stress (in prep) (Van Rijn et al. GBB, in press) (Van Rijn et al. GBB, in press) 7
8 Mental flexibility Working memory Ability to move freely from one activity or situation to another To tolerate change To switch or alternate attention To use new information to change plans 62.2 % has score in normal range 37.8 % has score in clinical range (significantly elevated) ability to hold information when completing a task when encoding information or when generating goals/plans in a sequential manner 81.1 % has score in normal range 18.9 % has score in clinical range (significantly elevated) Children with more mental flexibility problems have more autism symptoms (van Rijn et al. J.Psych.Res. 2012) Mental flexibility is impacted by early life stress (in prep) (Van Rijn et al. GBB, in press) (Van Rijn et al. GBB, in press) Getting the big picture Oversee situations Visual integration Language Understanding verbal messages Expressing your thoughts Use language in a socially appropriate way 70 % has score in normal range 30 % has score in clinical range (significantly elevated) Children succeed, but it takes more time Significantly more language problems: - Similar for boys and girls - Level of language skills is related to vulnerability for autism symptoms (Van Rijn et al Act Ped 2011) Domain: Normal range Significantly more problems with language coherence and logic: (Bierman et al. submitted) 60 % score in normal range 40 % score in clinical range Clinical range Language Production 59.6 % 40.4 % Language Understanding 61.0 % 39.0 % Social use of language 72.2 % 27.8 % - Reduced coherence is related to attention-executive difficulties (Van Rijn et al. in preparation) Social cognition Predictors of social cognition (perspective taking) in ASD versus extra X Take the perspective of another person Understand that other persons may have different thoughts, feelings, wishes and desires than you Empathize with others, share emotions ASD: language skills, face processing Extra X: attention-executive skills 48.2 % has score in normal range 51.8 % has score in clinical range (significantly elevated) Social cognition is disproportionally impacted by early life stress (in prep) Other pathways other ways of stimulation, training or intervention? (Van Rijn et al. GBB 2014) (Van Rijn et al. GBB 2014) 8
9 Thus.. Thus.. INPUT OUTPUT INPUT OUTPUT Incoming information? Social problems Incoming information Social cognition Language Attention-executive Social problems Developmental vulnerabilities in girls with Trisomy X: Social interactions may be challenging A preference for doing things in a particular way and order Attention to details rather than the big picture Difficulty with expressing thoughts and emotions Difficult to see things from other people s perspective Anxious and/or withdrawn in social situations, difficulties in managing friendships Difficulties with controlling thoughts, behavior, emotions (disorganized, impulsive, emotional outbursts) Easily distracted, making plans or organizing things may be a challenge Lessons we have learned so far Neuropsychological assessments is necessary to: answer the question why children develop emotional or behavioral problems identify vulnerabillity markers (children who may be in need of monitoring) identify targets for treatment We need to plan systematic research studies focusing on the effectiveness of training and support for girls and women with Trisomy X The cognitive and behavioral profile may be very similar in boys and girls with an extra X, although we need larger studies We need to share scientific knowledge with (upcoming) professionals in the field of mental health care as much as possible We need to collaborate internationally to join forces During conversation, children may have difficulties taking turns, staying on-topic, or understand complex messages Nicole Tartaglia Denver, USA Carole Samango-Sprouse Washington, USA A focus on emotions NEW RESEARCH AIMS Trisomy X Emotion are very important for social adaptation: - motivate to act - guide the selection of responses ( gut feeling / intuition) - empathize with others - understand others Emotions: physiological response, feeling, thoughts, behavior Physiological response is automatic and often subtle: changes in heart rate changes in sweat production Important indicators of emotional reactivity 9
10 Social cues elicit emotions How do we measure this? Automatic social orienting towards faces Eye contact leads to affective arousal (physiological response) Looking towards and away from eyes helps to regulate one s own arousal levels Eye tracker Skin conductance recording Understanding and labeling emotions Patterns of fixating on eyes of others Looking Feeling Understanding (Van Rijn et al. PloS One in press) Video clips Adults with XXY anxiety sadness feeling pain happiness Fits with earlier findings: - More influenced by emotions according to parental report - More influenced by emotions in decision making (Van Rijn 2006) - High levels of arousal during social interaction (Van Rijn 2006) Adults with XXY Adults with XXY understanding looking 10
11 Social orienting towards faces no XXY XXY Weak social orienting Independent of expression type Independent of expression intensity (Van Rijn et al. JINS in press) Emotion-disregulation-hypothesis : Also for Trisomy X? eyecontact difficulties interpreting social message increased affective arousal (psychophysiological responses) avoidance of eyes inefficient in reducing arousal anxiety remains high: avoidance of social interactions reduced social learning experiences Do we also see this in Trisomy X? Do we see this already very early in development? How important is this for the development of language and communication? Can we stimulate social orienting? How do we support children and adults with problems in these areas? Collecting research data is important! Thank you for your attention! 11
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