Association of Disrupted in Schizophrenia 1 (DISC1) missense variants with ultra-resistant schizophrenia.
Three common missense variants of the Disrupted in Schizophrenia 1 (DISC1) gene, rs3738401 (Q264R), rs6675281 (L607F) and rs821616 (S704C), have been variably associated with the risk of schizophrenia. In a case-control study, we examine whether these gene variants are associated with schizophrenia and ultra-resistant schizophrenia (URS) in a population of French Caucasian patients. The URS phenotype is characterized according to stringent criteria as patients who experience no clinical, social and/or occupational remission in spite of treatment with clozapine and at least two periods of treatment with distinct conventional or atypical antipsychotic drugs. We find a significant association between DISC1 missense variants and URS. The association with rs3738401 remains significant after appropriate correction for multiple testing. These results suggest that the DISC1 rs3738401 missense variant is statistically linked with ultra-resistance to antipsychotic treatment.
INSERM U894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Paris, France.
F
F
Mouaffak
O
O
Kebir
M
M
Chayet
S
S
Tordjman
M N
MN
Vacheron
B
B
Millet
N
N
Jaafari
A
A
Bellon
J P
JP
Olié
M-O
MO
Krebs
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D012565:Schizophrenic Psychology; D017211:Treatment Failure; D044465:White People / Q000235:genetics; D055815:Young Adult
D014150:Antipsychotic Agents; C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins