Association of dopaminergic and serotonergic genes with tardive dyskinesia in patients with chronic schizophrenia.
Tardive dyskinesia (TD) is a long-term adverse effect of antipsychotic drugs that are dopamine D2 receptor blockers. Serotonin receptor antagonism has been proposed as a common mechanism contributing to the low extrapyramidal side effect profile of atypical antipsychotic drugs. We evaluated candidate dopamine and serotonin genes for association with drug-induced TD. We examined three polymorphisms in the dopamine D2 receptor gene (DRD2), two sites in the 3' region of the dopamine transporter (DAT) gene, two sites in the promoter and coding region of the dopamine D4 (DRD4) receptor gene, as well as polymorphic sites in the serotonin 6 receptor gene, the serotonin transporter gene and the tryptophan hydroxylase gene, for association with TD susceptibility. Schizophrenic patients with (n=59) and without TD (n=63), matched for antipsychotic drug exposure and other relevant variables, were studied. No significant associations were found. Within the limitations imposed by the size of the clinical sample, these findings suggest that the above polymorphic loci do not contribute significantly to risk for TD. Further examination of loci that yielded positive results at a trend level and investigation of other candidate genetic loci coding for antipsychotic drug targets is warranted.
Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah Hebrew University Medical Center, Jerusalem, Israel. sronen@md2.huji.ac.il
R H
RH
Segman
T
T
Goltser
U
U
Heresco-Levy
B
B
Finkel
R
R
Shalem
M
M
Schlafman
A
A
Yakir
D
D
Greenberg
R
R
Strous
A
A
Lerner
A
A
Shelevoy
B
B
Lerer
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects; D016009:Chi-Square Distribution; D004298:Dopamine / Q000235:genetics*; D004409:Dyskinesia, Drug-Induced / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics*; D012701:Serotonin / Q000235:genetics*
D014150:Antipsychotic Agents; D012701:Serotonin; D004298:Dopamine