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

BackgroundAlterations of the reward system have been proposed as one of the core mechanisms underlying the expression of negative symptoms in schizophrenia. Specifically, deficits in specific reward components and white matter (WM) integrity of the reward system have been highlighted. The putative link between negative symptoms and the hedonic experience, or structural connectivity of the reward system has never been examined in the 22q11.2 deletion syndrome (22q11DS), a condition with increased risk for psychosis.MethodAnticipatory and consummatory dimensions of pleasure were assessed in participants with 22q11DS (N = 54) and healthy controls (N = 55). In patients with 22q11DS, the association between pleasure scores and positive or negative symptoms was investigated. Furthermore, WM integrity of the accumbofrontal tract was quantified using diffusion tensor imaging (DTI). Associations between DTI measures, pleasure dimensions and negative symptoms were examined.ResultsPatients with 22q11DS showed reduced anticipatory and consummatory pleasure compared to controls. Furthermore, anticipatory pleasure scores were negatively correlated to negative and positive symptoms in 22q11DS. WM microstructural changes of the accumbofrontal tract in terms of increased fractional anisotropy and reduced radial anisotropy were also identified in patients. However, no significant correlation between the DTI measures and pleasure dimensions or psychotic symptoms was observed.ConclusionsThis study revealed that participants with 22q11DS differed in their experience of pleasure compared to controls. The anticipatory pleasure component appears to be related to negative and positive symptom severity in patients. Alterations of WM integrity of the accumbofrontal tract seem to be related to myelination abnormalities in 22q11DS patients.

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Ultra High Risk Status and Transition to Psychosis in 22q11.2 Deletion Syndrome

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.258 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S81-S82

Author(s):

M. Armando ◽

M. Schneider ◽

M. Pontillo ◽

S. Vicari ◽

M. Debbane ◽

...

Keyword(s):

High Risk ◽

Predictive Value ◽

Transition Rate ◽

22Q11.2 Deletion Syndrome ◽

Human Model ◽

Deletion Syndrome ◽

Additional Contribution ◽

22Q11.2 Deletion ◽

Level Of Functioning ◽

Ultra High Risk

The 22q11.2 deletion syndrome (22q11DS) is characterized by high rates of psychotic symptoms and schizophrenia, making this condition a promising human model for studying risk factors for psychosis. We explored the predictive value of ultra high-risk (UHR) criteria in a sample of patients with 22q11DS. We also examined the additional contribution of sociodemographic, clinical and cognitive variables to predict transition to psychosis within a mean interval of 32.56176 months after initial assessment. Eighty-nine participants with 22q11DS (age range: 8–30 years; mean: 16.1647) were assessed using the structured interview for psychosis-risk syndromes. Information on axis I diagnoses, internalizing and externalizing symptoms, level of functioning and IQ was also collected. At baseline, 22 (24.7%) participants met UHR criteria. Compared to those without a UHR condition, they had a significantly lower functioning, more frequent anxiety disorders and more severe psychopathology. Transition rate to psychosis was 27.3% in UHR and 4.5% in non-UHR participants. Cox regression analyses revealed that UHR status significantly predicted conversion to psychosis. Baseline level of functioning was the only other additional predictor. This is the first study investigating the predictive value of UHR criteria in 22q11DS. It indicates that the clinical path leading to psychosis is broadly comparable to that observed in other clinical high-risk samples. Nevertheless, the relatively high transition rate in non-UHR individuals suggests that other risk markers should be explored in this population. The role of low functioning as a predictor of transition to psychosis should also be investigated more in depth.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Implications of COMT and Subclinical Psychiatric Symptoms on the Phenotypic Variability of 22q11.2 Deletion Syndrome: A Transversal and Longitudinal Approach

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.261 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S82-S83

Author(s):

S. Guerrera ◽

M. Armando ◽

M. Pontillo ◽

F. Papaleo ◽

S. Vicari

Keyword(s):

Negative Symptoms ◽

Psychiatric Symptoms ◽

Phenotypic Variability ◽

22Q11.2 Deletion Syndrome ◽

Structured Interview ◽

Deletion Syndrome ◽

Psychotic Symptoms ◽

22Q11.2 Deletion ◽

Comt Polymorphism ◽

The Impact

Introduction22q11.2 deletion syndrome (22q11.2DS) results from a hemizygous microdeletion on chromosome 22 and is characterized by phenotypic variability. Several studies have been conducted on the impact of COMT functional polymorphism in 22q11DS, suggesting that attenuated psychotic manifestations are frequent in children and adolescents and represent one of the strongest predictors for the onset of psychotic disorder.ObjectivesWe explored possible interaction between COMT polymorphism and subclinical psychiatric symptoms in a 22q11.2DS cohort of 42 participants aged 6 to 26 years: 17 hemizygosity for COMT-Met and 25 hemizygosity for COMT-Val.AimsTo analyse impact of COMT gene in 22q11DS and its related psychiatric correlates.MethodEach participant, genotyped for the catechol O-methyltransferase (COMT) Met/Val polymorphism, underwent structured psychiatric and cognitive assessment. Analysis of positive and negative symptoms was performed by the structured interview for prodromal syndromes (SIPS). Finally, longitudinal data available in a subsample of 24 individuals were used to explore the developmental trajectories of psychotic symptoms one year later.ResultsThere was a significant positive correlation between COMT Val polymorphism and positive symptoms; at follow-up, no significant correlation were found between COMT polymorphism and psychiatric symptoms. No other significant differences were found between groups (Comt/Met-Comt/Val) on any other CBCL or QI score.ConclusionsCOMT and additional genes microdeleted might interact in the susceptibility to schizophrenia in 22q11.2DS: psychotic symptoms might result from an epistatic interaction with other genes. Moreover, gene-environment, in presence of genetic vulnerability could increase the risk of schizophrenia in 22q11DS.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Two Novel Mouse Models Mimicking Minor Deletions in 22q11.2 Deletion Syndrome Revealed the Contribution of Each Deleted Region to Psychiatric Disorders

10.21203/rs.3.rs-137341/v1 ◽

2020 ◽

Author(s):

Ryo Saito ◽

Chika Miyoshi ◽

Michinori Koebis ◽

Itaru Kushima ◽

Kazuki Nakao ◽

...

Keyword(s):

Locomotor Activity ◽

Psychiatric Disorders ◽

Mouse Models ◽

Prepulse Inhibition ◽

Animal Studies ◽

Negative Symptoms ◽

22Q11.2 Deletion Syndrome ◽

Social Recognition ◽

Deletion Syndrome ◽

22Q11.2 Deletion

Abstract 22q11.2 deletion syndrome (22q11.2DS) is a disorder caused by the segmental deletion of human chromosome 22. This chromosomal deletion is known as high genetic risk factors for various psychiatric disorders. The different deletion types are identified in 22q11.2DS patients, including the most common 3.0-Mb deletion, and the less-frequent 1.5-Mb and 1.4-Mb deletions. In previous animal studies of psychiatric disorders associated with 22q11.2DS mainly focused on the 1.5-Mb deletion and model mice mimicking the human 1.5-Mb deletion have been established with diverse genetic backgrounds, which resulted in the contradictory phenotypes. On the other hand, the contribution of the genes in 1.4-Mb region to psychiatric disorders is poorly understood. In this study, we generated two mouse lines that reproduced the 1.4-Mb and 1.5-Mb deletions of 22q11.2DS [Del(1.4Mb)/+ and Del(1.5Mb)/+] on the pure C57BL/6N genetic background. These mutant mice were analyzed comprehensively by behavioral tests, such as measurement of locomotor activity, sociability, prepulse inhibition and fear-conditioning memory. Del(1.4Mb)/+ mice displayed decreased locomotor activity, which possibly reproduces the negative symptoms of schizophrenia. Del(1.5Mb)/+ mice showed reduction of prepulse inhibition and impairment of contextual- and cued-dependent fear memory, which is consistent with previous reports. Furthermore, apparently intact social recognition in Del(1.4Mb)/+ and Del(1.5Mb)/+ mice suggests that the impaired social recognition requires mutations both in 1.4-Mb and 1.5 Mb regions. Our previous study has shown that Del(3.0Mb)/+ mice mimicking the human 3.0-Mb deletion presented disturbance of behavioral circadian rhythm. Therefore, we further evaluated sleep/wakefulness cycles in Del(3.0Mb)/+ mice by electroencephalogram (EEG) and electromyogram (EMG) recording. EEG/EMG analysis revealed the disturbed wakefulness and non-rapid eye moving sleep (NREMS) cycles in Del(3.0Mb)/+ mice, suggesting that Del(3.0Mb)/+ mice may be unable to maintain their wakefulness. Together, our mouse models deepen our understanding of genetic contributions to schizophrenic phenotypes related to 22q11.2DS.

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

American Journal on Intellectual and Developmental Disabilities ◽

10.1352/1944-7558-121.2.151 ◽

2016 ◽

Vol 121 (2) ◽

pp. 151-164 ◽

Cited By ~ 3

Author(s):

Maude Schneider ◽

Stephan Eliez ◽

Julie Birr ◽

Sarah Menghetti ◽

Martin Debbané ◽

...

Keyword(s):

Real World ◽

Negative Symptoms ◽

Adaptive Functioning ◽

Clinical Symptoms ◽

22Q11.2 Deletion Syndrome ◽

Deletion Syndrome ◽

Functional Impairments ◽

22Q11.2 Deletion ◽

Increased Risk ◽

Naturalistic Setting

Abstract 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.

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