Association Between Period 3 Gene Polymorphisms and Adverse Effects of Antidepressants for Major Depressive Disorder

Circadian rhythm genes including Period 3 (Per3) are associated with major depressive disorder (MDD) and have an effect on the patient's response to selective serotonin reuptake inhibitor (SSRI) antidepressants. The aim of this study was to identify possible associations between three single nucleotide polymorphisms (SNPs) of Per3 (rs10746473, rs228697, and rs228729), the MDD symptoms, and adverse effects of SSRIs. A total of 600 MDD patients who had been treated with SSRIs were enrolled. The 17-item Hamilton Rating Scale for Depression (HAMD₁₇) was used to evaluate symptoms and treatment efficacy. In addition, the Treatment Emergent Symptom Scale/UKU Consumer Satisfaction Rating Scale (TESS/UKU) was used to assess adverse effects. The Per3 locus was genotyped by PCR and DNA sequencing. The Per3 rs228697 CC genotype was associated with a higher sleep factor score when compared with the CG genotype (F = 4.027, p = 0.046). In addition, the rs228729 TC genotype was associated with a greater risk of suffering from excitement/agitation (p = 0.002, OR [odds ratio] = 4.049), akathisia (p = 0.014, OR = 4.905) and weight loss (p = 0.041, OR = 2.287) when compared with the CC genotype. Finally, the rs10746473 AA genotype patients were more likely to suffer from dizziness (p = 0.042, OR = 0.362) and the GA genotype patients from tachycardia (p = 0.015, OR = 0.340) when compared with those with GG genotype. The Per3 gene variants in patients can predict adverse effects of SSRIs and drug compliance.