Genome-wide research of antidepressant response has indicated that genes initially associated with risk for schizophrenia may also be promising candidates for selective serotonin reuptake inhibitor (SSRI) efficacy. Protein tyrosine phosphatase, receptor-type, zeta-1 (PTPRZ1) have shown an association with schizophrenia but is not investigated as a predictor of antidepressant efficacy. 

A recent study assessed if SSRI-mediated depressive and anxiety symptom remission in Chinese patients with major depressive disorder (MDD) is associated with specific PTPRZ1 variants.

The study investigated two independent cohorts, the first sample (N = 344) received an SSRI (i.e. fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, or paroxetine) for 8 weeks, while the second sample (N = 160) received only escitalopram for 8 weeks. Hamilton Depression and Hamilton Anxiety Rating Scale scores at 8 weeks post-baseline evaluated the remission status; and five PTPRZ1 subtypes (rs12154537, rs6466810, rs6466808, rs6955395, and rs1918031) were genotyped in both cohorts.

It was found that the anxiety symptom remission is robustly associated with PTPRZ1 rs12154537 and the G–G–G–G haplotype (rs12154537–rs6466810–rs6466808–rs6955395) in cohort 2 but not cohort 1. Associations with depressive symptom remission did not persist correction for multiple testing.

These findings suggest that PTPRZ1 variants can be used as a marker of escitalopram-mediated anxiety symptom remission in MDD.

Su Y-A, Bousman CA, Liu Q, et al. Anxiety symptom remission is associated with genetic variation of PTPRZ1 among patients with major depressive disorder treated with escitalopram. Pharmacogenetics and Genomics. 2021;31(8):172-176(5).