The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of attenuated psychotic symptoms, especially negative symptoms. Despite the deleterious impact of those symptoms on patients’ quality of life, little is known on the factors associated with their emergence in this population. In 22q11DS, previous studies investigated social cognition using eyetracking methods in order to advance understanding of negative symptoms. Results demonstrated an abnormal visual processing of socially relevant stimuli in this syndrome (Glaser et al., 2010). However, the processing of complex social scenes has never been explored. This might provide information about the way patients explore their social environment and help to better understand the differences underlying social impairments and negative symptoms.

A 102-second movie displaying a dyadic social interaction was presented to 106 22q11DS and 117 healthy controls. To measure the visual exploration in a longitudinal way, the sample will be divided in three age groups: between 6 and 12 years; between 12 and 18 years and participants > 19 years. Controls were used to create dynamic maps of typical exploration. These normative maps were obtained using a kernel density algorithm (Botev et al., 2010). Gaze patterns from each individual with 22q11DS were compared to the normative maps, allowing an unbiased quantifiable measure of social understanding.

Patients with 22q11DS showed a strongly significant deviance from the normative maps (F (1,164)=39.42, p<0.001), suggesting atypical processing and decreased interest for socially relevant stimuli. In patients with 22q11DS from the younger age group, there was a significant association between deviance values and age (r=0.332, p=0.028), indicating that adolescents with 22q11DS were generally less efficient at detecting socially-relevant information than their younger peers. In the older age group, deviance values were associated with the severity of negative symptoms (r=0.322, p=0.014) but were unrelated to age, intellectual functioning or positive symptoms.

This study reveals abnormal visual exploration patterns during the processing of complex social scenes in 22q11DS, which are related to the presence of negative symptoms. Longitudinal explorations using this technique will provide a tool for quantifying social impairments and will determine whether atypical gaze patterns are predictive for the onset of significant negative symptoms and/or psychosis.

Objective: 22q11.2 Deletion Syndrome (22q11.2DS) is associated with increased risk for schizophrenia in adulthood while ADHD is the most prevalent diagnosis in childhood. ADHD inattention symptoms are pronounced in 22q11.2DS and given that attentional impairment is a core feature of schizophrenia, we examined whether ADHD inattention symptoms are associated with psychosis in 22q11.2DS. To further investigate whether these symptoms are associated with genetic liability to psychosis in 22q11.2DS, we also directly compared the prevalence of ADHD symptoms with other non-deleted (ND) groups with increased risk for psychosis.
Methods: 137 individuals with 22q11.2DS (mean age: 14.0), 84 ND individuals with psychosis-spectrum (mean age: 16.9) and 31 ND individuals with family history of psychosis (mean age: 17.0) were included in the study. Psychopathology was assessed using research diagnostic assessments.
Results: ADHD symptoms, including inattention and hyperactivity, were associated with psychosis spectrum (p=0.004 and p=0.01 respectively), while ADHD inattention symptoms were also associated with positive (p=0.004), negative (p=0.03), disorganized/general symptoms (p=0.01) and ADHD hyperactivity symptoms were associated with disorganized/general symptoms (p=0.04). The prevalence of ADHD inattention symptoms was higher in 22q11.2DS and psychosis spectrum in relation to ND individuals with psychosis spectrum (p<0.001), even when adjusting for cognitive impairment. The pattern was similar when comparing individuals with 22q11.2DS and ND individuals with family history of psychosis.
Conclusions: This is the first study to examine the associations between ADHD and psychosis in 22q11.2DS. Our findings support a potentially important role of ADHD inattention symptoms in the development of psychosis in 22q11.2DS and potentially beyond. Further results using data from the IBBC consortium will be presented.

Objectives: Long-term memory (as opposed to short-term) is the ability to store and recall information for a long period and is characterized by structural and functional changes of the neural networks of the brain. A phenomenon that often goes undetected is whether the forgetting pace of the information is accelerated when compared to a control population. Indeed, most standardized memory assessments measure delays up to 30-40 minutes and therefore are not very representative of daily life performance (e.g. academic learning). 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder associated with a specific cognitive profile and high risk for schizophrenia. From previous research and patient’s family reports in daily life, long-term memory processes seem to be altered in this population. More specifically a superiority of verbal memory processes over visual memory processes have been reported in several papers. To our knowledge, no previous research has investigated accelerated long term forgetting in this population differentiating between verbal and visual processes.
Methods: we investigated verbal and visual long-term memory using a modified version of Rey’s 15 words/15 signs. Eighty-three participants (44 with 22q11.2DS) aged between 8 and 24 years learned a series of words and signs and were asked to recall them freely after 4 different delays in time (thirty minutes, one day, one week and one month). Performance was compared between groups (22q11.2DS vs Controls) and modality (verbal vs. visual) at each time delay, controlling for age.
Results: Firstly, in the control group we found a positive correlation of performances with age at every time delay (p < 0.031), indicating that as individuals are older, they remember more information. Interestingly this advantage of age was not present in the 22q11.2DS group, at any time delay. Secondly, comparing the percentage of forgetting at each time delay showed that accelerated forgetting started earlier in the verbal task (after one day) than in the non-verbal task (after one week) in patients with 22q11.2DS.
Conclusion: There was no advantage of age on performance in the 22q11.2DS group. We showed an accelerated forgetting phenomenon in 22q11.2DS and different forgetting curves depending on modality.

Introduction: 22q11.2 deletion syndrome (22q) is a complex genetically determined microdeletion syndrome with prevalence estimates of 1 in 2000-4000 live births. Common neuroanatomical features of 22q include alteration to multiple brain regions. Sensorimotor and visual cognitive processes reliant on connectivity between distributed brain regions may be affected in 22q. Visual information processing impairment represents a core feature of schizophrenia. 22q is one of the strongest genetic risk factors for developing schizophrenia. Studies in schizophrenia show impairments in sensorimotor systems involved in the initiation and early integration of visual feedback as well as impaired pursuit maintenance and similar impairment is seen in their first-degree relatives. The present study examined several aspects of oculomotor processing in 22q. We hypothesized that individuals with 22q would generally show difficulty initiating and maintaining pursuit commands relative to typically developing controls (TD).
Method: 22q (n=19, mean age 16.9 +/- 2.8 years, 7 males) and typically developing adolescents (TD) (n=20, mean age 16.7, +/- 3.8 years, 10 males) completed prosaccade and smooth pursuit eye movement (SPEM) tasks. Saccade latency and accuracy were recorded as indicators of performance in the prosaccade task and SPEM gain, saccade type and frequency were calculated as indicators of SPEM performance.
Results: The groups showed comparable prosaccade accuracy (22q = 94% vs TD = 96%). The 22q group showed lower mean latency compared to the TD group (p= 0.009) remaining significant when only accurate trials were examined (p< 0.001,). Group comparisons indicated gain maintenance differences (p= 0.001) and 22q participants also showed increased frequency of all saccadic subtypes (p=0.02).
Conclusions: We report impaired pursuit maintenance among adolescents with 22q without psychosis compared to TD controls. These may indicate impaired integration of higher-order predictive processes, though further examination of sensorimotor components of pursuit eye movement is warranted. Reduced mean latency of saccadic responses may reflect reduced inhibition of saccadic eye movements.

Norm charts play an important role in daily clinical care. They can provide insight into the degree of deviation for individual trajectories. For several genetic syndromes normative trajectories for morphological aspects have been constructed. These syndrome-specific norm charts facilitate both clinical care and research.
Similar to morphological features, it is now becoming increasingly clear that certain genetic disorders can also manifest characteristic trajectories of cognitive development. However, to date there are no syndrome-specific charts for cognitive development. Using data of the largest study to date involving individuals with the 22q11.2 deletion syndrome (22q11DS), we created a norm chart for cognitive development. The chart showed a decline in IQ and this norm chart allowed the identification of an association between a decline in verbal IQ and the subsequent development of schizophrenia. Providing a comprehensive norm chart for IQ in 22q11DS in a larger dataset will enable validation of this finding, and will be important for both clinical care and research of this condition.
The aim of this study is to produce a cognitive development norm chart for 22q11DS between age 6 and 40 years, which can be used for both clinical and research purposes.
We made use of the IBBC database with 1871 participants with 22q11DS. We used all available IQ data points to construct norm charts (for FSIQ, VIQ and PIQ), after a comprehensive quality control procedure to ensure reliable and comparable IQ data across all international sites. We extended the age-range examined (ages 6 to 40 years). We compared several procedures (polynomial - and Linear Quantile Regression) used to construct IQ norm charts in order to identify the optimal method for the data available.
All norm chart methods showed a similar IQ decline as in the initial finding. The norm chart produced by polynomial regression provided the best fit with the data. The final norm chart performed well across the entire age-range.
This is the first time a norm chart has been constructed for neurocognitive functioning in a specific genetic syndrome. We validated our previous finding that IQ in 22q11DS shows a decline over development. This research has provided an IQ norm chart that can be applied both in clinical care and research. We conclude that a disorder-specific neurocognitive developmental norm chart is feasible, given the availability of a sufficient number of standardized IQ measures.

Background
22q11.2 deletion syndrome (22q11DS) is a genetic disorder associated with an increased risk for psychosis. A dysfunctional motivational reward system is thought to be one of the salient features in psychosis caused by abnormal dopamine functioning. It is unknown whether patients with 22q11DS have a dysfunctional reward system.

Methods
We included 12 adults with 22q11DS (age: 34,6 years, 67% females) and 16 healthy controls (HC, age:38,1 years, 75% females). A single infusion DA D2/3 receptor [18F]fallypride positron emission tomography (PET) scan was acquired to investigate the DAergic activity in striatal (putamen, caudate nucleus, ventral striatum) and frontal regions. During the PET scan all subjects performed a version of the learning phase of the Probabilistic Stimulus Selection Task for reward learning (RL), modified to deliver social feedback.

Results
IQ-scores were significantly lower in the 22q11DS group (p<.001) compared to HC. The 22q11DS group earned significantly less money (p <.05) and performed worse during the RL-task (p<.05) than HC. The preliminary PET analyses show that the percentage of active voxels during reward learning is significantly higher in 22q11DS compared to HC in the right caudate nucleus (p <.05).

Conclusions
These results indicate that people with 22q11DS are less susceptible for reward than HC because their overall performance during RL is worse than HC. In addition, people with 22q11DS showed different special extent of reward-induced DA release in striatal regions compared to HC. The lower reward sensitivity could be a result of haplo-insufficiency of COMT in 22q11DS and consequently abnormal dopamine functioning.