Age at initial diagnosis of autism spectrum disorders: a retrospective comparison of screening techniques between the southern and northwestern regions of Switzerland.

AIMS: Early diagnosis of autism spectrum disorders (ASD) offers the possibility of early intervention and, in turn, gains in adaptive behaviour, language and cognition. The aim of the present study was to analyse whether age at diagnosis of autism spectrum disorders decreased in two regions of Switzerland from 2006 to 2016 following the implementation of different screening and referral techniques. In southern Switzerland, systematic paediatric screening using the Modified Checklist for Autism (M-CHAT) in toddlers was implemented in 2013, whereas in northwestern Switzerland, periodic trainings were used to increase paediatrician awareness of ASD. We investigated which method was associated with a younger average age at diagnosis. METHODS: We conducted a retrospective, two-centre study searching clinical records of children and adolescents (aged 0-16 years) diagnosed with ASD in two neuropaediatric departments at Swiss hospitals between January 2006 and December 2016. All patients were diagnosed via a standardised evaluation based on two approved diagnostic tests: the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). RESULTS: In southern Switzerland, training and subsequent widespread use of the M-CHAT among paediatricians appeared to contribute to a significantly younger age at diagnosis. Age at diagnosis did not significantly decrease during the same period in northwestern Switzerland. CONCLUSION: Our results point to the possibility of successfully reducing age at diagnosis in specific geographic areas through the implementation of screening questionnaires, such as the M-CHAT, at year 2 well-baby visits.

Emotional vs. Neutral Face Exploration and Habituation: An Eye-Tracking Study of Preschoolers With Autism Spectrum Disorders.

Diminished orienting to social stimuli, and particularly to faces, is a core feature of autism spectrum disorders (ASDs). Impaired face processing has been linked to atypical attention processes that trigger a cascade of pathological development contributing to impaired social communication. The aim of the present study is to explore the processing of emotional and neutral faces using an eye-tracking paradigm (the emotional faces task) with a group of 24 children with ASD aged 6 and under and a group of 22 age-matched typically developing (TD) children. We also measure habituation to faces in both groups based on the presentation of repeated facial expressions. Specifically, the task consists of 32 pairs of faces, a neutral face and an emotional face from the same identity, shown side by side on the screen. We observe differential exploration of emotional faces in preschoolers with ASD compared with TD. Participants with ASD make fewer fixations to emotional faces than their TD peers, and the duration of their first fixation on emotional faces is equivalent to their first fixation on neutral faces. These results suggest that emotional faces may be less interesting for children with ASD. We also observe a habituation process to neutral faces in both children with ASD and TD, who looked less at neutral faces during the last quarter of the task compared with the first quarter. By contrast, TD children show increased interest in emotional faces throughout the task, looking slightly more at emotional faces during the last quarter of the task than during the first quarter. Children with ASD demonstrate neither habituation nor increased interest in the changing emotional expressions over the course of the task, looking at the stimuli for equivalent time throughout the task. A lack of increased interest in emotional faces may suggest a lack of sensitivity to changes in expression in young children with ASD.

Face processing in 22q11.2 deletion syndrome: atypical development and visual scanning alterations.

BACKGROUND: Previous research links social difficulties to atypical face exploration in 22q11.2 deletion syndrome (22q11.2DS). Two types of face processing are distinguished: configural (CFP) and featural (FFP). CFP develops later in life and plays an important role in face and emotion recognition abilities. Recent studies reported atypical development of CFP in several neurodevelopmental disorders. Taking previous reports of atypical face exploration one step further, our study aims at characterizing face processing in children and adolescents with 22q11.2DS. First, we sought to identify biases in the first two fixation positions on faces and to detect differences between CFP and FFP in 22q11.2DS using eye-tracking technology. Second, we investigated the developmental trajectories of CFP and FFP using accuracy data from follow-up evaluation. METHODS: Seventy-five individuals with 22q11.2DS and 84 typically developed (TD) individuals (aged 6-21 years) completed a discrimination task ("Jane task") inducing CFP and FFP in an eye-tracking setting. Thirty-six individuals with 22q11DS and 30 TD from our sample completed a longitudinal follow-up evaluation. RESULTS: Findings revealed that individuals with 22q11.2DS demonstrate an early bias toward the mouth region during the initial fixations on the faces and reduced flexibility exploration of the faces, with a reduced number of transitions between faces and longer fixations compared to the TD group. Further, scanpaths did not differ between CFP and FFP in the 22q11.2DS group. Longitudinal analysis of accuracy data provided evidence for atypical development of CFP in 22q11.2DS. CONCLUSIONS: The current study brings new evidence of altered face exploration in 22q11.2DS and identifies developmental mechanisms that may contribute to difficulties impacting social interactions in the syndrome.

Early Adaptive Functioning Trajectories in Preschoolers With Autism Spectrum Disorders.

Background: In preschoolers with autism spectrum disorder (ASD) symptom, severity has a negative impact on the development of adaptive functioning, with critical consequences on the quality of life of those children. Developmental features such as reduced social interest or the presence of behavioral problems can further impede daily life learning experiences. Objectives: The first aim of this study is to confirm the negative impact of high symptom severity on adaptive functioning trajectories in preschoolers with ASD. The second objective intends to explore whether reduced social interest and severe behavioral problems negatively affect developmental trajectories of adaptive functioning in young children with ASD. Methods: In total, 68 children with ASD and 48 age and gender-matched children with typical development (TD) between 1.6 and 6 years were included in our study, and longitudinal data on adaptive functioning were collected (mean length of the longitudinal data collection was 1.4 years ± 0.6). Baseline measures of symptom severity, social interest, and behavioral problems were also obtained. Results: We confirmed that children with ASD show parallel developmental trajectories but a significantly lower performance of adaptive functioning compared with children with TD. Furthermore, analyses within ASD children demonstrated that those with higher symptom severity, reduced social interest, and higher scores of behavioral problems exhibited especially lower or faster declining trajectories of adaptive functioning. Conclusions: These findings bolster the idea that social interest and behavioral problems are crucial for the early adaptive functioning development of children with autism. The current study has clinical implications in pointing out early intervention targets in children with ASD.

Social orienting and joint attention in preschoolers with autism spectrum disorders.

Children with Autism Spectrum Disorders (ASD) orient less to socially salient stimuli, such as dynamic social images, than typically developing children. In turn, this lack of social orienting is thought to impair affected individuals' socio communicative development. Here, we aim to explore the relationship between time spent on dynamic social images and ASD behaviors, such as joint attention and communication, in preschoolers on the autism spectrum. In this study, social orienting is measured using eye-tracking during a task consisting of side-by-side presentations of dynamic social images and dynamic geometric images. The side of the screen where each type of video was presented alternated between items to avoid visual perseveration from influencing the location of participants' first fixations. Visual exploration patterns recorded during the task from 33 preschoolers with ASD were compared with those of 27 typical developing (TD) children. Additionally, we quantified joint attention behaviors and used standardized parent reports to measure communication. We observed reduced orienting to dynamic social images in preschoolers with ASD compared to TD children. Also, ASD participants went to the dynamic social images less frequently for their first fixations. However, we observed great heterogeneity within the ASD group. ASD preschoolers who spent more time on the dynamic social images also presented more pronounced visual engagement with the dynamic social images (longer mean fixation duration and fewer saccades per second). Moreover, in the ASD group, more time spent on dynamic social images correlated with increased frequency of joint attention behaviors, which in turn correlated with improved communication skills. Our results support reduced social orienting in children with ASD, which correlated with their visual exploration patterns. Further, reduced orienting to the social world in young children with ASD is related to socio communicative deficits and should, therefore, be a focus of intervention programs as early as possible.

Corrigendum: Brief Report: A Preference for Biological Motion Predicts a Reduction in Symptom Severity 1 Year Later in Preschoolers with Autism Spectrum Disorders.

[This corrects the article on p. 143 in vol. 7, PMID: 27605914.].

Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study.

BACKGROUND: Children affected by the 22q11.2 deletion syndrome (22q11.2DS) have a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown that patients with 22q11.2DS have more difficulties memorizing faces and visual-object characteristics of stimuli. In contrast, they have better performance in visuo-spatial memory tasks. The first focus of this study was to replicate these results in a larger sample of patients affected with 22q11.2DS and using a range of memory tasks. Moreover, we analyzed if the deficits were related to brain morphology in the structures typically underlying these abilities (ventral and dorsal visual streams). Finally, since the longitudinal development of visual memory is not clearly characterized in 22q11.2DS, we investigated its evolution from childhood to adolescence. METHODS: Seventy-one patients with 22q11.2DS and 49 control individuals aged between 9 and 16 years completed the Benton Visual Retention Test (BVRT) and specific subtests assessing visual memory from the Children's Memory Scale (CMS). The BVRT was used to compute spatial and object memory errors. For the CMS, specific subtests were classified into ventral, dorsal, and mixed subtests. Longitudinal data were obtained from a subset of 26 patients and 22 control individuals. RESULTS: Cross-sectional results showed that patients with 22q11.2DS were impaired in all visual memory measures, with stronger deficits in visual-object memory and memory of faces, compared to visuo-spatial memory. No correlations between morphological brain impairments and visual memory were found in patients with 22q11.2DS. Longitudinal findings revealed that participants with 22q11.2DS made more object memory errors than spatial memory errors at baseline. This difference was no longer significant at follow-up. CONCLUSIONS: Individuals with 22q11.2DS have impairments in visual memory abilities, with more pronounced difficulties in memorizing faces and visual-object characteristics. From childhood to adolescence, the visual cognitive profile of patients with 22q11.2DS seems globally stable even though some processes show an evolution with time. We hope that our results will help clinicians and caregivers to better understand the memory difficulties of young individuals with 22q11.2DS. This has a particular importance at school to facilitate recommendations concerning intervention strategies for these young patients.

Brief Report: A Preference for Biological Motion Predicts a Reduction in Symptom Severity 1 Year Later in Preschoolers with Autism Spectrum Disorders.

Recent research has consistently demonstrated reduced orienting to social stimuli in samples of young children with autism spectrum disorders (ASD). However, social orienting greatly varies between individual children on the spectrum. Better understanding this heterogeneity in social orienting may contribute to our comprehension of the mechanisms underlying autistic symptoms thereby improving our ability to intervene. Indeed, children on the autism spectrum who show higher levels of interest in social stimuli demonstrate reduced clinical symptoms and increased adaptive functioning. However, longitudinal studies examining the influence of social orienting on subsequent outcome are critically lacking. Here, we aim to explore the relationship between social interest at the age of 3 and changes in severity of autistic symptoms over the subsequent year, in 20 children with ASD and 20 age-matched typically developing (TD) children. A visual preference for social stimuli was measured using an eye-tracking task at baseline, consisting of a previously studied visual preference paradigm presenting biological and geometric motion side-by-side. The task was altered for the current study by alternating presentation side for each type of stimuli to keep visual perseveration from influencing participants' first fixation location. Clinical data were collected both at baseline and 1 year later at follow-up. As a group, we observed reduced interest for biological motion (BIO-M) in children with ASD compared to TD children, corroborating previous findings. We also confirmed that a preference for BIO-M is associated with better adaptive functioning in preschoolers with ASD. Most importantly, our longitudinal results showed that a preference for BIO-M strongly predicted decreased severity of diagnostic symptoms. Participants who preferred social stimuli at the age of 3 showed drastic reductions in their severity level of autistic symptoms 1 year later, whereas participants who preferred geometric stimuli showed autistic symptoms that were unchanged or more severe after 1 year. As a whole, our results suggest that a preference for BIO-M may be key to understanding the behavioral phenotype of young children with ASD, and may represent a promising candidate behavior for predicting early developmental trajectories and outcome.

Developmental trajectories of executive functions in 22q11.2 deletion syndrome.

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder associated with a specific cognitive profile. Higher-order cognitive skills like executive functions (EF) are reported as a relative weakness in this population. The present study aimed to delineate the developmental trajectories of multiple EF domains in a longitudinal sample using a broader age range than previous studies. Given the high incidence of psychotic symptoms in 22q11.2DS, we also compared the development of EF in participants with/without comorbid psychotic symptoms. Given the importance of EF in daily life, the third aim of the study was to characterize the link between EF and adaptive functioning. METHODS: The sample consisted of 95 individuals with 22q11.2DS and 100 typically developing controls aged 6-26 years. A large proportion of the sample (55.38 %) had multiple time points available. Between-group differences in the developmental trajectories of three subdomains of EF (verbal fluency, working memory, and inhibition) were examined using mixed models regression analyses. Analyses were repeated comparing only the 22q11.2DS group based on the presence/absence of psychotic symptoms to investigate the influence of executive dysfunction on the emergence of psychotic symptoms. Hierarchical stepwise regression analyses were also conducted to investigate the predictive value of EF on adaptive functioning. RESULTS: We observed lower performance on EF domains, as well as atypical development of working memory and verbal fluency. Participants who presented with negative symptoms exhibited different developmental trajectories of inhibition and working memory. Adaptive functioning level was not significantly predicted by EF scores. CONCLUSIONS: The present study highlighted domain-specific atypical trajectories of EF in individuals with 22q11.DS and explored the link with psychotic symptoms. However, no relation between EF and adaptive functioning was observed.

Individuals with 22q11.2 deletion syndrome are impaired at explicit, but not implicit, discrimination of local forms embedded in global structures.

Individuals with 22q11.2 deletion syndrome (22q11.2DS) are impaired at exploring visual information in space; however, not much is known about visual form discrimination in the syndrome. Thirty-five individuals with 22q11.2DS and 41 controls completed a form discrimination task with global forms made up of local elements. Affected individuals demonstrated clear impairment in detecting local, but not global, differences. Nevertheless, 22q11.2DS participants easily discriminated the same local elements when they were displayed in isolation, and further use of a prime demonstrated preserved facilitation of local processing in 22q11.2DS. These results did not differ by age or IQ. This study illustrates the impact of visuospatial impairments on form discrimination, and suggests how these difficulties may affect visual scanning in 22q11.2DS.

Predominant negative symptoms in 22q11.2 deletion syndrome and their associations with cognitive functioning and functional outcome.

22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic condition associated with increased risk for schizophrenia. No study do date has explored how positive and negative symptoms of psychosis are distributed among individual patients with 22q11.2DS and if distinct patterns of symptoms can be identified. Negative symptoms being more frequent than positive symptoms in 22q11.2DS, we expected that a high number of patients would display predominant negative symptoms (PNS), whereas predominant positive symptoms would be less frequently reported. The present study aims at investigating the cognitive deficits and functional outcome associated with distinct patterns of psychotic symptoms in 22q11.2DS. 63 adolescents and young adults with 22q11.2DS participated in this study. Each participant underwent a clinical and a cognitive evaluation. A cluster analysis was used to identify groups of individuals with distinct patterns of symptoms. Individuals from the different clusters were then compared on a series of cognitive measures and on functional outcome. Three clusters of individuals were identified: low levels of symptoms, PNS, and high levels of symptoms. Individuals with PNS had significantly lower visual memory scores and decreased processing speed compared to participants with low levels of symptoms. They were also rated as having lower functional and occupational outcome. The present results indicate that one third of adolescents and young adults with 22q11.2DS display PNS. This pattern of symptoms was associated with specific cognitive deficits and decreased functional outcome. Future studies are needed to examine the developmental trajectories of these individuals and assess their risk of conversion to full-blown psychosis.

Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach.

22q11.2 deletion syndrome (22q11DS) is associated with increased risk for schizophrenia. Better identifying risk factors for the emergence of psychotic symptoms in this population is needed to improve clinical assessment and early interventions. Schizophrenia spectrum disorders, hallucinations and delusions were characterized in an original sample of 104 individuals with 22q11DS. Further analysis of positive and negative symptoms was performed in a subsample of 59 individuals. Finally, longitudinal data available in 56 patients were used to explore the developmental trajectories of psychotic symptoms as well as the associations between psychotic symptoms and cognitive functioning. Schizophrenia spectrum disorders and psychotic symptoms were frequent in adolescent and adults with 22q11DS. The severity of hallucinations and non-persecutory delusional ideas discriminated patients at ultra-high risk for conversion to psychosis. Whereas approximately one-third of patients experienced an emergence of psychotic symptoms during a 4-year interval, 20 % displayed transient symptoms. Individuals with psychotic symptoms were characterized by a lower cognitive functioning in the context of the 22q11DS. The present study adds important data on the characteristics and developmental trajectory of psychotic symptoms in this population. This information may ultimately help clinicians dealing with these patients to reduce the duration of untreated psychosis and improve outcome.

Decreased frontal gyrification correlates with altered connectivity in children with autism.

The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anisotropy (FA) and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism.

Risk factors and the evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal 2-site study.

OBJECTIVE: 22q11.2 Deletion syndrome (22q11.2DS) is associated with high rates of schizophrenia, other neuropsychiatric disorders, and cognitive deficits. The objectives of this 2-center study were to longitudinally assess the trajectories of psychiatric disorders in 22q11.2DS from childhood to adulthood, and to identify risk factors for their emergence. METHOD: A total of 125 children and adults with 22q11.2DS were evaluated at 2 time points, baseline and follow-up (4 years apart), using standardized psychiatric and cognitive measures. RESULTS: The rate of mood disorders tended to decrease during childhood and increase during late adolescence. Statistically significant predictors for the presence of a psychotic disorder as well as the severity of positive symptoms at follow-up were identical, and consisted of an anxiety disorder at baseline, lower baseline Full Scale IQ, and a greater decrease in verbal IQ scores between time points. Nine of 10 individuals with an emerging psychotic disorder had an anxiety disorder at baseline. The age of onset for a psychotic disorder was between 14 and 22 years in 82.6% of cases. CONCLUSIONS: It is important to evaluate the presence of anxiety disorders in children and adolescents with 22q11.2DS, as they are major risk factors for the emergence of psychotic disorders, which usually occur during late adolescence in this at-risk population.

Candidate socioemotional remediation program for individuals with intellectual disability.

The authors developed a computerized program, Vis-à-Vis (VAV), to improve socioemotional functioning and working memory in children with developmental disabilities. The authors subsequently tested whether participants showed signs of improving the targeted skills. VAV is composed of three modules: Focus on the Eyes, Emotion Recognition and Understanding, and Working Memory. Ten children with idiopathic developmental delay completed four 20-min weekly sessions of VAV for 12 weeks with an adult. Participants were evaluated before (Time 0) and after (Time 1) training and 6 months after remediation (Time 2). Subjects improved on all three modules during training and on emotion recognition and nonverbal reasoning post-VAV. These gains were still present at Time 2. VAV is a promising new tool for working on socioemotional impairments in hard-to-treat pediatric populations.

Preliminary structure and predictive value of attenuated negative symptoms in 22q11.2 deletion syndrome.

Current research in schizophrenia suggests that negative symptoms cannot be considered a unitary construct and should be divided in two dimensions: lack of motivation and impoverishment of expression. In addition, negative symptoms are particularly related to decreased daily-life functioning. In the present study, we aimed to replicate these results in a sample of participants with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition associated with high risk of developing schizophrenia. We also expected to observe an association between the COMT Val/Met polymorphism and negative symptoms. We examined the factorial structure of negative symptoms in a sample of 47 individuals with 22q11DS using the Structured Interview for Prodromal Symptoms (SIPS) and the Positive and Negative Syndrome Scale (PANSS). We also performed stepwise regression analyses to investigate the associations between negative symptoms, adaptive skills and the COMT Val/Met polymorphism. Negative symptoms were explained by a two-factor solution, namely the "amotivation and social withdrawal" and the "emotional withdrawal and expression" dimensions. The motivational dimension was significantly associated with daily-life functioning. Met carriers were rated as experiencing significantly more symptoms of amotivation. The results are interpreted in the light of existing cognitive models in the field of motivation and schizophrenia.

Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome.

Children with congenital heart disease (CHD) who survive surgery often present impaired neurodevelopment and qualitative brain anomalies. However, the impact of CHD on total or regional brain volumes only received little attention. We address this question in a sample of patients with 22q11.2 deletion syndrome (22q11DS), a neurogenetic condition frequently associated with CHD. Sixty-one children, adolescents, and young adults with confirmed 22q11.2 deletion were included, as well as 80 healthy participants matched for age and gender. Subsequent subdivision of the patients group according to CHD yielded a subgroup of 27 patients with normal cardiac status and a subgroup of 26 patients who underwent cardiac surgery during their first years of life (eight patients with unclear status were excluded). Regional cortical volumes were extracted using an automated method and the association between regional cortical volumes, and CHD was examined within a three-condition fixed factor. Robust protection against type I error used Bonferroni correction. Smaller total cerebral volumes were observed in patients with CHD compared to both patients without CHD and controls. The pattern of bilateral regional reductions associated with CHD encompassed the superior parietal region, the precuneus, the fusiform gyrus, and the anterior cingulate cortex. Within patients, a significant reduction in the left parahippocampal, the right middle temporal, and the left superior frontal gyri was associated with CHD. The present results of global and regional volumetric reductions suggest a role for disturbed hemodynamic in the pathophysiology of brain alterations in patients with neurodevelopmental disease and cardiac malformations.

Eye gaze during face processing in children and adolescents with 22q11.2 deletion syndrome.

OBJECTIVE: The 22q11.2 deletion syndrome (22q11DS) is a neurogenetic syndrome with high risk for the development of psychiatric disorder. There is interest in identifying reliable markers for measuring and monitoring socio-emotional impairments in 22q11DS during development. The current study investigated eye gaze as a potential marker during a face-processing task in children and young adolescents with 22q11DS. METHOD: Eye gaze and behavioral correlates were investigated in 26 subjects (aged 8 to 15 years) with 22q11DS during the Jane Task, which targets featural and configural face processing. Individuals with 22q11DS were compared with chronologically age-matched healthy controls and individuals with idiopathic developmental delay (DD). RESULTS: Few differences in accuracy were observed between patients with 22q11DS and DD controls; however individuals with 22q11DS spent less time on the eyes and more time on the mouths than both comparison groups. IQ predicted time on the eyes in subjects with 22q11DS, and anxiety predicted time on the eyes in DD and 22q11DS subjects. CONCLUSIONS: These results provide evidence for abnormal exploration of faces in the syndrome and suggest that time spent on the eyes may contribute to face processing difficulties and interact with anxiety levels to exacerbate socio-emotional dysfunction in affected individuals.

Monitoring of self-generated speech in adolescents with 22q11.2 deletion syndrome.

OBJECTIVES: The present report examines the monitoring of self-generated speech in adolescents with 22q11.2 deletion syndrome (22q11DS), a neurogenetic disorder associated with very high risk for psychosis. DESIGN: Between-participant group design. METHODS: In this study, 20 adolescents with 22q11DS, 19 age- and IQ-matched controls, and 19 typically developing adolescents were enrolled. Participants completed a speech-monitoring task, in which they were asked to silently or overtly read a series of word and non-word items. Subjects then filled out a recognition sheet containing studied and novel items. They were asked to identify the previously studied item, and to attribute the reading condition (silent vs. overt) under which each recognized item was encoded. RESULTS: Adolescents with 22q11DS commit more external attribution errors compared to both control groups, by exhibiting an increased tendency to report silently read items as though they had been read overtly. Further, results suggest that increased cognitive effort exacerbates the external attribution tendency in adolescents with 22q11DS. Increased internal attributions were also observed in the IQcontrol and 22q11DS groups in comparison to typically developing adolescents. CONCLUSIONS: Similarly to adult individuals exhibiting positive symptoms of psychosis, adolescents with 22q11DS exhibit an external attribution bias for inner speech. This bias seems to be exacerbated by increased cognitive effort, suggesting a failure to recollect information pertaining to cognitive operations during self-monitoring. Cognitive biases associated to schizophrenia may be detected in adolescents at very high risk for psychosis. These observations provide further evidence for the presence of an external attribution bias along the clinical continuum of psychosis vulnerability.

Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome.

OBJECTIVE: Velocardiofacial syndrome (VCFS) is associated with cognitive deficits and high rates of schizophrenia and other neuropsychiatric disorders. We report the data from two large cohorts of individuals with VCFS from Israel and Western Europe to characterize the neuropsychiatric phenotype from childhood to adulthood in a large sample. METHOD: Individuals with VCFS (n = 172) aged 5 to 54 years were evaluated with structured clinical interviews for psychiatric disorders and age-appropriate versions of the Wechsler intelligence tests. RESULTS: The frequency of psychiatric disorders was high and remarkably similar between samples. Psychotic disorders and depression were uncommon during childhood but increased in rates during adulthood (depressive disorders: 40.7% in young adults [aged 18-24 years]; psychotic disorders: 32.1% in adults [age >24 years]). Cognitive scores were inversely associated with age in subjects with VCFS, including patients without psychosis. Specifically, Verbal IQ (VIQ) scores negatively correlated with age, and the subjects with VCFS and psychotic disorders had significantly lower VIQ scores than nonpsychotic VCFS subjects. CONCLUSIONS: Neuropsychiatric deficits in individuals with VCFS seem to follow a developmental pattern. The VIQ scores are negatively associated with age and rates of mood, and psychotic disorders increase dramatically during young adulthood. The data presented here support careful monitoring of psychiatric symptoms during adolescence and young adulthood in VCFS. Prospective longitudinal studies are needed to examine the nature of age-related cognitive changes and their association with psychiatric morbidity in VCFS.