title: Negative subthreshold psychotic symptoms distinguish 22q11.2 deletion syndrome from other neurodevelopmental disorders: A two-site study.
abstract: About one third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop schizophrenia. Notably, a full-blown psychotic disorder is usually preceded by subthreshold symptoms. Therefore, it is important to identify early signs of psychosis in this population, a task that is complicated by the intellectual disabilities typically seen in 22q11.2DS. We aimed to identify subthreshold psychotic symptoms that distinguish 22q11.2DS from other neurodevelopmental disorders. The study included two independent cohorts from Tel Aviv and Philadelphia. 22q11.2DS (N=171) and typically developing (TD; N=832) individuals were enrolled at both sites and further compared to two groups with intellectual disabilities: Williams syndrome (WS; N=21) in the Tel Aviv cohort and idiopathic developmental disabilities (IDD; N=129) in the Philadelphia cohort. Participants and their primary caregivers were interviewed with the Structured Interview for Prodromal Symptoms (SIPS) and psychopathologies were assessed using standardized tools; general cognitive abilities were assessed with the Computerized Neurocognitive Battery. Negative/disorganized subthreshold syndrome was significantly more common in the 22q11.2DS group than in the WS (OR=3.90, 95% CI=1.34-11.34) or IDD (OR=5.05, 95% CI=3.01-10.08) groups. The 22q11.2DS group had higher scores than the two intellectual disabilities groups on several SIPS negative items, including avolition and decreased expression of emotion. Overall, there were few significant correlations between level of cognitive deficits and severity of negative symptoms in 22q11.2DS and only in the Tel Aviv cohort. Our findings suggest that 22q11.2DS individuals at the age of risk for developing psychosis should be closely monitored for negative symptoms.
authors.affiliation: The Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ehud
authors.initials: E
authors.lastname: Mekori-Domachevsky
authors.affiliation: The Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Guri
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA; Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Yi
authors.affiliation: The Behavioral Neurogenetics Center, The Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Weisman
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA.
authors.forename: Sunny X
authors.initials: SX
authors.lastname: Tang
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Division of Psychiatry, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Raz
authors.initials: R
authors.lastname: Gross
authors.affiliation: Division of Human Genetics, and 22q and You Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.affiliation: Division of Human Genetics, and 22q and You Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
authors.affiliation: Division of Human Genetics, and 22q and You Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Geha Mental Health Center, Petah Tikva, Israel.
authors.forename: Gil
authors.initials: G
authors.lastname: Zalsman
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Geha Mental Health Center, Petah Tikva, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel.
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA.
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, PA, USA; Department of Child and Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
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, Tel Hashomer, 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
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D015331:Cohort Studies; D015897:Comorbidity; D003430:Cross-Sectional Studies; D002658:Developmental Disabilities / Q000175:diagnosis / Q000523:psychology; D004062:DiGeorge Syndrome / Q000175:diagnosis* / Q000523:psychology*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007406:Interview, Psychological; D008297:Male; D011618:Psychotic Disorders / Q000523:psychology*; D018980:Williams Syndrome / Q000175:diagnosis / Q000523:psychology; D055815:Young Adult
keywords: Computerized Neurocognitive Battery (CNB); Negative symptoms; Structured Interview for Prodromal Symptoms (SIPS); Velocardiofacial syndrome; Williams syndrome