Risk factors for the emergence of psychotic disorders in adolescents with 22q11.2 deletion syndrome.
OBJECTIVE
The 22q11.2 deletion syndrome is the most common known genetic risk factor for the development of schizophrenia. The authors conducted a longitudinal evaluation of adolescents with 22q11.2 deletion syndrome to identify early risk factors for the development of psychotic disorders.


METHODS
Sixty children, 31 with 22q11.2 deletion syndrome and 29 comparison subjects with idiopathic developmental disability matched for age and IQ, underwent a baseline evaluation between 1998 and 2000; of these, 51 children (28 and 23 in the two groups, respectively) underwent follow-up evaluation between 2003 and 2005. A standardized comprehensive psychiatric, psychological, and adaptive functioning evaluation was conducted in both waves. Participants with 22q11.2 deletion syndrome were also genotyped for the catechol O-methyltransferase (COMT) Met/Val polymorphism and underwent magnetic resonance imaging scans.


RESULTS
The two groups had similar baseline neuropsychiatric profiles. At follow-up, 32.1% of subjects with 22q11.2 deletion syndrome had developed psychotic disorders as compared with 4.3% of comparison subjects. In the 22q11.2 deletion syndrome group, baseline subthreshold psychotic symptoms interacted both with the COMT genotype and with baseline symptoms of anxiety or depression to predict 61% of the variance in severity of psychosis at follow-up evaluation. Lower baseline verbal IQ was also associated with more severe psychotic symptoms at follow-up evaluation.


CONCLUSIONS
Genetic, cognitive, and psychiatric risk factors for the evolution of psychotic disorders in 22q11.2 deletion syndrome during adolescence were identified. Early intervention in the subgroup of children with subthreshold signs of psychosis and internalizing symptoms (especially anxiety symptoms) may reduce the risk of developing psychotic disorders during adolescence.
Gothelf
Doron
D
Department of Child Psychiatry, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel 49202. gothelf@post.tau.ac.il
Feinstein
Carl
C
Thompson
Tracy
T
Gu
Eugene
E
Penniman
Lauren
L
Van Stone
Ellen
E
Kwon
Hower
H
Eliez
Stephan
S
Reiss
Allan L
AL
D000293:Adolescent; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D003072:Cognition Disorders / Q000235:genetics; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics; D004062:DiGeorge Syndrome / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D009483:Neuropsychological Tests; D010555:Personality Inventory; D011110:Polymorphism, Genetic; D011618:Psychotic Disorders / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D012720:Severity of Illness Index
D002394:Catechol O-Methyltransferase