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Swiss VCFS Cohort: a 10-year longitudinal investigation from genes to brain to cognition for understanding psychosis proneness in 22q11.2 deletion

English title Swiss VCFS Cohort: a 10-year longitudinal investigation from genes to brain to cognition for understanding psychosis proneness in 22q11.2 deletion
Applicant Eliez Stephan
Number 144260
Funding scheme Project funding (special)
Research institution Service Médico-Pédagogique Département de Psychiatrie Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurology, Psychiatry
Start/End 01.04.2013 - 31.12.2017
Approved amount 558'790.00
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Keywords (1)

VCFSNeuroimaging, Brain, Longitudinal study, Neuro

Lay Summary (French)

Lead
Les participants à l'étude longitudinale sur la microdélétion 22q11.2 sont vus selon un protocole incluant l'IRM. Ces données permettent l'étude des interactions entre marqueurs génétiques, changements cérébraux, cognition et comportement, chez des personnes affectées et des contrôles sains. Nos résultats prédisent les trajectoires du développement cérébral chez les personnes affectées et fournissent des critères pour la compréhension et le traitement de la psychose dans la population générale.
Lay summary

Le syndrome vélo-cardio-facial ou microdélétion 22q11.2 est une maladie génétique due à une microdélétion sur le chromosome 22. 60 gènes sont codés dans la région délétée. Certains de ces gènes sont considérés comme responsables des changements cérébraux et comportementaux associés au syndrome. L'impact de ces changements a un effet sur le développement. Ainsi, la fréquence de la psychose est élevée, puisqu'elle affecte 30% de ces adolescents et adultes. Par conséquent, ce syndrome représente une occasion unique de comprendre le lien existant entre gènes, structure et fonction du cerveau d'une part, et comportement d'autre part, tout au long du développement. La Suisse a la chance d'avoir mis au point et suivi, depuis 2001, l'une des deux ou trois cohortes longitudinales les mieux documentées au monde. Les participants à la recherche sont évalués à intervalles réguliers, à l'aide de tâches cognitives standardisées et expérimentales, eye tracking, questionnaires de comportement, évaluation psychiatrique standard, ainsi que mesures cérébrales structurelles et fonctionnelles. Le suivi longitudinal de la cohorte suisse permet aussi de comparer des personnes affectées par ce syndrome qui développent une psychose, avec celles pour qui ce n'est pas le cas. Cela nous permet d'identifier les traits prodromiques qui précèdent la psychose, et d'isoler les facteurs qui mettent un patient à risque élevé de problèmes psychiatriques ultérieurs. Par conséquent, nos résultats permettent de prédire les trajectoires de développement cérébral des personnes affectées par une microdélétion 22q11.2 et de fournir des critères pour les cliniciens. Ceux-ci peuvent être utilisés pour surveiller et prévenir la psychose, de l'enfance à l'âge adulte, chez les personnes qui sont affectées de ce syndrome. Ces découvertes aident aussi à la compréhension et au traitement des personnes, dans la population générale, qui sont à risque de développer une psychose.

Direct link to Lay Summary Last update: 25.01.2013

Lay Summary (English)

Lead
Participants in our 12-year longitudinal study of 22q11.2DS are seen at fixed intervals using a protocol including MRI. These data permit the study of interactions between genetic markers, brain changes, cognition and behavior in 22q11DS vs. healthy controls, and in patients with and without psychosis. Our findings predict neurodevelopmental trajectories in individuals with 22q11DS, and provide criteria that can be used for monitoring and preventing psychosis in the general population.
Lay summary
Velo-cardio-facial syndrome or 22q11.2 deletion syndrome is a genetic disorder caused by a microdeletion on chromosome 22. Sixty genes are encoded in the deleted region, some of which are highly expressed in the brain and considered responsible for the cerebral and behavioural changes associated with the syndrome. The impact of these changes snowballs with development, and it is a high frequency of psychosis, especially schizophrenia, in 30% of affected individuals that continues to confound both researchers and clinicians. Indeed, 22q11.2 deletion syndrome represents a unique opportunity to understand the association between genes, brain structure and function, and behaviour throughout development. Switzerland is fortunate to have developed and followed one of only two or three thoroughly documented longitudinal cohorts in the world since 2001. Research participants are evaluated at fixed intervals using both standardized and experimental cognitive tasks, eye tracking, behavioural questionnaires, standardized psychiatric interviews, as well as multiple benchmarks of brain structure and function. The resulting longitudinal dataset enables us to measure neurodevelopmental patterns over time; to study the association between genetic markers, structural brain changes from childhood to adulthood, and differences in cerebral connectivity over time; and to understand how these differences affect brain function, cognition and ultimately behavior. Longitudinal monitoring of the Swiss cohort also allows us to compare individuals affected by the syndrome who develop psychosis, with those who don’t. This enables us to identify prodromal traits that precede psychosis, and makes it possible to isolate the factors that put a patient at high-risk for subsequent psychiatric problems. Consequently, our findings help to predict the neurodevelopmental trajectories of individuals with 22q11.2 deletion syndrome, and provide criteria to clinicians that can be used for monitoring and preventing psychosis in affected individuals, from early childhood to adulthood. These same discoveries inform understanding and treatment of individuals in the general population who are at risk for psychosis.
Direct link to Lay Summary Last update: 25.01.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis.
Padula Maria Carmela, Schaer Marie, Armando Marco, Sandini Corrado, Zöller Daniela, Scariati Elisa, Schneider Maude, Eliez Stephan (2018), Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis., in Psychological medicine, 1-9.
Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome.
Padula Maria C, Scariati Elisa, Schaer Marie, Sandini Corrado, Ottet Marie Christine, Schneider Maude, Van De Ville Dimitri, Eliez Stephan (2017), Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome., in NeuroImage. Clinical, 16, 142-150.
Does differential visual exploration contribute to visual memory impairments in 22q11.2 microdeletion syndrome?
Bostelmann M, Glaser B, Zaharia A, Eliez S, Schneider M (2017), Does differential visual exploration contribute to visual memory impairments in 22q11.2 microdeletion syndrome?, in Journal of intellectual disability research : JIDR, 61(12), 1174-1184.
Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS)
Badoud D., Schneider M., Menghetti S., Glaser B., Debbané M., Eliez S. (2017), Understanding others: a pilot investigation of cognitive and affective facets of social cognition in patients with 22q11.2 deletion syndrome (22q11DS), in Journal of Neurodevelopmental Disorders, 9(1), 35-35.
A neurogenetic model for the study of schizophrenia spectrum disorders: The International 22q11.2 Deletion Syndrome Brain Behavior Consortium
Gur R. E., Bassett A. S., McDonald-Mcginn D. M., Bearden C. E., Chow E., Emanuel B. S., Owen M., Swillen A., Van Den Bree M., Vermeesch J., Vorstman J. A.S., Warren S., Lehner T., Morrow B. (2017), A neurogenetic model for the study of schizophrenia spectrum disorders: The International 22q11.2 Deletion Syndrome Brain Behavior Consortium, in Molecular Psychiatry, 22(12), 1664-1672.
Time-based prospective memory in children and adolescents with 22q11.2 deletion syndrome.
Souchay Céline, Dubourg Lydia, Ballhausen Nicola, Schneider Maude, Cerf Charline, Schnitzspahn Katharina, Faivre Laurence, Kliegel Matthias, Eliez Stephan (2017), Time-based prospective memory in children and adolescents with 22q11.2 deletion syndrome., in The Clinical neuropsychologist, 1-12.
Quantifying indices of short- and long-range white matter connectivity at each cortical vertex
Padula Maria Carmela, Schaer Marie, Scariati Elisa, Mutlu A. Kadir, Zöller Daniela, Zöller Daniela, Schneider Maude, Eliez Stephan, Eliez Stephan (2017), Quantifying indices of short- and long-range white matter connectivity at each cortical vertex, in PLoS ONE, 12(11), e0187493.
Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the GPR98 Locus on 5q14.3.
Guo Tingwei, Repetto Gabriela M, McDonald McGinn Donna M, Chung Jonathan H, Nomaru Hiroko, Campbell Christopher L, Blonska Anna, Bassett Anne S, Chow Eva W C, Mlynarski Elisabeth E, Swillen Ann, Vermeesch Joris, Devriendt Koen, Gothelf Doron, Carmel Miri, Michaelovsky Elena, Schneider Maude, Eliez Stephan, Antonarakis Stylianos E, Coleman Karlene, Tomita-Mitchell Aoy, Mitchell Michael E, Digilio M Cristina, Dallapiccola Bruno, Marino Bruno, Philip Nicole, Busa Tiffany, Kushan-Wells Leila, Bearden Carrie E, Piotrowicz Małgorzata, Hawuła Wanda, Roberts Amy E, Tassone Flora, Simon Tony J, van Duin Esther D A, van Amelsvoort Thérèse A, Kates Wendy R, Zackai Elaine, Johnston H Richard, Cutler David J, Agopian A J, Goldmuntz Elizabeth, Mitchell Laura E, Wang Tao, Emanuel Beverly S, Morrow Bernice E, Morrow Bernice E (2017), Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the GPR98 Locus on 5q14.3., in Circulation. Cardiovascular genetics, 10(5), e001690.
Morphological brain changes associated with negative symptoms in patients with 22q11.2 Deletion Syndrome.
Mihailov Angeline, Padula Maria Carmela, Scariati Elisa, Schaer Marie, Schneider Maude, Eliez Stephan (2017), Morphological brain changes associated with negative symptoms in patients with 22q11.2 Deletion Syndrome., in Schizophrenia research, 188, 52-58.
Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study.
Weisman Omri, Guri Yael, Gur Raquel E, McDonald-McGinn Donna M, Calkins Monica E, Tang Sunny X, Emanuel Beverly, Zackai Elaine H, Eliez Stephan, Schneider Maude, Schaer Marie, Kates Wendy R, Antshel Kevin M, Fremont Wanda, Shashi Vandana, Hooper Stephen R, Armando Marco, Vicari Stefano, Pontillo Maria, Kushan Leila, Jalbrzikowski Maria, Bearden Carrie E, Cubells Joseph F, Ousley Opal Y, Walker Elaine F, Simon Tony J, Stoddard Joel, Niendam Tara A, van den Bree Marianne B M, Gothelf Doron, Gothelf Doron (2017), Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study., in Schizophrenia bulletin, 43(5), 1079-1089.
Psychotic symptoms influence the development of anterior cingulate BOLD variability in 22q11.2 deletion syndrome.
Zöller Daniela, Padula Maria Carmela, Sandini Corrado, Schneider Maude, Scariati Elisa, Van De Ville Dimitri, Schaer Marie, Eliez Stephan (2017), Psychotic symptoms influence the development of anterior cingulate BOLD variability in 22q11.2 deletion syndrome., in Schizophrenia research, S0920-9964.
Implication of reward alterations in the expression of negative symptoms in 22q11.2 deletion syndrome: a behavioural and DTI study.
Dubourg L, Schneider M, Padula M C, Chambaz L, Schaer M, Eliez S (2017), Implication of reward alterations in the expression of negative symptoms in 22q11.2 deletion syndrome: a behavioural and DTI study., in Psychological medicine, 47(8), 1442-1453.
Negative and paranoid symptoms are associated with negative performance beliefs and social cognition in 22q11.2 deletion syndrome.
Schneider Maude, Van der Linden Martial, Menghetti Sarah, Debbané Martin, Eliez Stephan (2017), Negative and paranoid symptoms are associated with negative performance beliefs and social cognition in 22q11.2 deletion syndrome., in Early intervention in psychiatry, 11(2), 156-164.
Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions.
Padula Maria C, Schaer Marie, Scariati Elisa, Maeder Johanna, Schneider Maude, Eliez Stephan (2017), Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions., in Human brain mapping, 38(4), 2177-2189.
No age effect in the prevalence and clinical significance of ultra-high risk symptoms and criteria for psychosis in 22q11 deletion syndrome: Confirmation of the genetically driven risk for psychosis?
Armando Marco, Schneider Maude, Pontillo Maria, Vicari Stefano, Debbané Martin, Schultze-Lutter Frauke, Eliez Stephan (2017), No age effect in the prevalence and clinical significance of ultra-high risk symptoms and criteria for psychosis in 22q11 deletion syndrome: Confirmation of the genetically driven risk for psychosis?, in PLOS ONE, 12(4), e0174797-e0174797.
Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome.
Zöller Daniela, Schaer Marie, Scariati Elisa, Padula Maria Carmela, Eliez Stephan, Van De Ville Dimitri (2017), Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome., in NeuroImage, 149, 85-97.
No evidence for the presence of genetic variants predisposing to psychotic disorders on the non-deleted 22q11.2 allele of VCFS patients.
Guipponi M, Santoni F, Schneider M, Gehrig C, Bustillo X B, Kates W R, Morrow B, Armando M, Vicari S, Sloan-Béna F, Gagnebin M, Shashi V, Hooper S R, Eliez S, Antonarakis S E (2017), No evidence for the presence of genetic variants predisposing to psychotic disorders on the non-deleted 22q11.2 allele of VCFS patients., in Translational psychiatry, 7(2), 1039-1039.
Adolescence is the turning point of sex-dichotomous COMT genetic effects
Sannino Sarah, Padula Maria Carmela, Manago F, Schaer Marie, Schneider Maude, Armando Marco, Scariati Elisa, Sloan-Bena Frédérique, Mereu M, Pontillo Maria, Vicari Stefano, Contarini G, Chiabrera C, Pagani M, Gozzi A, Eliez Stephan, Papaleo Francesco (2017), Adolescence is the turning point of sex-dichotomous COMT genetic effects, in Translational Psychiatry , 7(5), e1141.
Détection et traitement précoce des sujets à haut risque clinique de psychose : définitions et recommandations
Michel Chantal, Schmidt S, Toffel Elodie, Eliez Stephan, Solida-Tozzi Alexandra, Armando Marco, Schultze-Lutter Frauke, Debbané Martin (2017), Détection et traitement précoce des sujets à haut risque clinique de psychose : définitions et recommandations, in Encéphale, 43(3), 292.
An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome.
Váša František, Griffa Alessandra, Scariati Elisa, Schaer Marie, Urben Sébastien, Eliez Stephan, Hagmann Patric (2016), An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome., in NeuroImage. Clinical, 10, 239-49.
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.
Bostelmann Mathilde, Schneider Maude, Padula Maria Carmela, Maeder Johanna, Schaer Marie, Scariati Elisa, Debbané Martin, Glaser Bronwyn, Menghetti Sarah, Eliez Stephan (2016), 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., in Journal of neurodevelopmental disorders, 8, 41-41.
Developmental trajectories of executive functions in 22q11.2 deletion syndrome
Maeder Johanna, Schneider Maude, Bostelmann Mathilde, Debbané Martin, Glaser Bronwyn, Menghetti Sarah, Schaer Marie, Eliez Stephan (2016), Developmental trajectories of executive functions in 22q11.2 deletion syndrome, in Journal of Neurodevelopmental Disorders, 8(1), 10-10.
Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis.
Scariati Elisa, Schaer Marie, Karahanoglu Isik, Schneider Maude, Richiardi Jonas, Debbané Martin, Van De Ville Dimitri, Eliez Stephan (2016), Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis., in Cortex; a journal devoted to the study of the nervous system and behavior, 82, 86-99.
Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome.
Schneider Maude, Armando Marco, Pontillo Maria, Vicari Stefano, Debbané Martin, Schultze-Lutter Frauke, Eliez Stephan (2016), Ultra high risk status and transition to psychosis in 22q11.2 deletion syndrome., in World psychiatry : official journal of the World Psychiatric Association (WPA), 15(3), 259-265.
Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome.
Scariati E, Padula M C, Schaer M, Eliez S (2016), Long-range dysconnectivity in frontal and midline structures is associated to psychosis in 22q11.2 deletion syndrome., in Journal of neural transmission (Vienna, Austria : 1996), 123(8), 823-39.
Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis.
Fonseca-Pedrero E, Debbané M, Schneider M, Badoud D, Eliez S (2016), Schizotypal traits in adolescents with 22q11.2 deletion syndrome: validity, reliability and risk for psychosis., in Psychological medicine, 46(5), 1005-13.
Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm.
Schneider Maude, Eliez Stephan, Birr Julie, Menghetti Sarah, Debbané Martin, Van der Linden Martial (2016), Multitasking Abilities in Adolescents With 22q11.2 Deletion Syndrome: Results From an Experimental Ecological Paradigm., in American journal on intellectual and developmental disabilities, 121(2), 151-64.
Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.
Mlynarski Elisabeth E, Xie Michael, Taylor Deanne, Sheridan Molly B, Guo Tingwei, Racedo Silvia E, McDonald-McGinn Donna M, Chow Eva W C, Vorstman Jacob, Swillen Ann, Devriendt Koen, Breckpot Jeroen, Digilio Maria Cristina, Marino Bruno, Philip Nicole, Simon Tony J, Roberts Amy E, Piotrowicz Małgorzata, Bearden Carrie E, Eliez Stephan, Gothelf Doron, Coleman Karlene, Kates Wendy R, Devoto Marcella, Zackai Elaine, Heine-Suñer Damian, Goldmuntz Elizabeth, Bassett Anne S, Morrow Bernice E, Emanuel Beverly S, Emanuel Beverly S (2016), Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome., in Human genetics, 135(3), 273-85.
Visual processing of emotional dynamic faces in 22q11.2 deletion syndrome.
Franchini M, Schaer M, Glaser B, Kott-Radecka M, Debanné M, Schneider M, Menghetti S, Sander D, Eliez S (2016), Visual processing of emotional dynamic faces in 22q11.2 deletion syndrome., in Journal of intellectual disability research : JIDR, 1.
Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome.
Padula Maria Carmela, Schaer Marie, Scariati Elisa, Schneider Maude, Van De Ville Dimitri, Debbané Martin, Eliez Stephan (2015), Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome., in Journal of neurodevelopmental disorders, 7(1), 23-23.
Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome.
Mlynarski Elisabeth E, Sheridan Molly B, Xie Michael, Guo Tingwei, Racedo Silvia E, McDonald-McGinn Donna M, Gai Xiaowu, Chow Eva W C, Vorstman Jacob, Swillen Ann, Devriendt Koen, Breckpot Jeroen, Digilio Maria Cristina, Marino Bruno, Dallapiccola Bruno, Philip Nicole, Simon Tony J, Roberts Amy E, Piotrowicz Małgorzata, Bearden Carrie E, Eliez Stephan, Gothelf Doron, Coleman Karlene, Kates Wendy R, Devoto Marcella, Zackai Elaine, Heine-Suñer Damian, Shaikh Tamim H, Bassett Anne S, Goldmuntz Elizabeth, Morrow Bernice E, Emanuel Beverly S, Emanuel Beverly S (2015), Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome., in American journal of human genetics, 96(5), 753-64.
Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome.
Vorstman Jacob A S, Breetvelt Elemi J, Duijff Sasja N, Eliez Stephan, Schneider Maude, Jalbrzikowski Maria, Armando Marco, Vicari Stefano, Shashi Vandana, Hooper Stephen R, Chow Eva W C, Fung Wai Lun Alan, Butcher Nancy J, Young Donald A, McDonald-McGinn Donna M, Vogels Annick, van Amelsvoort Therese, Gothelf Doron, Weinberger Ronnie, Weizman Abraham, Klaassen Petra W J, Koops Sanne, Kates Wendy R, Antshel Kevin M, Simon Tony J, Ousley Opal Y, Swillen Ann, Gur Raquel E, Bearden Carrie E, Kahn René S, Bassett Anne S, Bassett Anne S (2015), Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome., in JAMA psychiatry, 72(4), 377-85.
Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome
Demily C., Demily C., Rossi M., Rossi M., Schneider M., Edery P., Edery P., Leleu A., D'Amato T., D'Amato T., Franck N., Franck N., Eliez S., Eliez S. (2014), Neurocognitive and psychiatric management of the 22q11.2 deletion syndrome, in Encephale, 41(3), 266-273.
Identifying 22q11.2 deletion syndrome and psychosis using resting-state connectivity patterns.
Scariati Elisa, Schaer Marie, Richiardi Jonas, Schneider Maude, Debbané Martin, Van De Ville Dimitri, Eliez Stephan (2014), Identifying 22q11.2 deletion syndrome and psychosis using resting-state connectivity patterns., in Brain topography, 27(6), 808-21.
Congenital heart disease is associated with reduced cortical and hippocampal volume in patients with 22q11.2 deletion syndrome.
Fountain Daniel M, Schaer Marie, Mutlu A Kadir, Schneider Maude, Debbané Martin, Eliez Stephan (2014), Congenital heart disease is associated with reduced cortical and hippocampal volume in patients with 22q11.2 deletion syndrome., in Cortex; a journal devoted to the study of the nervous system and behavior, 57, 128-42.
Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?
Tomescu Miralena I, Rihs Tonia A, Becker Robert, Britz Juliane, Custo Anna, Grouiller Frédéric, Schneider Maude, Debbané Martin, Eliez Stephan, Michel Christoph M (2014), Deviant dynamics of EEG resting state pattern in 22q11.2 deletion syndrome adolescents: A vulnerability marker of schizophrenia?, in Schizophrenia research, 157(1-3), 175-81.
Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach.
Schneider Maude, Schaer Marie, Mutlu A Kadir, Menghetti Sarah, Glaser Bronwyn, Debbané Martin, Eliez Stephan (2014), Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach., in European child & adolescent psychiatry, 23(6), 425-36.
Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome.
Schneider Maude, Debbané Martin, Bassett Anne S, Chow Eva W C, Fung Wai Lun Alan, van den Bree Marianne, Owen Michael, Murphy Kieran C, Niarchou Maria, Kates Wendy R, Antshel Kevin M, Fremont Wanda, McDonald-McGinn Donna M, Gur Raquel E, Zackai Elaine H, Vorstman Jacob, Duijff Sasja N, Klaassen Petra W J, Swillen Ann, Gothelf Doron, Green Tamar, Weizman Abraham, Van Amelsvoort Therese, Evers Laurens, Boot Erik, Shashi Vandana, Hooper Stephen R, Bearden Carrie E, Jalbrzikowski Maria, Armando Marco, Vicari Stefano, Murphy Declan G, Ousley Opal, Campbell Linda E, Simon Tony J, Eliez Stephan, Eliez Stephan (2014), Psychiatric disorders from childhood to adulthood in 22q11.2 deletion syndrome: results from the International Consortium on Brain and Behavior in 22q11.2 Deletion Syndrome., in The American journal of psychiatry, 171(6), 627-39.
Individuals with 22q11.2 deletion syndrome are impaired at explicit, but not implicit, discrimination of local forms embedded in global structures.
Giersch Anne, Glaser Bronwyn, Pasca Catherine, Chabloz Mélanie, Debbané Martin, Eliez Stephan (2014), Individuals with 22q11.2 deletion syndrome are impaired at explicit, but not implicit, discrimination of local forms embedded in global structures., in American journal on intellectual and developmental disabilities, 119(3), 261-75.
Predominant negative symptoms in 22q11.2 deletion syndrome and their associations with cognitive functioning and functional outcome.
Schneider Maude, Van der Linden Martial, Menghetti Sarah, Glaser Bronwyn, Debbané Martin, Eliez Stephan (2014), Predominant negative symptoms in 22q11.2 deletion syndrome and their associations with cognitive functioning and functional outcome., in Journal of psychiatric research, 48(1), 86-93.
Sex differences in thickness, and folding developments throughout the cortex.
Mutlu A Kadir, Schneider Maude, Debbané Martin, Badoud Deborah, Eliez Stephan, Schaer Marie (2013), Sex differences in thickness, and folding developments throughout the cortex., in NeuroImage, 82, 200-7.
Altered auditory processing in frontal and left temporal cortex in 22q11.2 deletion syndrome: a group at high genetic risk for schizophrenia.
Rihs Tonia A, Tomescu Miralena I, Britz Juliane, Rochas Vincent, Custo Anna, Schneider Maude, Debbané Martin, Eliez Stephan, Michel Christoph M (2013), Altered auditory processing in frontal and left temporal cortex in 22q11.2 deletion syndrome: a group at high genetic risk for schizophrenia., in Psychiatry research, 212(2), 141-9.
Risk factors and evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal two-centers study
Gothelf Doron, Schneider Maude, Green Tamar, Debbané Martin, Frisch A, Glaser Bronwyn, Zilkha H, Schaer Marie, Weizman A, Eliez Stephan (2013), Risk factors and evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal two-centers study, in Journal of the American Academy of Child and Adolescent Psychiatry, 1192.
Coping strategies mediate the effect of stressful life events on schizotypal traits and psychotic symptoms in 22q11.2 Deletion Syndrome
Armando Marco, Sandini Corrado, Chambaz Maëlle, Schaer Marie, Schneider Maude, Eliez Stephan, Coping strategies mediate the effect of stressful life events on schizotypal traits and psychotic symptoms in 22q11.2 Deletion Syndrome, in Schizophrenia Bulletin, 1.
Cortical dysconnectivity measured by structural covariance is associated with the presence of psychotic symptoms in 22q11.2 deletion syndrome
Sandini Corrado, Scariati Elisa, Padula Maria Carmela, Schneider Maude, Schaer Marie, Van de Ville Dimitri, Eliez Stephan, Cortical dysconnectivity measured by structural covariance is associated with the presence of psychotic symptoms in 22q11.2 deletion syndrome, in Biological psychiatry: cognitive neuroscience and neuroimaging, 1.
Online social skills training for adolescents and young adults with 22q11.2 deletion syndrome using the SOSTA-22 digital version
Glaser Bronwyn, Eliez Stephan, Freitag Christine, Cholemkery Hannah, Schneider Maude, Online social skills training for adolescents and young adults with 22q11.2 deletion syndrome using the SOSTA-22 digital version, in Journal of Behavioral and Brain Science, 1.

Collaboration

Group / person Country
Types of collaboration
UNIGE Developmental Imaging and Psychopathology lab - Prof. Marie Schaer Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
- Exchange of personnel
Max Planck Institute for Human Cognitive and Brain Sciences - Dr. Pascal Vrticka Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
EPFL Medical Image Processing lab - Prof. Dimitri Van de Ville Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Exchange of personnel
UNIGE neurology and imaging of cognition - Prof. Patrick Vuilleumier Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Universitäre Psychiatrische Dienste Bern (UPD) - Dr. Frauke Schultze-Lutter Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
EPFL Laboratory of Cognitive Neuroscience - Prof. Olaf Blanke Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Stanford University Psychiatry and Behavioral Sciences lab - Prof. Vinod Menon United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Dr François Lazeyras/ CIBM Geneva University School of Medecine Switzerland (Europe)
- Research Infrastructure
FMI Basel - Prof. Pico Caroni Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
UNIGE Unité de Neuropsychologie et Psychopathologie Cognitive - Prof. Martial Van der Linden Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Tel Aviv University - Prof. Doron Gothelf Israel (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Albert Einstein College of Medicine - Prof. Bernice Morrow United States of America (North America)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
International Brain and Behavior Consortium on 22q11.2 deletion Syndrome United States of America (North America)
- Publication
Istituto Italiano di Tecnologia - Dr. Francesco Papaleo Italy (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
UNIGE Developmental Imaging and Psychopathology lab - Dr. Bronwyn Glaser Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
CHUV Service de radiodiagnostic et radiologie interventionnelle - Prof. Patric Hagmann Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
UNIGE Functional Brain Mapping lab - Prof. Christoph Michel Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
NCCR-Synapsy 2nd conference on The Neurobiology of mental Health Poster Modulation of stress reactivity by the social context: relevance for psychosis? 24.01.2018 Geneva, Switzerland Dubourg Lydia; Schneider Maude;
French Congress of Psychiatry 2017 Talk given at a conference L'étude de la microdélétion 22q11.2 peut-elle nous éclairer sur la prévention des troubles psychotiques chez l'enfant et l'adolescent? 29.11.2017 Lyon, France Eliez Stephan;
European Society of Child and Adolescent Psychiatry 2017 Talk given at a conference Visual processing of complex social scenes in 22q11DS: relevance for social impairments 09.07.2017 Geneva, Switzerland Dubourg Lydia;
European Society of Child and Adolescent Psychiatry 2017 Talk given at a conference 22q11DS: overview of cognitive and clinical characteristics 09.07.2017 Geneva, Switzerland Eliez Stephan; Schneider Maude;
European Society of Child and Adolescent Psychiatry 2017 Talk given at a conference Altered structural network architecture is predic symptoms in patients with 22q11.2 deletion syndrome 09.07.2017 Geneva, Switzerland Padula Maria Carmela;
European Society of Child and Adolescent Psychiatry 2017 Talk given at a conference Social impairments across the psychosis continuum 09.07.2017 Geneva, Switzerland Schneider Maude; Debbané Martin;
NCCR Synapsy Annual Retreat 2017 Talk given at a conference Overview of achievements of the 22q11DS cohort 31.03.2017 Villars, Switzerland Eliez Stephan;
NCCR Synapsy Annual Retreat 2017 Poster ultra high-risk status and transition to psychosis in 22q11DS 31.03.2017 Villars, Switzerland Schneider Maude;
NCCR Synapsy Annual Retreat 2017 Poster Reward processing in 22q11DS 31.03.2017 Geneva, Switzerland Dubourg Lydia;
NCCR Synapsy Annual Retreat 2017 Poster Altered functional connectivity in 22q11DS 31.03.2017 Villars, Switzerland Padula Maria Carmela;
Women in Machine Learning conference Poster Predicting psychotic symptoms from DTI-based structural connectivity in patients with 22q11DS 04.12.2016 Barcelona, Spain Padula Maria Carmela;
Early Intervention in Mental Health conference (IEPA) 2016 Poster Ultra high-risk status and transition to psychosis in 22q11.2 Deletion Syndrome 20.10.2016 Milan, Italy Schneider Maude;
Early Intervention in Mental Health conference (IEPA) 2016 Talk given at a conference Symposium: Schizotypy in youths: stress, cognition and relationships with transition to psychosis 20.10.2016 Milan, Italy Schneider Maude; Debbané Martin;
Organization for Human Brain Mapping (OHBM) conference 2016 Poster Multimodal large-scale networks connectivity in 22q11.2 deletion syndrome 26.06.2016 Geneva, Switzerland Padula Maria Carmela;
Organization for Human Brain Mapping (OHBM) conference 2016 Poster Reward processes, white matter pathways of the reward system and negative symptoms in 22q11DS 26.06.2016 Geneva, Switzerland Dubourg Lydia;
BBL-CIBM research day 2016 Talk given at a conference Multimodal network-based analysis of brain connectivity in 22q11.2 deletion syndrome. 02.05.2016 Geneva, Switzerland Padula Maria Carmela;
NCCR Synapsy - 1st Neurobiology of Mental Health Conference Poster Reward processes, structural connectivity of the reward system and negative symptoms in the 22q11DS 07.04.2016 Geneva, Switzerland Dubourg Lydia;
NCCR Synapsy - 1st Neurobiology of Mental Health Conference Poster Large-scale network connectivity in 22q11DS 07.04.2016 Geneva, Switzerland Padula Maria Carmela;
NCCR Synapsy Annual Retreat 2016 Talk given at a conference Update on the 22q11DS cohort 16.03.2016 Villars, Switzerland Eliez Stephan;
NCCR Synapsy Annual Retreat 2016 Poster Large-scale network connectivity in 22q11DS 16.03.2016 Villars, Switzerland Padula Maria Carmela;
NCCR Synapsy Annual Retreat 2016 Poster Reward processes, structural connectivity of the reward system and negative symptoms in the 22q11DS 16.03.2016 Villars, Switzerland Dubourg Lydia;
OHBM Alpine Chapter 2015 Poster Triple network connectivity in 22q11.2 deletion syndrome 03.11.2015 Vienna, Austria Padula Maria Carmela;
BBL-CIBM research day Talk given at a conference Multimodal network-based analysis of brain connectivity in 22q11.2 deletion syndrome. 20.09.2015 Geneva, Switzerland Padula Maria Carmela;
ECNP conference 2015 Talk given at a conference Cognitive risk factors for schizophrenia spectrum disorders in children with 22q11.2DS 29.08.2015 Amsterdam, Netherlands Schneider Maude;
European Society of Child and Adolescent Psychiatry 2015 Talk given at a conference Symposium: 22q11.2 deletion syndrome as a framework to better understand the development of psychosis 20.06.2015 Madrid, Spain Schneider Maude; Eliez Stephan;
Organization for Human Brain Mapping (OHBM) conference 2015 Poster Mapping white matter fibers to the cortical surface: local and global connectivity throughout the cortex 14.06.2015 Honolulu, United States of America Padula Maria Carmela;
NCCR Synapsy Annual Retreat 2015 Poster Face processing in 22q11DS: an eye-tracking study 17.04.2015 Villars, Switzerland Zaharia Alexandra;
NCCR Synapsy Annual Retreat 2015 Talk given at a conference Update on the 22q11DS cohort study 17.04.2015 Villars, Switzerland Schneider Maude; Eliez Stephan;
NCCR Synapsy Annual Retreat 2015 Poster Displaying surfaced-based mesures of local and distant connectivity over the cortex. 17.04.2015 Villars, Switzerland Padula Maria Carmela;
2nd international FHU-TRANSLAD seminar Talk given at a conference Une approche neuropsychologique des symptômes négatifs dans la del22q11.2 07.10.2014 Dijon, France Schneider Maude;
9th Biennal International 22q11.2 deletion syndrome meeting Talk given at a conference Atypical developmental trajectories of cognitive functioning in 22q11DS 18.06.2014 Palma de Mallorca, Spain Eliez Stephan;
9th Biennal International 22q11.2 deletion syndrome meeting Talk given at a conference Does impaired multitasking underlie the development of negative symptoms in adolescents with 22q11.2 deletion syndrome? A study based on a naturalistic experimental paradigm 18.06.2014 Palma de Mallorca, Spain Schneider Maude;
NCCR Synapsy Annual Retreat 2014 Talk given at a conference Update on the 22q11DS cohort 04.04.2014 Villars, Switzerland Eliez Stephan;
NCCR Synapsy Annual Retreat 2014 Poster Reduced default mode network connectivity correlates with metacognitive impairments in 22q11.2 deletion syndrome 04.04.2014 Villars, Switzerland Padula Maria Carmela;
Basic and Clinical Multimodal Imaging conference Talk given at a conference 22q11.2 deletion syndrome: a neurodevelopmental model to understand psychosis 05.09.2013 Geneva, Switzerland Eliez Stephan;
16th European Conference on Developmental Psychology Talk given at a conference Attenuated negative symptoms, dysfunctional beliefs and the experience of pleasure in adolescents with 22q11.2 deletion syndrome 04.09.2013 Lausanne, Switzerland Schneider Maude;
European Society of Child and Adolescent Psychiatry 2013 Talk given at a conference Symposium: Cognitive, behavioural & neuroimaging trajectories in 22q11.2 Deletion Syndrome: A window into the risk factors for the development of psychiatric disorders 06.07.2013 Dublin, Ireland Schneider Maude; Eliez Stephan;
Swiss Federation of Clinical Neuro-Societies Congress Talk given at a conference 22q11 deletion syndrome: a neurodevelopmental model for psychosis from gene to brain to behavior 05.06.2013 Montreux, Switzerland Eliez Stephan;


Knowledge transfer events

Active participation

Title Type of contribution Date Place Persons involved
2nd 22q11 Europe meeting Talk 07.10.2017 Dublin, Ireland Eliez Stephan; Dubourg Lydia; Schneider Maude; Padula Maria Carmela;
Relais 22 general assembly 2017 Workshop 22.04.2017 Bruxelles, Belgium Schneider Maude;
Generation 22 Symbiosium 2016 Talk 14.10.2016 Paris, France Padula Maria Carmela; Eliez Stephan; Schneider Maude;
1st 22q11 Europe meeting Talk 10.10.2015 Bruxelles, Belgium Eliez Stephan; Padula Maria Carmela; Dubourg Lydia; Schneider Maude; Zaharia Alexandra;
Generation 22 Symbiosium 2014 Talk 10.10.2014 Paris, France Schneider Maude; Eliez Stephan; Padula Maria Carmela;
Relais 22 general assembly 2014 Talk 17.05.2014 Bruxelles, Belgium Schneider Maude; Eliez Stephan;
20th Annual International Scientific Meeting of the Velo-Cardio-Facial Syndrome Educational Foundation Talk 18.07.2013 Dublin, Ireland Schneider Maude; Eliez Stephan;


Self-organised

Title Date Place
Connect 22 annual meeting 2017 04.11.2017 Geneva, Switzerland
Connect 22 annual meeting 2016 12.11.2016 Geneva, Switzerland
Connect 22 annual meeting 2015 07.11.2015 Geneva, Switzerland
Connect 22 annual meeting 2014 04.10.2014 Geneva, Switzerland
Connect 22 annual meeting 2013 05.10.2013 Geneva, Switzerland

Associated projects

Number Title Start Funding scheme
63135 Neurobehavioral Phenotype and Brain Development in velo-cardio- facial syndrome (de122q11.2). (zu SCORE B) 01.10.2001 Project funding
121996 Geneva VCFS longitudinal project: neurobehavioral outcomes in adolescents and adults 01.10.2009 Project funding (special)
121996 Geneva VCFS longitudinal project: neurobehavioral outcomes in adolescents and adults 01.10.2009 Project funding (special)
102864 Neurobehavioral Phenotype and Brain Development in velo-cardio-facial syndrome (del22q11.2) - a longitudinal study 01.10.2004 SNSF Professorships
179404 The Swiss 22q11DS longitudinal cohort: understanding psychosis proneness through negative symptoms 01.10.2018 Project funding
174206 Towards an embodied and ecological understanding of social impairments in neurodevelopmental disorders 01.04.2018 Ambizione

Abstract

Velo-cardio-facial syndrome (VCFS), or 22q11.2 deletion syndrome, is the most common microdeletion disorder in humans, affecting approximately 1 in 3000 live births. Sixty genes are encoded in the commonly-deleted region, a few of which are highly expressed in brain tissue and likely to be essential for normal brain development. Over the past two decades, numerous studies have helped researchers differentiate the cerebral phenotype in VCFS. Reduced cerebral volume has been a consistent hallmark of the syndrome across ages, but specifics about the timing of the alterations of the different cerebral regions also have been observed. These impairments likely underlie the many cognitive, social, and behavioral abnormalities associated with the syndrome. Specifically, prodromal psychotic symptoms appear early on in the syndrome, with a high incidence of positive symptoms reported by affected children and adolescents. Thirty percent of affected patients go on to develop psychosis, making VCFS a genetic model for schizophrenia. Given that VCFS and its associated symptoms result from a known genetic origin, the biological and behavioral characteristics of the syndrome provide an optimal framework for conceptualizing the associations between genes, brain structure and function, and behavior throughout development. However, although the deletion is now frequently detected within the first years of life, the feasibility to follow a large cohort longitudinally is rare. We are fortunate to have developed one of only two or three thoroughly documented longitudinal cohorts in the world, which we have closely followed since 2001. Patients in the Swiss VCFS Cohort are evaluated using standardized cognitive measures, experimental cognitive tasks using eyetracking, behavioral questionnaires, semi-structured psychiatric interviews and questionnaires, and structural and functional neuroimaging. This proposal requests funding for a fourth timepoint, which would provide sufficient statistical power for modeling interactions between genetics, measures of brain structure and function, and resulting behavioral, cognitive, and psychotic symptomatology. The proposed project would enable us to reach a big enough sample size (120 patients/120 controls at Time 1, 80 patients/80 controls at Time 2, 50 patients/50 controls at Time 3, up to 35 patients/35 controls at Time 4) to apply non-linear modeling on the data and have enough statistical power to compare subgroups of patients. The aims of this proposal and for the continuation of our longitudinal work are twofold: 1) To measure neurodevelopmental patterns in VCFS to identify the relationships between specific genetic polymorphisms pertinent to the 22q11.2 region and structural brain changes, brain organization and function, cognition and behavior. 2) To understand how biological markers, such as changes in complex brain organization and cognitive skill sets, discriminate between adolescents and young adults who are at higher risk for psychosis. Longitudinal data enable us to identify prodromal traits that precede adolescence in individuals with psychosis, making it possible to isolate the factors that put a patient at “higher risk” for psychiatric problems later on. For example, we will be able to further understand inter-individual variability in the clinical expression of psychotic symptoms, how to predict psychotic symptoms in affected and unaffected individuals, how cortical volume changes with time in patients with and without psychosis, and how structural connectivity in the brain affects functional connectivity and the recruitment of functional areas for completing a task.The current research has important implications for Child Psychiatry. In addition to having a direct impact on our knowledge of VCFS, the integration of neuroscience and clinical applications in the study will inform our understanding of other neurodevelopmental disorders in the general population, such as autism or psychosis. Unlike studies focusing solely on a special population, this study contributes to science by creating neuroimaging techniques that are now available in open-source quantitative software packages like Freesurfer. It also has encouraged inter-institutional collaboration in Switzerland between the Radiology, Neuroscience, Signal Processing and Psychiatry departments, and data sharing with international consortiums studying VCFS. Lastly, the results will assist in predicting the neurodevelopmental trajectories of individuals with VCFS, enabling clinicians to take into account the context of the disorder and establish a risk prevention strategy for psychosis starting from early childhood based on scientific data.
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