Genetic Biomarkers of Antipsychotic-Induced Prolongation of the QT Interval in Patients with Schizophrenia

Antipsychotics (AP) induced prolongation of the QT interval in patients with schizophrenia (Sch) is an actual interdisciplinary problem as it increases the risk of sudden death syndrome. Long QT syndrome (LQTS) as a cardiac adverse drug reaction is a multifactorial symptomatic disorder, the development of which is influenced by modifying factors (APs’ dose, duration of APs therapy, APs polytherapy, and monotherapy, etc.) and non-modifying factors (genetic predisposition, gender, age, etc.). The genetic predisposition to AP-induced LQTS may be due to several causes, including causal mutations in the genes responsible for monoheme forms of LQTS, single nucleotide variants (SNVs) of the candidate genes encoding voltage-dependent ion channels expressed both in the brain and in the heart, and SNVs of candidate genes encoding key enzymes of APs metabolism. This narrative review summarizes the results of genetic studies on AP-induced LQTS and proposes a new personalized approach to assessing the risk of its development (low, moderate, high). We recommend implementation in protocols of primary diagnosis of AP-induced LQTS and medication dispensary additional observations of the risk category of patients receiving APs, deoxyribonucleic acid profiling, regular electrocardiogram monitoring, and regular therapeutic drug monitoring of the blood APs levels.

Vaiman Elena E.2 , Shnayder Natalia A.2, 3 , Zhuravlev Nikita M.2 , Petrova Marina M.3 , Asadullin Azat R.4 , Al-Zamil Mustafa 1 , Garganeeva Natalia P.5 , Shipulin German A.6 , Cumming Paul6, 8 , Nasyrova Regina F.2, 9
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  • 1 Российский университет дружбы народов
  • 2 Institute of Personalized Psychiatry and Neurology, V. M. Bekhterev National Medical Research Centre for Psychiatry and Neurology, 192019 Saint Petersburg, Russia
  • 3 Shared Core Facilities “Molecular and Cell Technologies”, V. F. Voyno-Yasenetsky Krasnoyarsk State Medical University, 660022 Krasnoyarsk, Russia
  • 4 Department of Psychiatry and Addiction, Bashkir State Medical University, 450008 Ufa, Russia
  • 5 Department of General Medical Practice and Outpatient Therapy, Siberian State Medical University, 634050 Tomsk, Russia
  • 6 Centre for Strategic Planning and Management of Biomedical Health Risks Management, 119121 Moscow, Russia
  • 7 Department of Nuclear Medicine, Bern University Hospital, 3010 Bern, Switzerland
  • 8 School of Psychology and Counselling, Queensland University of Technology, Brisbane 4000, Australia
  • 9 International Centre for Education and Research in Neuropsychiatry, Samara State Medical University, 443016 Samara, Russia
Ключевые слова
schizophrenia; antipsychotics; adverse drug reaction; antipsychotic-induced repolarization disorder; cardiac repolarization; long QT interval; sudden death syndrome; ventricular tachyarrhythmia; pharmacogenetics
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