actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2019-4.2.5actabiomedica-2043Research ArticleГЕНЕТИКА, ПРОТЕОМИКА И МЕТАБОЛОМИКАGENETICS, PROTEOMICS AND METABOLOMICSФармакогенетика антидепрессантов: от генетических находок к предсказательным стратегиямPharmacogenetics of Antidepressants: from Genetic Findings to Predictive StrategiesХохловЛ. К.KhokhlovL. K.

Хохлов Леонид Константинович – доктор медицинских наук, профессор, профессор кафедры психиатрии

Leonid K. Khokhlov – Dr. Sc. (Med.), Professor, Professor of the Department of Psychiatry

ul. Revolyutsionnaya 5, Yaroslavl 150000

al460935@yandex.ruЛукьяновН. Е.LukyanovN. E.

Лукьянов Николай Евгеньевич – студент

150000, г. Ярославль, ул. Революционная, 5

Nikolay E. Lukyanov – Student

ul. Revolyutsionnaya 5, Yaroslavl 150000

lukianovnickhol@mail.ruФГБОУ ВО «Ярославский государственный медицинский университет» Минздрава РоссииYaroslavl State Medical University201923052019423343Copyright © Хохлов Л.К., Лукьянов Н.Е., 20192019Хохлов Л.К., Лукьянов Н.Е.Khokhlov L.K., Lukyanov N.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/2043

Постоянно растущий вклад депрессивных расстройств в глобальную картину заболеваний настоятельно требует повышения эффективности используемых для лечения препаратов и оптимизации терапевтических методов. Антидепрессанты являются наиболее часто назначаемыми препаратами для лечения депрессивных расстройств. Однако выработка стандартизованного фармакотерапевтического подхода осложняется генетической гетерогенностью и отсутствием надёжных биомаркеров для предсказания ответов на терапию, биологической вариабильностью метаболизма лекарств, а также множественными побочными эффектами препаратов. По современным оценкам, до 20 % экспрессируемых в нашем головном мозге генов так или иначе вовлечены в патогенез депрессии. Широкомасштабные генетические и геномные исследования выявили ряд потенциально прогностических генов. Также было показано, что эффективность и переносимость антидепрессантов напрямую зависят от вариабельности в активности ферментов, метаболизирующих медикаменты. Почти все современные антидепрессанты метаболизируются ферментами семейства цитохрома Р450 (семейство CYP). Наиболее многообещающим направлением исследований считается метод Полногеномного Поиска Ассоциаций (GWAS). Он направлен на детальное изучение ассоциаций между геномными вариациями и фенотипическими признаками. В исследованиях такого типа обычно сравнивают геномы депрессивных больных, имеющих разные фенотипы, с геномами контрольной группы, состоящей из аналогичных по возрасту, полу и другим признакам здоровых людей. Следует отметить, что, несмотря на анализ крупных когорт пациентов, в проведённых GWA-исследованиях пока не удаётся надёжно воспроизвести результаты других аналогичных исследований. Грандиозная гетерогенность определяющих развитие депрессии генов и их плейотропный эффект в сочетании с мощным влиянием факторов внешней среды объясняют сложность получения значимых и воспроизводимых результатов. Однако, несмотря на это, активная научная работа в разных направлениях позволяет клиницистам и их пациентам надеяться уже в ближайшие годы получить целый ряд схем скорейшего и гарантированного выхода в ремиссию.

The constantly growing contribution of depressive disorders to the global disease statistics calls for a growth of treatment effectiveness and optimization. Antidepressants are the most frequently prescribed medicines for depressive disorders. However, development of a standardized pharmacotherapeutic approach is burdened by the genomic heterogeneity, lack of reliable predictive biomarkers and variability of the medicines metabolism aggravated by multiple side effects of antidepressants. According to modern assessments up to 20 % of the genes expressed in our brain are involved in the pathogenesis of depression. Large-scale genetic and genomic research has found a number of potentially prognostic genes. It has also been proven that the effectiveness and tolerability of antidepressants directly depend on the variable activity of the enzymes that metabolize medicines. Almost all modern antidepressants are metabolized by the cytochrome P450 family enzymes. The most promising direction of research today is the GWAS (Genome-Wide Association Study) method that is aimed to link genomic variations with phenotypical manifestations. In this type of research genomes of depressive patients with different phenotypes are compared to the genomes of the control group containing same age, sex and other parameters healthy people. Notably, regardless of the large cohorts of patients analyzed, none of the GWA studies conducted so far can reliably reproduce the results of other analogous studies. The explicit heterogeneity of the genes associated with the depression pathogenesis and their pleiotropic effects are strongly influenced by environmental factors. This may explain the difficulty of obtaining clear and reproducible results. However, despite any negative circumstances, the active multidirectional research conducted today, raises the hope of clinicians and their patients to get a whole number of schedules how to achieve remission faster and with guaranteed results

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The authors declare that there are no conflicts of interest present.