title: Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study.
abstract: Nearly one-third of individuals with 22q11.2 deletion syndrome (22q11.2DS) develop a psychotic disorder during life, most of them by early adulthood. Importantly, a full-blown psychotic episode is usually preceded by subthreshold symptoms. In the current study, 760 participants (aged 6-55 years) with a confirmed hemizygous 22q11.2 microdeletion have been recruited through 10 medical sites worldwide, as part of an international research consortium. Of them, 692 were nonpsychotic and with complete measurement data. Subthreshold psychotic symptoms were assessed using the Structured Interview for Prodromal Syndromes (SIPS). Nearly one-third of participants met criteria for positive subthreshold psychotic symptoms (32.8%), less than 1% qualified for acute positive subthreshold symptoms, and almost a quarter met criteria for negative/disorganized subthreshold symptoms (21.7%). Adolescents and young adults (13-25 years) showed the highest rates of subthreshold psychotic symptoms. Additionally, higher rates of anxiety disorders and attention deficit/hyperactivity disorder (ADHD) were found among the study participants with subthreshold psychotic symptoms compared to those without. Full-scale IQ, verbal IQ, and global functioning (GAF) scores were negatively associated with participants' subthreshold psychotic symptoms. This study represents the most comprehensive analysis reported to date on subthreshold psychosis in 22q11.2DS. Novel findings include age-related changes in subthreshold psychotic symptoms and evidence that cognitive deficits are associated with subthreshold psychosis in this population. Future studies should longitudinally follow these symptoms to detect whether and how early identification and treatment of these manifestations can improve long-term outcomes in those that eventually develop a psychotic disorder.
authors.affiliation: The Behavioral Neurogenetics Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.|Sackler Faculty of Medicine and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Omri
authors.initials: O
authors.lastname: Weisman
authors.affiliation: The Behavioral Neurogenetics Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Guri
authors.affiliation: Neuropsychiatry, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.|Department of Child & Adolescent Psychiatry, Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Donna M
authors.initials: DM
authors.lastname: McDonald-McGinn
authors.affiliation: Neuropsychiatry, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Neuropsychiatry, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Sunny X
authors.initials: SX
authors.lastname: Tang
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Beverly
authors.initials: B
authors.lastname: Emanuel
authors.affiliation: Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA.|Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Elaine H
authors.initials: EH
authors.lastname: Zackai
authors.affiliation: Developmental Imaging and Psychopathology Lab, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Eliez
authors.affiliation: Developmental Imaging and Psychopathology Lab, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Maude
authors.initials: M
authors.lastname: Schneider
authors.affiliation: Developmental Imaging and Psychopathology Lab, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
authors.forename: Marie
authors.initials: M
authors.lastname: Schaer
authors.affiliation: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY.
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Kates
authors.affiliation: Department of Psychology, Syracuse University, Syracuse, NY.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Antshel
authors.affiliation: Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY.
authors.forename: Wanda
authors.initials: W
authors.lastname: Fremont
authors.affiliation: Department of Pediatrics, Duke University Medical Center, Durham, NC.
authors.forename: Vandana
authors.initials: V
authors.lastname: Shashi
authors.affiliation: Department of Allied Health, University of North Carolina at Chapel Hill, Chapel Hill NC.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Hooper
authors.affiliation: Developmental Imaging and Psychopathology Lab, Faculty of Medicine, University of Geneva, Geneva, Switzerland.|Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience, Children Hospital Bambino Gesu, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Armando
authors.affiliation: Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience, Children Hospital Bambino Gesu, Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Vicari
authors.affiliation: Child and Adolescence Neuropsychiatry Unit, Department of Neuroscience, Children Hospital Bambino Gesu, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Pontillo
authors.affiliation: Department of Psychiatry and Behavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA.
authors.forename: Leila
authors.initials: L
authors.lastname: Kushan
authors.affiliation: Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Maria
authors.initials: M
authors.lastname: Jalbrzikowski
authors.affiliation: Department of Psychiatry and Behavioral Sciences and Psychology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA.
authors.forename: Carrie E
authors.initials: CE
authors.lastname: Bearden
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA.|Emory Autism Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Atlanta, GA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Cubells
authors.affiliation: Department of Human Genetics, Emory University School of Medicine, Atlanta, GA.|Emory Autism Center, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine Atlanta, GA.
authors.forename: Opal Y
authors.initials: OY
authors.lastname: Ousley
authors.affiliation: Department of Psychology, Emory University, Atlanta, GA.
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Walker
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA.
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Simon
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA.
authors.forename: Joel
authors.initials: J
authors.lastname: Stoddard
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA.
authors.forename: Tara A
authors.initials: TA
authors.lastname: Niendam
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
authors.forename: Marianne B M
authors.initials: MBM
authors.lastname: van den Bree
authors.affiliation: The Behavioral Neurogenetics Center, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer, Israel.|Sackler Faculty of Medicine and the Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Gothelf
mesh_terms: D000293:Adolescent; D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis / Q000453:epidemiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000453:epidemiology*; D002648:Child; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000453:epidemiology*; D015897:Comorbidity; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D008875:Middle Aged; D062706:Prodromal Symptoms; D011618:Psychotic Disorders / Q000175:diagnosis / Q000453:epidemiology*; D055815:Young Adult
keywords: DiGeorge syndrome; IQ; anxiety disorder; attention deficit/hyperactivity disorder (ADHD); global assessment of functioning (GAF); structured interview for prodromal syndromes; subthreshold psychotic symptoms; velocardiofacial syndrome