COMT and Neuregulin 1 Markers for Personalized Treatment of Schizophrenia Spectrum Disorders Treated with Risperidone Monotherapy

Pharmacogenetic markers are current targets for the personalized treatment of psychosis.Limited data exist on COMT and NRG1 polymorphisms in relation to risperidone treatment. Thisstudy focuses on the impact of COMT rs4680 and NRG1 (rs35753505, rs3924999) polymorphisms onrisperidone treatment in schizophrenia spectrum disorders (SSDs). This study included 103 subjectswith SSD treated with risperidone monotherapy. COMT rs4680, NRG1 rs35753505, and rs3924999were analyzed by RT-PCR. Participants were evaluated via the Positive and Negative Syndrome Scale(PANSS) after six weeks. Socio-demographic and clinical characteristics were collected. COMT rs4680genotypes significantly differed in PANSS N scores at admission: AG>AA genotypes (p= 0.03). Aftersix weeks of risperidone, PANSS G improvement was AA>GG (p= 0.05). The PANSS total score wasas follows: AA>AG (p= 0.04), AA>GG (p= 0.02). NRG1 rs35753504 genotypes significantly differedacross educational levels, with CC>CT (p= 0.02), and regarding the number of episodes, TT>CC,CT>CC (p= 0.01). The PANSS total score after six weeks of treatment showed a better improvementfor TT<CT genotypes (p= 0.01). NRG1 rs3924999 genotypes revealed GG<AG (p= 0.02) for PANSSG scores after six weeks, with AG and GG requiring higher doses (p= 0.007,p= 0.02). Overall, ourstudy suggests that the genetic polymorphisms COMT rs4680, NRG1 rs35753505, and rs3924999significantly impact the treatment response to risperidone in patients with SSD.