DRD2, 5-HT1A, and 5-HT2A gene polymorphisms and clinical factors modulate aripiprazole efficacy in different symptom dimensions of schizophrenia
Abstract
Objectives: Aripiprazole acts as a partial agonist at dopamine D2 and serotonin 1A (DRD2, and 5-HT1A) receptors, and as an antagonist at serotonin 2A (5-HT2A) receptors. The current study aims to examine the possible association between genetic variants (DRD2/ANKK1 Taq1A (rs1800497), 5-HT1A C-1019G (rs6295), and 5-HT2A T102C (rs6313) polymorphisms) and clinical factors on the therapeutic response to aripiprazole in Han Chinese hospitalized patients with acutely exacerbated schizophrenia.
Methods: After hospitalization, the patients (n=128) were given a 4-week course of aripiprazole. Patients were genotyped for the studied polymorphisms via the restriction fragment length polymorphism method. Clinical factors such as gender, age, duration of illness, and final medication dosage were noted as well. The researchers measured psychopathology biweekly, using the Positive and Negative Syndrome Scale (PANSS) five-factor model scale (positive, negative, excitement, cognitive, and depressive). A mixed model regression approach (SAS Proc MIXED) was used to analyze the effects of genetic and clinical factors on PANSS performance after aripiprazole treatment.
Results: We found that the A1/A1 (T/T) genotype of DRD2/ANKK1 Taq1A (rs1800497) polymorphism predicted superior aripiprazole treatment response specifically for positive and excitement symptoms. Otherwise, the T/T and T/C genotype groups of 5-HT2A T102C (rs6313) polymorphism predicted superior aripiprazole treatment response specifically for negative symptoms. Furthermore, the C/C genotype of 5-HT1A C-1019G (rs6295) polymorphism predicted superior aripiprazole treatment response specifically for cognitive and depressive symptoms. Finally, the clinical factors including dosage of aripiprazole and duration of illness were found to influence PANSS performance upon aripiprazole treatment.
Conclusions: Our study shows DRD2, 5-HT1A, and 5-HT2A gene polymorphisms and clinical factors modulate aripiprazole efficacy in different symptom dimensions of schizophrenia.
Keywords: rs1800497, rs6295, rs6313, aripiprazole, schizophrenia