Association of the dopamine receptor interacting protein gene, NEF3, with early response to antipsychotic medication.
Genetic variation in antipsychotic drug targets could underlie variability among patients in the time required for antipsychotic effects to be elicited. In a clinical, pharmacogenetic study we focused on the dopamine receptor interacting protein (DRIP) gene family. DRIPs are pivotally involved in regulating dopamine receptor signal transduction. Consecutively hospitalized, acutely psychotic patients with DSM-IV schizophrenia (n=121) were included in the study if they received treatment with typical antipsychotic medication (TYP, n=72) or TYP plus risperidone (TYP-R, n=49) for at least 2 wk. Clinical state and adverse effects were rated at baseline and after 2 wk. Patients improved significantly on both TYP and TYP-R with no significant difference between them. Early responders were defined as patients whose PANSS change scores were greater than the median. Twenty-two single nucleotide polymorphisms (SNPs) were analysed in five DRIP-encoding genes. Two SNPs in NEF3, which encodes the DRIP, neurofilament-medium (NF-M), were associated with early response (rs1457266, p=0.01; rs1379357, p=0.006). A 5 SNP haplotype spanning NEF3 was over-represented in early responders (p=0.015), in the combined patient group and in the TYP group alone. These findings suggest that variation in NEF3, most likely functional variants that are in linkage disequilibrium with the SNPs that we studied, influences rate of response to TYP. Since NEF3 is primarily associated with dopamine D1 receptor function, the evidence for a complementary role of dopamine D1 receptors in antipsychotic effects is considered. The findings reported here open an interesting research avenue in the pharmacogenetics of antipsychotic effects but require replication in larger samples treated in a controlled context.
Strous
Rael D
RD
Beer Yaakov Mental Health Center, Beer Yaakov and Sackler Faculty of Medicine, Tel Aviv, Israel.
Greenbaum
Lior
L
Kanyas
Kyra
K
Merbl
Yifat
Y
Horowitz
Anat
A
Karni
Osnat
O
Viglin
Dina
D
Olender
Tsviya
T
Deshpande
Smita N
SN
Lancet
Doron
D
Ben-Asher
Edna
E
Lerer
Bernard
B
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018967:Risperidone / Q000009:adverse effects / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D016900:Neurofilament Proteins; C061195:neurofilament protein M; D018967:Risperidone