An fMRI study of facial emotion processing in children and adolescents with 22q11.2 deletion syndrome

Background

22q11.2 deletion syndrome (22q11DS, velo-cardio-facial syndrome [VCFS]) is a genetic disorder associated with interstitial deletions of chromosome 22q11.2. In addition to high rates of neuropsychiatric disorders, children with 22q11DS have impairments of face processing, as well as IQ-independent deficits in visuoperceptual function and social and abstract reasoning. These face-processing deficits may contribute to the social impairments of 22q11DS. However, their neurobiological basis is poorly understood.

Methods

We used event-related functional magnetic resonance imaging (fMRI) to examine neural responses when children with 22q11DS (aged 9–17 years) and healthy controls (aged 8–17 years) incidentally processed neutral expressions and mild (50%) and intense (100%) expressions of fear and disgust. We included 28 right-handed children and adolescents: 14 with 22q11DS and 14 healthy (including nine siblings) controls.

Results

Within groups, contrasts showed that individuals significantly activated ‘face responsive’ areas when viewing neutral faces, including fusiform-extrastriate cortices. Further, within both groups, there was a significant positive linear trend in activation of fusiform-extrastriate cortices and cerebellum to increasing intensities of fear. There were, however, also between-group differences. Children with 22q11DS generally showed reduced activity as compared to controls in brain regions involved in social cognition and emotion processing across emotion types and intensities, including fusiform-extrastriate cortices, anterior cingulate cortex (Brodmann area (BA) 24/32), and superomedial prefrontal cortices (BA 6). Also, an exploratory correlation analysis showed that within 22q11DS children reduced activation was associated with behavioural impairment—social difficulties (measured using the Total Difficulties Score from the Strengths and Difficulties Questionnaire [SDQ]) were significantly negatively correlated with brain activity during fear and disgust processing (respectively) in the left precentral gyrus (BA 4) and in the left fusiform gyrus (FG, BA 19), right lingual gyrus (BA 18), and bilateral cerebellum.

Conclusions

Regions involved in face processing, including fusiform-extrastriate cortices, anterior cingulate gyri, and superomedial prefrontal cortices (BA 6), are activated by facial expressions of fearful, disgusted, and neutral expressions in children with 22q11DS but generally to a lesser degree than in controls. Hypoactivation in these regions may partly explain the social impairments of children with 22q11DS.

Electronic supplementary material

The online version of this article (doi:10.1186/1866-1955-7-1) contains supplementary material, which is available to authorized users.     

Pre-pulse inhibition and antisaccade performance indicate impaired attention modulation of cognitive inhibition in 22q11.2 deletion syndrome (22q11DS)

Background

22q11.2 deletion syndrome (22q11DS) is associated with a number of physical anomalies and neuropsychological deficits including impairments in executive and sensorimotor function. It is estimated that 25% of children with 22q11DS will develop schizophrenia and other psychotic disorders later in life. Evidence of genetic transmission of information processing deficits in schizophrenia suggests performance in 22q11DS individuals will enhance understanding of the neurobiological and genetic substrates associated with information processing. In this report, we examine information processing in 22q11DS using measures of startle eyeblink modification and antisaccade inhibition to explore similarities with schizophrenia and associations with neurocognitive performance.

Methods

Startle modification (passive and active tasks; 120- and 480-ms pre-pulse intervals) and antisaccade inhibition were measured in 25 individuals with genetically confirmed 22q11DS and 30 healthy control subjects.

Results

Individuals with 22q11DS exhibited increased antisaccade error as well as some evidence (trend-level effect) of impaired sensorimotor gating during the active condition, suggesting a dysfunction in controlled attentional processing, rather than a pre-attentive dysfunction using this paradigm.

Conclusions

The findings from the present study show similarities with previous studies in clinical populations associated with 22q11DS such as schizophrenia that may indicate shared dysfunction of inhibition pathways in these groups.     

Common and specific impairments in attention functioning in girls with chromosome 22q11.2 deletion,fragile X or Turner syndromes

Background

Chromosome 22q11.2 deletion syndrome (22q11.2DS), fragile X syndrome (FXS), and Turner syndrome (TS) are complex and variable developmental syndromes caused by different genetic abnormalities; yet, they share similar cognitive impairments in the domains of numbers, space, and time. The atypical development of foundational neural networks that underpin the attentional system is thought to result in further impairments in higher-order cognitive functions. The current study investigates whether children with similar higher-order cognitive impairments but different genetic disorders also show similar impairments in alerting, orienting, and executive control of attention.

Methods

Girls with 22q11.2DS, FXS, or TS and typically developing (TD) girls, aged 7 to 15 years, completed an attention network test, a flanker task with alerting and orienting cues. Exploration of reaction times and accuracy allowed us to test for potential commonalities in attentional functioning in alerting, orienting, and executive control. Linear regression models were used to test whether the predictors of group and chronological age were able to predict differences in attention indices.

Results

Girls with 22q11.2DS, FXS, or TS demonstrated unimpaired function of the alerting system and impaired function of the executive control system. Diagnosis-specific impairments were found such that girls with FXS made more errors and had a reduced orienting index, while girls with 22q11.2DS showed specific age-related deficits in the executive control system.

Conclusions

These results suggest that the control but not the implementation of attention is selectively impaired in girls with 22q11.2DS, TS or FXS. Additionally, the age effect on executive control in girls with 22q11.2DS implies a possible altered developmental trajectory.     

A comparative study of cognition and brain anatomy between two neurodevelopmental disorders: 22q11.2 deletion syndrome and Williams syndrome

Background

22q11.2 deletion syndrome (22q11DS) is associated with intellectual disability, poor social interaction and a high prevalence of psychosis. However, to date there have been no studies comparing cognition and neuroanatomical characteristics of 22q11DS with other syndromes to investigate if the cognitive strengths and difficulties and neuroanatomical differences associated with 22q11DS are specific to the syndrome. Hence, it is difficult to know if the observed features of 22q11DS are simply due to a non-specific effect of having a genetic disorder or are specific to 22q11DS.

Methods

In this study, cognition and brain anatomy of 12 children with 22q11DS were compared to 12 age, gender and full scale IQ (FSIQ) matched children with William syndrome (WS) in order to investigate which cognitive and neuroanatomical features are specific to 22q11DS. We chose WS since the literature suggests that both groups have areas of physical/cognitive/behavioural overlap but as yet there has been no direct comparison of the two groups.

Results

Despite being matched on FSIQ the WS group had significantly greater impairment than those with 22q11DS on tests of Performance IQ, while performing significantly better on tasks measuring verbal, social and facial processing skills. Moreover there were significant differences in brain anatomy. Despite similar overall brain volumes, midline anomalies were more common among the 22q11DS group, and regional differences such as increased striatal volumes and reduced cerebellar volumes in the 22q11DS group were detected.

Conclusions

These findings suggest that although the behavioural phenotype is similar in some aspects there are key differences in cognition and neuroanatomy between the two groups. Different neuropsychological profiles need to be considered when designing educational frameworks for working with these children.     

Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome

Background

The neural endophenotype associated with 22q11.2 deletion syndrome (22q11DS) includes deviant cortical development and alterations in brain connectivity. Resting-state functional magnetic resonance imaging (fMRI) findings also reported disconnectivity within the default mode network (DMN). In this study, we explored the relationship between functional and structural DMN connectivity and their changes with age in patients with 22q11DS in comparison to control participants. Given previous evidence of an association between DMN disconnectivity and the manifestation of psychotic symptoms, we further investigated this relationship in our group of patients with 22q11DS.

Methods

T1-weighted, diffusion, and resting-state fMRI scans were acquired from 41 patients with 22q11DS and 43 control participants aged 6 to 28 years. A data-driven approach based on independent component analysis (ICA) was used to identify the DMN and to define regions of interest for the structural and functional connectivity analysis. Prodromal psychotic symptoms were assessed in adolescents and adults using the positive symptom scores of the Structured Interview of Prodromal Syndromes (SIPS). Connectivity measures were compared between groups and correlated with age. Repeating the between-group analysis in three different age bins further assessed the presence of age-related alterations in DMN connectivity. Structural and functional connectivity measures were then correlated with the SIPS scores.

Results

A simultaneous reduction of functional and structural connectivity between core medial nodes of the DMN was observed. Furthermore, structural connectivity measures significantly increased with age in the control group but not in patients with 22q11DS, suggesting the presence of an age-related alteration of the DMN structural connections. No correlations were found between the DMN disconnectivity and expression of prodromal symptoms in 22q11DS.

Conclusions

These findings indicate the presence of functional and structural DMN disconnectivity in 22q11DS and that patients with 22q11DS fail to develop normal structural connections between medial DMN nodes. This suggests the presence of altered neurodevelopmental trajectories in 22q11DS.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9120-y) contains supplementary material, which is available to authorized users.     

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.

     

Frontal dysconnectivity in 22q11.2 deletion syndrome: an atlas-based functional connectivity analysis

Background

22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental syndrome associated with deficits in cognitive and emotional processing. This syndrome represents one of the highest risk factors for the development of schizophrenia. Previous studies of functional connectivity (FC) in 22q11DS report aberrant connectivity patterns in large-scale networks that are associated with the development of psychotic symptoms.

Methods

In this study, we performed a functional connectivity analysis using the CONN toolbox to test for differential connectivity patterns between 54 individuals with 22q11DS and 30 healthy controls, between the ages of 17–25 years old. We mapped resting-state fMRI data onto 68 atlas-based regions of interest (ROIs) generated by the Desikan-Killany atlas in FreeSurfer, resulting in 2278 ROI-to-ROI connections for which we determined total linear temporal associations between each. Within the group with 22q11DS only, we further tested the association between prodromal symptoms of psychosis and FC.

Results

We observed that relative to controls, individuals with 22q11DS displayed increased FC in lobar networks involving the frontal–frontal, frontal–parietal, and frontal–occipital ROIs. In contrast, FC between ROIs in the parietal–temporal and occipital lobes was reduced in the 22q11DS group relative to healthy controls. Moreover, positive psychotic symptoms were positively associated with increased functional connections between the left precuneus and right superior frontal gyrus, as well as reduced functional connectivity between the bilateral pericalcarine. Positive symptoms were negatively associated with increased functional connectivity between the right pericalcarine and right postcentral gyrus.

Conclusions

Our results suggest that functional organization may be altered in 22q11DS, leading to disruption in connectivity between frontal and other lobar substructures, and potentially increasing risk for prodromal psychosis.

     

The social brain network in 22q11.2 deletion syndrome: a diffusion tensor imaging study

Background

Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic disorder that is associated with a 25-fold increase in schizophrenia. Both individuals with 22q11.2DS and those with schizophrenia present with social cognitive deficits, which are putatively subserved by a network of brain regions that are involved in the processing of social cognitive information. This study used two-tensor tractography to examine the white matter tracts believed to underlie the social brain network in a group of 57 young adults with 22q11.2DS compared to 30 unaffected controls.

Results

Results indicated that relative to controls, participants with 22q11.2DS showed significant differences in several DTI metrics within the inferior fronto-occipital fasciculus, cingulum bundle, thalamo-frontal tract, and inferior longitudinal fasciculus. In addition, participants with 22q11.2DS showed significant differences in scores on measures of social cognition, including the Social Responsiveness Scale and Trait Emotional Intelligence Questionnaire. Further analyses among individuals with 22q11.2DS demonstrated an association between DTI metrics and positive and negative symptoms of psychosis, as well as differentiation between individuals with 22q11.2DS and overt psychosis, relative to those with positive prodromal symptoms or no psychosis.

Conclusions

Findings suggest that white matter disruption, specifically disrupted axonal coherence in the right inferior fronto-occipital fasciculus, may be a biomarker for social cognitive difficulties and psychosis in individuals with 22q11.2DS.

     

A comparative study of the neuropsychiatric and neurocognitive phenotype in two microdeletion syndromes: Velocardiofacial (22q11.2 deletion) and Williams (7q11.23 deletion) syndromes

Purpose22q11.2 deletion syndrome (22q11.2DS) and Williams syndrome (WS) are common neurogenetic microdeletion syndromes. The aim of the present study was to compare the neuropsychiatric and neurocognitive phenotypes of 22q11.2DS and WS.MethodsForty-five individuals with 22q11.2DS, 24 with WS, 22 with idiopathic developmental disability (DD) and 22 typically developing (TD) controls were compared for the rates of psychiatric disorders as well as cognitive executive and visuospatial functions.ResultsWe found that while anxiety, mood and disruptive disorders had an equally high prevalence among individuals with 22q11.2DS, WS and DDs, the 22q11.2DS group had the highest rates of psychotic disorders and the WS group had the highest rates of specific phobia. We also found that the WS group demonstrated more severe impairments in both executive and visuospatial functions than the other groups. WS and 22q11.2DS subjects had worse Performance-IQ than Verbal-IQ, a feature typical of non-verbal learning disorders.ConclusionThese findings offer a wide perspective on unique versus common phenotypes in 22q11.2DS and WS.     

Abnormalities in brain white matter in adolescents with 22q11.2 deletion syndrome and psychotic symptoms

Background

22q11.2 Deletion Syndrome (22q11DS) is considered to be a promising cohort to explore biomarkers of schizophrenia risk based on a 30 % probability of developing schizophrenia in adulthood. In this study, we investigated abnormalities in the microstructure of white matter in adolescents with 22q11DS and their specificity to prodromal symptoms of schizophrenia.

Methods

Diffusion Magnetic Resonance Imaging (dMRI) data were acquired from 50 subjects with 22q11DS (9 with and 41 without prodromal psychotic symptoms), and 47 matched healthy controls (mean age 18 +/?2 years). DMRI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated and compared between groups using the Tract Based Spatial Statistics (TBSS) method. Additionally, correlations between dMRI measures and scores on positive symptoms were performed.

Results

Reductions in MD, AD and RD (but not FA) were found in the corpus callosum (CC), left and right superior longitudinal fasciculus (SLF), and left and right corona radiata in the entire 22q11DS group. In addition, the 22q11DS subgroup with prodromal symptoms showed reductions in AD and MD, but no changes in RD when compared to the non-prodromal subgroup, in CC, right SLF, right corona radiata and right internal capsule. Finally, AD values in these tracts correlated with the scores on the psychosis subscale.

Conclusion

Microstructural abnormalities in brain white matter are present in adolescent subjects with prodromal psychotic symptoms.

     

Comparative mapping of the 22q11.2 deletion region and the potential of simple model organisms

Background

22q11.2 deletion syndrome (22q11.2DS) is the most common micro-deletion syndrome. The associated 22q11.2 deletion conveys the strongest known molecular risk for schizophrenia. Neurodevelopmental phenotypes, including intellectual disability, are also prominent though variable in severity. Other developmental features include congenital cardiac and craniofacial anomalies. Whereas existing mouse models have been helpful in determining the role of some genes overlapped by the hemizygous 22q11.2 deletion in phenotypic expression, much remains unknown. Simple model organisms remain largely unexploited in exploring these genotype-phenotype relationships.

Methods

We first developed a comprehensive map of the human 22q11.2 deletion region, delineating gene content, and brain expression. To identify putative orthologs, standard methods were used to interrogate the proteomes of the zebrafish (D. rerio), fruit fly (D. melanogaster), and worm (C. elegans), in addition to the mouse. Spatial locations of conserved homologues were mapped to examine syntenic relationships. We systematically cataloged available knockout and knockdown models of all conserved genes across these organisms, including a comprehensive review of associated phenotypes.

Results

There are 90 genes overlapped by the typical 2.5 Mb deletion 22q11.2 region. Of the 46 protein-coding genes, 41 (89.1 %) have documented expression in the human brain. Identified homologues in the zebrafish (n = 37, 80.4 %) were comparable to those in the mouse (n = 40, 86.9 %) and included some conserved gene cluster structures. There were 22 (47.8 %) putative homologues in the fruit fly and 17 (37.0 %) in the worm involving multiple chromosomes. Individual gene knockdown mutants were available for the simple model organisms, but not for mouse. Although phenotypic data were relatively limited for knockout and knockdown models of the 17 genes conserved across all species, there was some evidence for roles in neurodevelopmental phenotypes, including four of the six mitochondrial genes in the 22q11.2 deletion region.

Conclusions

Simple model organisms represent a powerful but underutilized means of investigating the molecular mechanisms underlying the elevated risk for neurodevelopmental disorders in 22q11.2DS. This comparative multi-species study provides novel resources and support for the potential utility of non-mouse models in expression studies and high-throughput drug screening. The approach has implications for other recurrent copy number variations associated with neurodevelopmental phenotypes.

Electronic supplementary material

The online version of this article (doi:10.1186/s11689-015-9113-x) contains supplementary material, which is available to authorized users.     

Neural correlates of socio-emotional perception in 22q11.2 deletion syndrome

Background

Social impairments are described as a common feature of the 22q11.2 deletion syndrome (22q11DS). However, the neural correlates underlying these impairments are largely unknown in this population. In this study, we investigated neural substrates of socio-emotional perception.

Methods

We used event-related functional magnetic resonance imaging (fMRI) to explore neural activity in individuals with 22q11DS and healthy controls during the visualization of stimuli varying in social (social or non-social) or emotional (positive or negative valence) content.

Results

Neural hyporesponsiveness in regions of the default mode network (inferior parietal lobule, precuneus, posterior and anterior cingulate cortex and frontal regions) in response to social versus non-social images was found in the 22q11DS population compared to controls. A similar pattern of activation for positive and negative emotional processing was observed in the two groups. No correlation between neural activation and social functioning was observed in patients with the 22q11DS. Finally, no social × valence interaction impairment was found in patients.

Conclusions

Our results indicate atypical neural correlates of social perception in 22q11DS that appear to be independent of valence processing. Abnormalities in the social perception network may lead to social impairments observed in 22q11DS individuals.

     

Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: a longitudinal study

The 22q11.2 deletion syndrome (22q11.2DS) is associated with very high rates of schizophrenia-like psychosis and cognitive deficits. Here we report the results of the first longitudinal study assessing brain development in individuals with 22q11.2DS. Twenty-nine children with 22q11.2DS and 29 age and gender matched controls were first assessed during childhood or early adolescence; Nineteen subjects with 22q11.2DS and 18 controls underwent follow-up during late adolescence-early adulthood. The 22q11.2DS subjects showed greater longitudinal increase in cranial and cerebellar white matter, superior temporal gyrus, and caudate nucleus volumes. They also had a more robust decrease in amygdala volume. Verbal IQ (VIQ) scores of the 22q11.2DS group that developed psychotic disorders declined significantly between assessments. Decline in VIQ in 22q11.2DS was associated with more robust reduction of left cortical grey matter volume. No volumetric differences were detected between psychotic and nonpsychotic subjects with 22q11.2DS. Brain maturation associated with verbal cognitive development in 22q11.2DS varies from that observed in healthy controls. Further longitudinal studies are likely to elucidate brain developmental trajectories in 22q11.2DS and their association to psychotic disorders and cognitive deficits in this population.     

Parental report on socio-communicative behaviours in children with 22q11.2 deletion syndrome

Background Children with 22q11.2 deletion syndrome (22q11.2DS) are reported to have socio-communicative impairments. Although many of these children are diagnosed with intellectual disability (ID) and/or autism spectrum disorder (ASD), these populations are seldom used as control groups. Hence, information regarding syndrome-specific socio-communicative challenges is lacking.

Method Parental concerns regarding everyday communication were investigated by means of the Children’s Communication Checklist-2-NL (Geurts, 2007). Twenty children with 22q11.2DS (chronological age: 6 years–13 years 3 months) were compared to 21 children with idiopathic ID and 23 children with idiopathic ID and comorbid ASD. All groups were matched for fluid intelligence (Gf), chronological age, and core language scores.

Results Neglect or inadequate use of context information was more prevalent in children with 22q11.2DS than in children with idiopathic ID. Nonverbal communication seemed less impaired than in children with idiopathic ID + ASD.

Conclusion Pragmatic language skills and developmental trajectories in children with 22q11.2DS merit further investigation.     

Visual perception and processing in children with 22q11.2 deletion syndrome: associations with social cognition measures of face identity and emotion recognition

Background

People with 22q11.2 deletion syndrome (22q11DS) have difficulty processing social information including facial identity and emotion processing. However, difficulties with visual and attentional processes may play a role in difficulties observed with these social cognitive skills.

Methods

A cross-sectional study investigated visual perception and processing as well as facial processing abilities in a group of 49 children and adolescents with 22q11DS and 30 age and socio-economic status-matched healthy sibling controls using the Birmingham Object Recognition Battery and face processing sub-tests from the MRC face processing skills battery.

Results

The 22q11DS group demonstrated poorer performance on all measures of visual perception and processing, with greatest impairment on perceptual processes relating to form perception as well as object recognition and memory. In addition, form perception was found to make a significant and unique contribution to higher order social-perceptual processing (face identity) in the 22q11DS group.

Conclusions

The findings indicate evidence for impaired visual perception and processing capabilities in 22q11DS. In turn, these were found to influence cognitive skills needed for social processes such as facial identity recognition in the children with 22q11DS.

     

Developmental changes in multivariate neuroanatomical patterns that predict risk for psychosis in 22q11.2 deletion syndrome

The primary objective of the current prospective study was to examine developmental patterns of voxel-by-voxel gray and white matter volumes (GMV, WMV, respectively) that would predict psychosis in adolescents with 22q11.2 deletion syndrome (22q11.2DS), the most common known genetic risk factor for schizophrenia. We performed a longitudinal voxel-based morphometry analysis using structural T1 MRI scans from 19 individuals with 22q11.2DS and 18 typically developing individuals. In 22q11.2DS, univariate analysis showed that greater reduction in left dorsal prefrontal cortical (dPFC) GMV over time predicted greater psychotic symptoms at Time2. This dPFC region also showed significantly reduced volumes in 22q11.2DS compared to typically developing individuals at Time1 and 2, greater reduction over time in 22q11.2DS COMT^Met compared to COMT^Val, and greater reduction in those with greater decline in verbal IQ over time. Leave-one-out Multivariate pattern analysis results (MVPA) on the other hand, showed that patterns of GM and WM morphometric changes over time in regions including but not limited to the dPFC predicted risk for psychotic symptoms (94.7-100% accuracy) significantly better than using univariate analysis (63.1%). Additional predictive brain regions included medial PFC and dorsal cingulum. This longitudinal prospective study shows novel evidence of morphometric spatial patterns predicting the development of psychotic symptoms in 22q11.2DS, and further elucidates the abnormal maturational processes in 22q11.2DS. The use of neuroimaging using MVPA may hold promise to predict outcome in a variety of neuropsychiatric disorders.     

Associations between social cognition,skills, and function and subclinical negative and positive symptoms in 22q11.2 deletion syndrome

Background

Identification of the early signs of schizophrenia would be a major achievement for the early intervention and prevention strategies in psychiatry. Social impairments are defining features of schizophrenia. Impairments of individual layers of social competencies are frequently described in individuals with 22q11.2 deletion syndrome (22q11.2DS), who have high risk of schizophrenia. It is unclear whether and to what extent social impairments associate with subclinical negative and positive symptoms in 22q11.2DS, and which layer of social impairments are more correlated with schizophrenia-related symptoms. The aims of this study were to conduct a comprehensive investigation of social impairments at three different levels (function, skill, and cognition) and their interrelationship and to determine to what degree the social impairments correlate to subclinical levels of negative and positive symptoms, respectively, in a young cohort of 22q11.2DS not diagnosed with schizophrenia.

Methods

The level of social impairment was addressed using questionnaires and objective measures of social functioning (The Adaptive Behavior Assessment System), skills (Social Responsiveness Scale), and cognition (The Awareness of Social Inference Test and CANTAB Emotional Recognition Task), and the presence of subclinical symptoms of schizophrenia were evaluated using the Structured Interview for Prodromal Syndromes in a cross-sectional case-control study of 29 cases and 29 controls, aged 12 to 25 years. Association between social impairment and negative and positive symptoms levels was examined in cases only.

Results

Subjects with 22q11.2DS were highly impaired in social function, social skills, and social cognition (p?≤?6.2?×?10^?9) relative to control peers and presented with more negative (p?=?5.8?×?10^?11) and positive (p?=?7.5?×?10^?4) symptoms. In particular, social functional and skill levels were highly associated with notably subclinical negative symptoms levels.

Conclusions

This study shows strong correlations between levels of social impairments and subclinical negative and positive symptoms. However, longitudinal studies are required to show if social impairments represent early disease manifestations. If parental or self-reporting suggests severe social impairment, it should advocate for clinical awareness not only to social deficits per se but also of potential subclinical psychosis symptoms.

     

Hippocampal volume reduction in chromosome 22q11.2 deletion syndrome (22q11.2DS): A longitudinal study of morphometry and symptomatology

Recent studies observed an association between the structural integrity of the hippocampal structure and the manifestations of clinically significant psychotic symptoms in participants at high risk for psychosis. The present study sought to investigate the longitudinal trajectory of the hippocampal volume and its subregions among a sample of participants affected by 22q11.2 deletion syndrome (22q11.2DS), a neurogenetic disorder associated with elevated risk for psychosis. We specifically investigated possible correlations between hippocampal volumes, as measured by magnetic resonance imaging (MRI), and the manifestation of positive psychotic symptoms (hallucinations and delusions). Regional hippocampal volumes were measured twice with cerebral MRI obtained at 3-year intervals in 30 healthy participants and 31 gender-matched 22q11.2 microdeletion carriers aged 6 to 22. We examined potential associations between psychotic symptom manifestations and volumetric parameters at both time points. We found a hippocampal body-driven significant reduction in hippocampal volume among patients with 22q11DS compared to controls. No significant group by time interaction for the total or the subregional volumes were observed. In patients, larger hippocampal head at baseline was associated with the presence of hallucinations at follow-up. We first discuss the reduced hippocampal body finding in light of potentially abnormal mesiocortical circuits. We further discuss the association between baseline hippocampal head volume in participants with 22q11DS as a possible marker related to the later unfolding of psychotic symptoms.     

Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS)

Background

Although significant impairments in the affective and cognitive facets of social cognition have been highlighted in patients with 22q11.2 deletion syndrome (22q11DS) in previous studies, these domains have never been investigated simultaneously within the same group of participants. Furthermore, despite theoretical evidence, associations between these two processes and schizotypal symptoms or social difficulties in this population have been scarcely examined.

Methods

Twenty-nine participants with 22q11DS and 27 typically developing controls (N = 5 siblings; N = 22 unrelated controls) aged between 11 and 21 years participated in the study. Both groups were matched for age and gender distribution. Two computerized social cognition tasks evaluating perspective and emotion recognition abilities were administered to all participants. The levels of schizotypal trait expression and social functioning were further investigated in both groups, based on a validated self-report questionnaire (Schizotypal Personality Questionnaire) and parental interview (Vineland Adaptive Behavior Scales).

Results

Participants with 22q11DS exhibited lower perspective-taking and emotion recognition capacities than typically developing controls. The two socio-cognitive dimensions investigated here were further correlated in healthy controls. The efficiency of perspective-taking processes (response time) was marginally related to the degree of schizotypal trait expression in patients with 22q11DS.

Conclusions

This study first provides support for significant deficits in two core facets of social cognition in 22q11DS. The associations observed between the experimental tasks and measures of social functioning or schizotypal symptoms in 22q11DS open promising research avenue, which should be more deeply investigated in future studies.

     

Atypical development of the executive attention network in children with chromosome 22q11.2 deletion syndrome

Impairment in the executive control of attention has been found in youth with chromosome 22q11.2 deletion syndrome (22q11.2DS). However, how this impairment is modified by other factors, particularly age, is unknown. Forty-six typically developing and 53 children with 22q11.2DS were tested with the attention networks task (ANT) in this cross-sectional study. We used logarithmic transform and linear modeling to assess age effects on the executive index of the ANT. Mixed modeling accounted for between subject variability, age, handedness, catecholamine-O-transferase (COMT; codon 158) genotype, and gender on performance for all experimental conditions (cue × flanker) and their two-level interactions. Children with 22q11.2DS showed a relative, age-dependent executive index impairment but not orienting or alerting network index impairments. In factorial analysis, age was a major predictor of overall performance. There was a significant effect of the 22q11.2DS on overall performance. Of note, children with 22q11.2DS are specifically vulnerable to incongruent flanker interference, especially at younger ages. We did not find an overall effect of COMT genotype or handedness. Children with 22q11.2DS demonstrated age-related impairment in the executive control of attention. Future investigation will likely reveal that there are different developmental trajectories of executive attentional function likely related to the development of schizophrenia in 22q11.2DS.