DOPAMINE RECEPTOR D2 (DRD2) IN PERIPHERAL BLOOD LYMPHOCYTES AS BIOMARKER OF RESPONSE TO ANTIPSYCHOTIC MEDICATION

Introduction. Despite the evolution of antipsychotic drugs, the problem of the therapy effectiveness and safety of schizophrenia spectrum disorders and comorbid conditions is very acute. The dopamine receptor D2 gene (DRD2) is one of the key targets of modern pharmacogenetic studies of mental disorders.

The objective of the study was to analyze the DRD2 mRNA level in peripheral blood lymphocytes and to identify genetic variations of –141С Ins/Del as potential biomarkers for antipsychotic therapy prognosis.

Methods and materials. The study included 112 patients with mental disorders: 61 – with a diagnosis of schizophrenia spectrum disorder, 51 – with a comorbid disease course with alcohol dependence syndrome, and 112 people as a control group. Psychometric evaluation was carried out using PANSS scale. The material was peripheral blood lymphocytes (PBLs). The DRD2 mRNA level was determined by real-time polymerase chain reaction with TaqMan probe. Genotyping –141С Ins/Del was performed by the restriction fragment length polymorphism assay.

Results. –141C Ins/Del DRD2 genetic variations are not associated with a risk of mental disorder development, and they did not affect the DRD2 mRNA level in PBLs. There were no significant differences in the gene expression of DRD2 in the control group and patients (p=0.194). Despite the improvement of the mental state in all patients included in the study, the studied DRD2 parameters did not affect either the mental disorder symptoms or the normalization of the patient status against the background of antipsychotic therapy. Ins/Ins genetic variation of –141C Ins/Del was significantly associated with an increase weight gain of more than 7 % on the 28th day of antipsychotic therapy.

Conclusion. Ins/Ins genetic variation of –141C Ins/Del can be considered as a biomarker for the prognosis of antipsychotic-induced weight gain. 

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