Systematic analysis of dopamine receptor genes (DRD1-DRD5) in antipsychotic-induced weight gain.
Antipsychotic-induced weight gain has emerged as a serious complication in the treatment of patients with most antipsychotics. We have conducted the first in-depth examination of dopamine receptor genes in antipsychotic-induced weight gain. A total of 206 patients (139 of European descent and 56 African Americans) who underwent treatment for chronic schizophrenia or schizoaffective disorder were evaluated after on average over 6 weeks of treatment. Thirty-six tag single nucleotide polymorphisms (SNPs) and one variable-number tandem repeat, spanning the five dopamine receptor genes (DRD1-DRD5) were analyzed. In the total sample, we found a nominally significant association between the DRD2 rs1079598 marker and weight change using a cutoff of 7% gain (P=0.03). When stratifying the sample according to ethnicity and antipsychotics with highest risk for weight gain, we found significant associations in three DRD2 SNPs: rs6277 (C957T), rs1079598 and rs1800497 (TaqIA). The other genes were primarily negative. We provide evidence that dopamine receptor DRD2 gene variants might be associated with antipsychotic-induced weight gain in chronic schizophrenia patients.
Müller
D J
DJ
Neurogenetics Section, Neuroscience Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Daniel_Mueller@camh.net
Zai
C C
CC
Sicard
M
M
Remington
E
E
Souza
R P
RP
Tiwari
A K
AK
Hwang
R
R
Likhodi
O
O
Shaikh
S
S
Freeman
N
N
Arenovich
T
T
Heinz
A
A
Meltzer
H Y
HY
Lieberman
J A
JA
Kennedy
J L
JL
D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D017931:DNA Primers; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011618:Psychotic Disorders / Q000188:drug therapy*; D011954:Receptors, Dopamine / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy*; D015430:Weight Gain
D014150:Antipsychotic Agents; D017931:DNA Primers; D011954:Receptors, Dopamine