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.

Negative and paranoid symptoms are associated with negative performance beliefs and social cognition in 22q11.2 deletion syndrome.

AIMS: 22q11.2 deletion syndrome (22q11.2DS) is a neurogenetic condition associated with an increased risk of developing schizophrenia. Previous studies have shown that negative symptoms represent the most specific clinical characteristic of psychosis in 22q11.2DS and are strongly associated with outcome. However, the psychological mechanisms associated with these symptoms in this population are poorly understood. In accordance with recent conceptualizations in the field of schizophrenia, the present study aims at investigating whether negative symptoms are associated with the presence of negative performance beliefs and cognitive deficits. METHODS: Thirty-five participants with 22q11.2DS and 24 typically developing individuals aged between 11 and 24 years were included in the study. Self-reported schizotypal symptoms (cognitive-perceptual, paranoid, negative and disorganization symptoms) and dysfunctional beliefs (negative performance beliefs and need for approval) were assessed. Measures of processing speed, verbal memory, working memory, executive functioning and face recognition were also extracted from a broad cognitive evaluation protocol. RESULTS: Adolescents with 22q11.2DS reported significantly higher score on the negative dimension of the Schizotypal Personality Questionnaire than controls, even when controlling for the influence of anxiety/depression and intellectual functioning. Negative and paranoid symptoms were associated with the severity of negative performance beliefs and lower face recognition abilities. Mediation analyses revealed that negative performance beliefs significantly mediated the association between face recognition and negative/paranoid symptoms. CONCLUSIONS: These findings suggest that negative performance beliefs and basic social cognitive mechanisms are associated with negative and paranoid symptoms in individuals with 22q11.2DS. Implications for intervention are discussed in this article.

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.

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.

Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with cognitive and functional impairments and increased risk for schizophrenia. We characterized multitasking abilities of adolescents with 22q11.2DS using an experimental naturalistic setting and examined whether multitasking impairments were associated with real-world functioning and negative symptoms. Thirty-nine adolescents (19 with 22q11.2DS and 20 controls) underwent the Multitasking Evaluation for Adolescents. Real-world functioning and clinical symptoms were assessed in participants with 22q11.2DS. Adolescents with 22q11.2DS performed poorly in the multitasking evaluation. Our data also suggest that multitasking abilities are related to adaptive functioning in the practical domain and negative symptoms. This study shows that adolescents with 22q11.2DS are characterized by multitasking impairments, which may be relevant for several aspects of the clinical phenotype.

Schizophrenia patients and 22q11.2 deletion syndrome adolescents at risk express the same deviant patterns of resting state EEG microstates: A candidate endophenotype of schizophrenia.

Schizophrenia is a complex psychiatric disorder and many of the factors contributing to its pathogenesis are poorly understood. In addition, identifying reliable neurophysiological markers would improve diagnosis and early identification of this disease. The 22q11.2 deletion syndrome (22q11DS) is one major risk factor for schizophrenia. Here, we show further evidence that deviant temporal dynamics of EEG microstates are a potential neurophysiological marker by showing that the resting state patterns of 22q11DS are similar to those found in schizophrenia patients. The EEG microstates are recurrent topographic distributions of the ongoing scalp potential fields with temporal stability of around 80 ms that are mapping the fast reconfiguration of resting state networks. Five minutes of high-density EEG recordings was analysed from 27 adult chronic schizophrenia patients, 27 adult controls, 30 adolescents with 22q11DS, and 28 adolescent controls. In both patient groups we found increased class C, but decreased class D presence and high transition probabilities towards the class C microstates. Moreover, these aberrant temporal dynamics in the two patient groups were also expressed by perturbations of the long-range dependency of the EEG microstates. These findings point to a deficient function of the salience and attention resting state networks in schizophrenia and 22q11DS as class C and class D microstates were previously associated with these networks, respectively. These findings elucidate similarities between individuals at risk and schizophrenia patients and support the notion that abnormal temporal patterns of EEG microstates might constitute a marker for developing schizophrenia.

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.