title: Performance on a computerized neurocognitive battery in 22q11.2 deletion syndrome: A comparison between US and Israeli cohorts.
abstract: Increasingly, the effects of copy number variation (CNV) in the genome on brain function and behaviors are recognized as means to elucidate pathophysiology of psychiatric disorders. Such studies require large samples and we characterized the neurocognitive profile of two cohorts of individuals with 22q11.2 deletion syndrome (22q11DS), the most common CNV associated with schizophrenia, in an effort to harmonize phenotyping in multi-site global collaborations. The Penn Computerized Neurocognitive Battery (PCNB) was administered to individuals with 22q11DS in Philadelphia (PHL; n=155, aged 12-40) and Tel Aviv (TLV; n=59, aged 12-36). We examined effect sizes of performance differences between the cohorts and confirmed the factor structure of PCNB performance efficiency in the combined sample based on data from a large comparison community sample. The cohorts performed comparably with notable deficits in executive function, episodic memory and social cognition domains that were previously associated with abnormal neuroimaging findings in 22q11DS. In mixed model analysis, while there was a main effect for site for accuracy (number of correct response) and speed (time to correct response) independently, there were no main site effects for standardized efficiency (average of accuracy and speed). The fit of a structural model was excellent indicating that PCNB tests were related to the targeted cognitive domains. Thus, our results provide preliminary support for the use of the PCNB as an efficient tool for neurocognitive assessment in international 22q11DS collaborations.
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA, USA. Electronic address: yij@email.chop.edu.
authors.forename: James J
authors.initials: JJ
authors.lastname: Yi
authors.affiliation: The Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: ronnie.wein@gmail.com.
authors.forename: Ronnie
authors.initials: R
authors.lastname: Weinberger
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: tymoore@mail.med.upenn.edu.
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mcalkins@mail.med.upenn.edu.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: The Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: yaelig65@gmail.com.
authors.forename: Yael
authors.initials: Y
authors.lastname: Guri
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: mcginn@email.chop.edu.
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: zackai@email.chop.edu.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, USA; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: emanuel@email.chop.edu.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: raquel@mail.med.upenn.edu.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: The Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Ramat Gan, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: gothelf@post.tau.ac.il.
authors.forename: Doron
authors.initials: D
authors.lastname: Gothelf
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: gur@mail.med.upenn.edu.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D003431:Cross-Cultural Comparison; D004062:DiGeorge Syndrome / Q000503:physiopathology*; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D007557:Israel; D008297:Male; D061212:Memory, Episodic; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000592:standards; D012559:Schizophrenia / Q000235:genetics; D012938:Social Perception; D014481:United States; D055815:Young Adult
keywords: 22q11.2 deletion syndrome; Multisite; Neurocognition; Penn Computerized Neurocognitive Battery; Structural model