DTNBP1 genotype influences cognitive decline in schizophrenia.
OBJECTIVE
Intellectual decline is common in schizophrenia and predicts functional outcome. While many patients undergo intellectual decline that typically predates the onset of symptoms, few studies have investigated the underlying mechanism through which this occurs. The current study assessed the relationship between intellectual decline in schizophrenia and genetic variation in dysbindin-1 (DTNBP1).


METHODS
We assessed cognitive decline in 183 Caucasian patients with schizophrenia using a proxy measure of premorbid IQ with which current general cognitive ability (g) was compared. We then tested for a relationship between the risk haplotype identified in previous work (CTCTAC) and intellectual decline.


RESULTS
We found that carriers of the CTCTAC haplotype, demonstrated a significantly greater decline in IQ as compared with non-carriers (p=0.05).


CONCLUSIONS
These data suggest that DTNBP1 influences the severity of intellectual decline in schizophrenia and may represent one underlying cause for heterogeneity in cognitive course.
Burdick
Katherine E
KE
Division of Psychiatry Research, The Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, NY 11004, United States. kburdick@lij.edu
Goldberg
Terry E
TE
Funke
Birgit
B
Bates
John A
JA
Lencz
Todd
T
Kucherlapati
Raju
R
Malhotra
Anil K
AK
D000328:Adult; D002352:Carrier Proteins / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D018450:Disease Progression; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007360:Intelligence / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D014888:Wechsler Scales
D002352:Carrier Proteins; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins