Internalising and Externalising Symptoms and Their Association with the Family Environment in Young Children with Williams Syndrome: A Longitudinal Study.

Williams Syndrome (WS) involves high rates of psychopathology across the lifespan. However, little is known about the early, longitudinal trajectory of internalising/externalising symptoms or the association between these and the family environment in WS. WS (n = 16; aged 2 years, 2 months to 9 years, 5 months) and typically developing or TD (n = 46; aged 2 years, 2 months to 11 years, 1 month) children were assessed on two occasions over 2.5 years utilising parent report questionnaires-the Child Behaviour Checklist and the Family Environment Scale. No statistically significant changes were found in CBCL/psychopathology profiles across timepoints, on average, for either WS or TD children. However, reliable change scores showed WS children had considerable variability in CBCL scores over time. Cross-sectionally, the WS group showed higher scores (reflecting more psychopathology) compared to TD controls at both time points across most CBCL subscales, with elevated overall psychopathology problems identified in 56-68% of WS children (versus 8% in TD controls). Psychopathology was not associated with sex, chronological age, or cognitive ability in WS. Conflict in the family environment was positively associated with higher Attention Problems at Time 1 in the WS group, whilst the TD group showed associations between family conflict and total psychopathology problems at both time points and between family cohesion and total psychopathology problems at Time 2. Family environment did not differ between groups, except for lower engagement in intellectual and cultural activities in WS. Findings highlight variable Internalising and Externalising Problems in young WS children over time, with greater biological than environmental contributions to psychopathology in WS.

Psychometric properties of the Self-Beliefs related to Social Anxiety (SBSA) scale in a sample of individuals with social anxiety disorder.

The Self-Beliefs related to Social Anxiety (SBSA) scale assesses maladaptive social-evaluative beliefs, a key aspect in models of social anxiety disorder (SAD) that is frequently measured in research and clinical contexts. The SBSA has been evaluated psychometrically in student samples, but not in a large sample of individuals diagnosed with SAD. The current study tested the psychometric properties of the SBSA in a sample of individuals with SAD pooled from several studies (total N = 284). Results showed that the optimal factor structure for the SBSA was a correlated three-factor model (high standard beliefs factor, conditional beliefs factor, unconditional beliefs factor). The SBSA total and its subscales (formed based on the factors) exhibited good internal consistency. In terms of construct validity, the SBSA total, the high standard beliefs subscale, and conditional beliefs subscale had stronger associations with a measure of social anxiety than with a measure of depression, although the unconditional beliefs subscale was similarly related to both measures of social anxiety and depression. In terms of discriminative validity, the sample of individuals with SAD had higher SBSA total and subscale scores compared with a sample of individuals without SAD (N = 32). These findings provide a psychometric evidence base justifying the use of the SBSA for the assessment of maladaptive social-evaluative beliefs.

Extending the positive bias in Williams syndrome: The influence of biographical information on attention allocation.

There is evidence that individuals with Williams syndrome (WS) show an attention bias toward positive social-perceptual (happy) faces. Research has not yet considered whether this attention bias extends beyond social-perceptual stimuli to perceptually neutral stimuli that are paired with positive (trustworthy) biographical information. Fourteen participants with WS (mean age = 21 years, 1 month) learned to associate perceptually neutral faces with trustworthy (positive), neutral, or untrustworthy (negative) biographical information, before completing a dot-probe task where the same biographical faces were presented. The performance of the WS group was compared to two typically developing control groups, individually matched to the WS individuals on chronological age and mental age, respectively. No between-group bias toward untrustworthy characters was observed. The WS group displayed a selective attention bias toward trustworthy characters compared to both control groups (who did not show such a bias). Results support previous findings that indicate WS individuals show a preference for positive social-perceptual stimuli (happy faces) at the neurological, physiological, and attentional levels. The current findings extend this work to include a "top-down" positive bias. The implications of a positive bias that extends beyond social-perceptual stimuli (or "bottom-up" processes) in this syndrome are discussed.

Attention to faces in social context in children with neurofibromatosis type 1.

AIM: To examine visual attention to faces within social scenes in children with neurofibromatosis type 1 (NF1) and typically developing peers. METHOD: Using eye-tracking technology we investigated the time taken to fixate on a face and the percentage of time spent attending to faces relative to the rest of the screen within social scenes in 24 children with NF1 (17 females, seven males; mean age 10y 4mo [SD 1y 9mo]). Results were compared with those of 24 age-matched typically developing controls (11 females, 13 males; mean age 10y 3mo [SD 2y]). RESULTS: There was no significant between-group differences in time taken to initially fixate on a face (p=0.617); however, children with NF1 spent less time attending to faces within scenes than controls (p=0.048). Decreased attention to faces was associated with elevated autism traits in children with NF1. INTERPRETATION: Children with NF1 spend less time attending to faces than typically developing children when presented in social scenes. Our findings contribute to a growing body of literature suggesting that abnormal face processing is a key aspect of the social-cognitive phenotype of NF1 and appears to be related to autism spectrum disorder traits. Clinicians should consider the impact of reduced attention to faces when designing and implementing treatment programmes for social dysfunction in this population. WHAT THIS PAPER ADDS: Children with neurofibromatosis type 1 (NF1) demonstrated atypical gaze behaviour when attending to faces. NF1 gaze behaviour was characterized by normal initial fixation on faces but shorter face dwell time. Decreased attention to faces was associated with elevated autism traits in the sample with NF1.

Atypical Local Interference Affects Global Processing in Children with Neurofibromatosis Type 1.

OBJECTIVES: To examine hierarchical visuospatial processing in children with neurofibromatosis type 1 (NF1), a single gene disorder associated with visuospatial impairments, attention deficits, and executive dysfunction. METHODS: We used a modified Navon paradigm consisting of a large "global" shape composed of smaller "local" shapes that were either congruent (same) or incongruent (different) to the global shape. Participants were instructed to name either the global or local shape within a block. Reaction times, interference ratios, and error rates of children with NF1 (n=30) and typically developing controls (n=24) were compared. RESULTS: Typically developing participants demonstrated the expected global processing bias evidenced by a vulnerability to global interference when naming local stimuli without a cost of congruence when naming global stimuli. NF1 participants, however, experienced significant interference from the unattended level when naming both local and global levels of the stimuli. CONCLUSIONS: Findings suggest that children with NF1 do not demonstrate the typical human bias of processing visual information from a global perspective. (JINS, 2017, 23, 446-450).

Facial emotion recognition, face scan paths, and face perception in children with neurofibromatosis type 1.

OBJECTIVE: This study aimed to investigate face scan paths and face perception abilities in children with Neurofibromatosis Type 1 (NF1) and how these might relate to emotion recognition abilities in this population. METHOD: The authors investigated facial emotion recognition, face scan paths, and face perception in 29 children with NF1 compared to 29 chronological age-matched typically developing controls. Correlations between facial emotion recognition, face scan paths, and face perception in children with NF1 were examined. RESULTS: Children with NF1 displayed significantly poorer recognition of fearful expressions compared to controls, as well as a nonsignificant trend toward poorer recognition of anger. Although there was no significant difference between groups in time spent viewing individual core facial features (eyes, nose, mouth, and nonfeature regions), children with NF1 spent significantly less time than controls viewing the face as a whole. Children with NF1 also displayed significantly poorer face perception abilities than typically developing controls. Facial emotion recognition deficits were not significantly associated with aberrant face scan paths or face perception abilities in the NF1 group. CONCLUSIONS: These results suggest that impairments in the perception, identification, and interpretation of information from faces are important aspects of the social-cognitive phenotype of NF1. (PsycINFO Database Record

Characterising the Profile of Everyday Executive Functioning and Relation to IQ in Adults with Williams Syndrome: Is the BRIEF Adult Version a Valid Rating Scale?

Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included: The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition-Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS.

A meta-analysis of neuropsychological functioning in first-episode bipolar disorders.

Broad neuropsychological deficits have been consistently demonstrated in well-established bipolar disorder. The aim of the current study was to systematically review neuropsychological studies in first-episode bipolar disorders to determine the breadth, extent and predictors of cognitive dysfunction at this early stage of illness through meta-analytic procedures. Electronic databases were searched for studies published between January 1980 and December 2013. Twelve studies met eligibility criteria (N = 341, mean age = 28.2 years), and pooled effect sizes (ES) were calculated across eight cognitive domains. Moderator analyses were conducted to identify predictors of between-study heterogeneity. Controlling for known confounds, medium to large deficits (ES ≥ 0.5) in psychomotor speed, attention and working memory, and cognitive flexibility were identified, whereas smaller deficits (ES 0.20-0.49) were found in the domains of verbal learning and memory, attentional switching, and verbal fluency. A medium to large deficit in response inhibition was only detected in non-euthymic cases. Visual learning and memory functioning was not significantly worse in cases compared with controls. Overall, first-episode bipolar disorders are associated with widespread cognitive dysfunction. Since euthymia was not associated with superior cognitive performance in most domains, these results indicate that even in the earliest stages of disease, cognitive deficits are not mood-state dependent. The current findings have important implications for whether cognitive impairments represent neurodevelopmental or neurodegenerative processes. Future studies need to more clearly characterise the presence of psychotic features, and the nature and number of previous mood episodes.

Social approach and emotion recognition in fragile X syndrome.

Evidence is emerging that individuals with Fragile X syndrome (FXS) display emotion recognition deficits, which may contribute to their significant social difficulties. The current study investigated the emotion recognition abilities, and social approachability judgments, of FXS individuals when processing emotional stimuli. Relative to chronological age- (CA-) and mental age- (MA-) matched controls, the FXS group performed significantly more poorly on the emotion recognition tasks, and displayed a bias towards detecting negative emotions. Moreover, after controlling for emotion recognition deficits, the FXS group displayed significantly reduced ratings of social approachability. These findings suggest that a social anxiety pattern, rather than poor socioemotional processing, may best explain the social avoidance observed in FXS.

Gait profiles as indicators of domain-specific impairments in executive control across neurodevelopmental disorders.

In neurodevelopmental disorders, unique profiles of executive control and attention appear to co-occur with poor motor coordination. However, less is known about how syndrome-specific cognitive profiles interact with motor control and impact behavioural outcomes in neurodevelopmental disorders such as Williams syndrome (WS) and Down syndrome (DS). Here we aimed to examine the extent to which specific components of executive function interact with gait control when performing cognitive dual-tasks (verbal fluency, digit span) in WS and DS. Spatiotemporal gait characteristics and intra-individual variability of gait were assessed in individuals with WS who were matched on spatial ability to individuals with DS, and chronologically age (CA) matched controls. During the concurrent verbal fluency task, the WS group had greater dual-task costs on spatiotemporal gait parameters and variability than CA controls. Conversely, individuals with DS had selective gait interference during the concurrent digit span task when compared to CA controls, but only under increased demands on cognitive control where there was greater variability in step timing in DS. The interrelationships between cognitive-motor interference and behavioural measures of executive functioning appeared to differentiate between WS and DS, and emphasise the importance of task modality in unpacking the executive control profile in these neurodevelopmental disorders. These findings support the notion that associated cerebellar-cortico abnormalities may produce quite distinct profiles of executive control across cognitive and motor domains that impact on behavioural outcomes in neurodevelopmental disorders.

The interplay between executive control and motor functioning in Williams syndrome.

Previous studies suggest that individuals with Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, show specific weaknesses in visual attention and response inhibition within the visuospatial domain. Here we examine the extent to which impairments in attentional control extend to the visuomotor domain using a well-validated measure of choice stepping reaction time (CSRT) in individuals with WS. We examined the interaction between executive control and visually guided stepping using a verbal fluency dual-task or Go/NoGo paradigm during CSRT performance. Relationships between dual-task and inhibitory stepping and behavioural inattention and hyperactivity were also examined. Our results showed clear dual-task costs in stepping response times when performing a concurrent cognitive task in the WS group when compared to spatial and verbal ability matched typically developing controls. Although no group differences in stepping accuracy were observed between the WS and typically developing control groups, the WS group showed progressive slowing and more variable response times across the duration of the Go/NoGo task. These results suggest dysfunction in circuits involved in top-down attentional control processes in WS. These findings provide novel evidence that core executive control deficits in WS extend to the visuomotor domain, and impact on ADHD-related inattentive symptoms.

Neuropsychological and socio-occupational functioning in young psychiatric outpatients: a longitudinal investigation.

BACKGROUND: Clinical symptoms and neuropsychological deficits are longitudinally associated with functional outcome in chronic psychiatric cohorts. The current study extended these findings to young and early-course psychiatric outpatients, with the aim of identifying cognitive markers that predict later socio-occupational functioning. METHODS: At baseline, 183 young psychiatric outpatients were assessed. Ninety-three returned for follow-up (M = 21.6 years old; SD = 4.5) with an average re-assessment interval of 21.6 months (SD = 7.0), and primary diagnoses of major depressive disorder (n = 34), bipolar disorder (n = 29), or psychosis (n = 30). The primary outcome measure was cross-validated with various other functional measures and structural equation modelling was used to map out the interrelationships between predictors and later functional outcome. RESULTS: Good socio-occupational functioning at follow-up was associated with better quality of life, less disability, current employment and being in a romantic relationship. The final structural equation model explained 47.5% of the variability in functional outcome at follow-up, with baseline neuropsychological functioning (a composite of memory, working memory and attentional switching) the best independent predictor of later functional outcome. Notably, depressive and negative symptoms were only associated with functioning cross-sectionally. Diagnosis at follow-up was not associated with functional outcome. CONCLUSIONS: Neuropsychological functioning was the single best predictor of later socio-occupational outcome among young psychiatric outpatients. Therefore, framing psychiatric disorders along a neuropsychological continuum is likely to be more useful in predicting functional trajectory than traditional symptom-based classification systems. The current findings also have implications for early intervention utilising cognitive remediation approaches.

Attribution of negative intention in Williams syndrome.

People with Williams syndrome (WS) are said to have sociable and extremely trusting personalities, approaching strangers without hesitation. This study investigated whether people with WS are less likely than controls to attribute negative intent to others when interpreting a series of ambiguous pictures. This may, at least partially, explain their hypersociability toward strangers. Twenty-seven individuals with WS and 54 typically developing controls (27 matched to WS participants on sex and chronological age and 27 matched on sex and mental age) viewed 10 ambiguous pictures, where one person in the picture may be seen as having a negative objective. Participants were asked to describe what was happening in the picture. Responses were scored for negative intention attribution (NIA). NIA was reduced in WS individuals relative to typically developing controls of the same chronological age, but was similar to typically developing controls of the same mental age. Findings are discussed in relation to possible underlying neurological and cognitive mechanisms and practical implications for understanding and teaching stranger danger to people with WS.

Hyper-reactivity in fragile X syndrome females: generalised or specific to socially-salient stimuli? A skin conductance study.

Fragile X syndrome (FXS) is characterised by hyper-reactivity, autistic tendencies and social anxiety. It has been hypothesised that the FXS social phenotype is secondary to a generalised hyper-reactivity that leads to social avoidance. No study, however, has investigated whether hyperarousal in FXS is generalised or more specific to socially salient information. We recorded skin conductance responses (SCRs) while females with FXS, as well as chronological age-(CA-) and mental age-(MA-) matched controls, viewed two sets of visual images: direct-gaze emotional faces and affectively arousing scenes. Explicit emotion recognition and subjective ratings of emotions aroused by images were also recorded. Overall, females with FXS displayed hyper-reactivity only when viewing the more socially salient stimuli (emotional faces), compared to CA-matched controls, but not MA-matched controls. Moreover, females with FXS also displayed atypical emotion recognition abilities and subjective ratings of their own emotional states. These findings suggest that any hyper-reactivity observed in FXS may be more specific to socially salient stimuli, rather than generalised.

Viewing social scenes: a visual scan-path study comparing fragile X syndrome and Williams syndrome.

Fragile X syndrome (FXS) and Williams syndrome (WS) are both genetic disorders which present with similar cognitive-behavioral problems, but distinct social phenotypes. Despite these social differences both syndromes display poor social relations which may result from abnormal social processing. This study aimed to manipulate the location of socially salient information within scenes to investigate the visual attentional mechanisms of: capture, disengagement, and/or general engagement. Findings revealed that individuals with FXS avoid social information presented centrally, at least initially. The WS findings, on the other hand, provided some evidence that difficulties with attentional disengagement, rather than attentional capture, may play a role in the WS social phenotype. These findings are discussed in relation to the distinct social phenotypes of these two disorders.

Emotion recognition and visual-scan paths in Fragile X syndrome.

This study investigated emotion recognition abilities and visual scanning of emotional faces in 16 Fragile X syndrome (FXS) individuals compared to 16 chronological-age and 16 mental-age matched controls. The relationships between emotion recognition, visual scan-paths and symptoms of social anxiety, schizotypy and autism were also explored. Results indicated that, compared to both control groups, the FXS group displayed specific emotion recognition deficits for angry and neutral (but not happy or fearful) facial expressions. Despite these evident emotion recognition deficits, the visual scanning of emotional faces was found to be at developmentally appropriate levels in the FXS group. Significant relationships were also observed between visual scan-paths, emotion recognition performance and symptomology in the FXS group.

A role for transcription factor GTF2IRD2 in executive function in Williams-Beuren syndrome.

Executive functions are amongst the most heritable cognitive traits with twin studies indicating a strong genetic origin. However genes associated with this domain are unknown. Our research into the neurodevelopmental disorder Williams-Beuren syndrome (WBS) has identified a gene within the causative recurrent 1.5/1.6 Mb heterozygous microdeletion on chromosome 7q11.23, which may be involved in executive functioning. Comparative genome array screening of 55 WBS patients revealed a larger ∼1.8 Mb microdeletion in 18% of cases, which results in the loss of an additional gene, the transcription factor GTF2IRD2. The GTF gene family of transcription factors (GTF2I, GTF2IRD1 and GTF2IRD2) are all highly expressed in the brain, and GTF2I and GTF2IRD1 are involved in the pathogenesis of the cognitive and behavioural phenotypes associated with WBS. A multi-level analysis of cognitive, behavioural and psychological functioning in WBS patients showed that those with slightly larger deletions encompassing GTF2IRD2 were significantly more cognitively impaired in the areas of spatial functioning, social reasoning, and cognitive flexibility (a form of executive functioning). They also displayed significantly more obsessions and externalizing behaviours, a likely manifestation of poor cognitive flexibility and executive dysfunction. We provide the first evidence for a role for GTF2IRD2 in higher-level (executive functioning) abilities and highlight the importance of integrating detailed molecular characterisation of patients with comprehensive neuropsychological profiling to uncover additional genotype-phenotype correlations. The identification of specific genes which contribute to executive function has important neuropsychological implications in the treatment of patients with conditions like WBS, and will allow further studies into their mechanism of action.

A meta-analysis of cognitive deficits in first-episode Major Depressive Disorder.

BACKGROUND: Recurrent-episode Major Depressive Disorder (MDD) is associated with a number of neuropsychological deficits. To date, less is known about whether these are present in the first-episode. The current aim was to systematically evaluate the literature on first-episode MDD to determine whether cognition may be a feasible target for early identification and intervention. METHODS: Electronic database searches were conducted to examine neuropsychological studies in adults (mean age greater than 18 years old) with a first-episode of MDD. Effect sizes were pooled by cognitive domain. Using meta-regression techniques, demographic and clinical factors potentially influencing heterogeneity of neuropsychological outcome were also investigated. RESULTS: The 15 independent samples reviewed yielded data for 644 patients with a mean age of 39.36 years (SD=10.21). Significant cognitive deficits were identified (small to medium effect sizes) for psychomotor speed, attention, visual learning and memory, and all aspects of executive functioning. Symptom remission, inpatient status, antidepressant use, age and educational attainment, each significantly contributed to heterogeneity in effect sizes in at least one cognitive domain. LIMITATIONS: Reviewed studies were limited by small sample sizes and often did not report important demographic and clinical characteristics of patients. CONCLUSIONS: The current meta-analysis was the first to systematically demonstrate reduced neuropsychological functioning in first-episode MDD. Psychomotor speed and memory functioning were associated with clinical state, whereas attention and executive functioning were more likely trait-markers. Demographic factors were also associated with heterogeneity across studies. Overall, cognitive deficits appear to be feasible early markers and targets for early intervention in MDD.

Interpretation of ambiguous situations: evidence for a dissociation between social and physical threat in williams syndrome.

Williams syndrome (WS) is associated with an unusual profile of anxiety, characterised by increased rates of non-social anxiety but not social anxiety (Dodd and Porter, J Ment Health Res Intellect Disabil 2(2):89-109, 2009). The present research examines whether this profile of anxiety is associated with an interpretation bias for ambiguous physical, but not social, situations. Sixteen participants with WS, aged 13-34 years, and two groups of typically developing controls matched to the WS group on chronological age (CA) and mental age (MA), participated. Consistent with the profile of anxiety reported in WS, the WS group were significantly more likely to interpret an ambiguous physical situation as threatening than both control groups. However, no between-group differences were found on the ambiguous social situations.