No association between dopamine D(2) and D(4) receptor gene variants and antidepressant activity of two selective serotonin reuptake inhibitors.
The possible association of the dopamine receptor D(2) (Ser 311Cys) and D(4) exon 3 (48 base pair repeat) gene variants with the antidepressant activity of selective serotonin reuptake inhibitors (SSRIs) was investigated in a sample of 364 inpatients affected by a major depressive episode treated with fluvoxamine, 300 mg/day (n=266), or paroxetine, 20-40 mg/day (n=98). The severity of depressive symptoms was assessed weekly with the Hamilton Rating Scale for Depression. Dopamine receptor D(2) (DRD2) and dopamine receptor D(4) (DRD4) allelic variants were determined in each subject by polymerase chain reaction. We observed that DRD2 and DRD4 variants were not associated with response to SSRI treatment. Possible stratification factors, such as sex, diagnosis, presence of psychotic features, depressive symptoms at baseline, paroxetine and fluvoxamine plasma levels, and pindolol augmentation did not significantly influence the observed results. The investigated DRD2 and DRD4 gene variants therefore do not seem to play a major role in the antidepressant activity of SSRIs, at least in the present sample.
Serretti
A
A
Department of Psychiatry, Istituto Scientifico H San Raffaele, Vita-Salute University, Via Stamira D'Ancona 20, 20127 Milan, Italy. serretti.alessandro@hsr.it
Zanardi
R
R
Cusin
C
C
Rossini
D
D
Lilli
R
R
Lorenzi
C
C
Lattuada
E
E
Smeraldi
E
E
D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005091:Exons / Q000502:physiology; D005260:Female; D016666:Fluvoxamine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015870:Gene Expression / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D050638:Receptors, Dopamine D4; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use
D016666:Fluvoxamine; D017374:Paroxetine; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4; D017367:Selective Serotonin Reuptake Inhibitors; C493599:DRD4 protein, human