The Psychosis Spectrum in 22q11.2 Deletion Syndrome Is Comparable to That of Nondeleted Youths.
Chromosome 22q11.2 deletion syndrome (22q11DS) is a promising model for studying psychosis risk. Direct comparisons of psychosis features between 22q11DS and nondeleted (ND) individuals are limited by inconsistency and small samples. In the largest study to date, we compare 22q11DS to ND in comorbidities, functioning, cognition, and psychosis features across the full range of overall severity.



ND youths (n = 150) ages 9 to 24 years were matched to 22q11DS individuals (n = 150) on age and sex, stratifying for presence of psychosis spectrum disorder. Individuals were evaluated for psychosis using the Structured Interview for Prodromal Syndromes, and for attention-deficit/hyperactivity, substance-related, and mood disorders. Differential item functioning analysis addressed whether 22q11DS differs from ND in the probability of clinically significant ratings while holding constant the overall level of psychosis.



Onset of psychosis proneness was similar among 22q11DS (mean: 11.0 years) and ND (mean: 12.1 years) individuals. Accounting for higher overall psychosis symptoms, 22q11DS participants were still more likely to manifest impaired stress tolerance, avolition, and ideational richness; ND individuals were more likely to exhibit unusual thoughts, persecutory ideas, and bizarre thinking. Cognition was impaired in 22q11DS, but it did not correlate with symptoms except ideational richness. Comorbid anxiety disorders were more likely in psychosis spectrum 22q11DS; substance-related disorders were more likely in ND. Global assessment of function was similar in 22q11DS and ND individuals, except among those with low total Structured Interview for Prodromal Syndromes scores.



Individuals with 22q11DS share overarching similarities with ND individuals in psychosis symptoms and age of onset for psychosis proneness; this continues to support the 22q11DS model as a valuable window into mechanisms contributing to psychosis.
Department of Psychiatry, Philadelphia, Pennsylvania. Electronic address: suntang@upenn.edu.
Sunny X
SX
Tang
Department of Psychiatry, Philadelphia, Pennsylvania.
Tyler M
TM
Moore
Department of Psychiatry, Philadelphia, Pennsylvania.
Monica E
ME
Calkins
Department of Psychiatry, Philadelphia, Pennsylvania; Department of Child and Adolescent Psychiatry, Philadelphia, Pennsylvania.
James J
JJ
Yi
Department of Psychiatry, Philadelphia, Pennsylvania.
Adam
A
Savitt
Department of Psychiatry, Philadelphia, Pennsylvania.
Christian G
CG
Kohler
Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Margaret C
MC
Souders
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Elaine H
EH
Zackai
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Donna M
DM
McDonald-McGinn
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
Beverly S
BS
Emanuel
Department of Psychiatry, Philadelphia, Pennsylvania.
Ruben C
RC
Gur
Department of Psychiatry, Philadelphia, Pennsylvania; Department of Child and Adolescent Psychiatry, Philadelphia, Pennsylvania.
Raquel E
RE
Gur
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D003071:Cognition; D015897:Comorbidity; D004062:DiGeorge Syndrome / Q000453:epidemiology* / Q000523:psychology*; D005260:Female; D006801:Humans; D008297:Male; D019964:Mood Disorders / Q000453:epidemiology*; D010414:Pennsylvania / Q000453:epidemiology; D011618:Psychotic Disorders / Q000453:epidemiology* / Q000523:psychology*; D019966:Substance-Related Disorders / Q000453:epidemiology*; D013997:Time Factors; D055815:Young Adult
22q11.2 Deletion syndrome; Clinical high risk; DiGeorge syndrome; Prodromal; Psychosis; Schizophrenia