Связь полиморфизма генов СОМТ, DRD2/ANKK1, MTHFR, MIR137, DNMT3B с клиническими проявлениями шизофрении в остром периоде и в состоянии ремиссии

Updated view of genetic features of schizophrenia based on rare SNPs/CNVs with a huge influence on a disease and common SNPs with a small effect of each allele is presented. Altogether these genetic factors are acting to create neuropathophysiological disturbances observed in schizophrenia. Association of five polymorphisms MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133, DNMT3B rs2424913, СОМТ rs4680 with the risk of schizophrenia in the Belarusian population, the level of symptoms of schizophrenia patients assessed by PANSS in the acute stage and remission, cognitive impairments, and treatment trajectory of schizophrenia patients during antipsychotic treatment were analyzed. The A/A-genotype of СОМТ rs4680 (р = 0.008) and the С/С-genotype of MTHFR rs1801133 (р = 0.02) are associated with the risk of schizophrenia among Belarusians. The T-allele of MTHFR rs1801133 is a risk factor of positive symptoms (р = 0.02). Combining the C/C-genotype (DNMT3B rs2424913) and the G-allele (COMT rs4680) is associated with a significant difference in negative symptoms level between men and women. The polymorphism of СОМТ rs4680 (р < 0.05) and the combination of СОМТ rs4680 + DRD2/ANKK1 rs1800497 (р = 0.005) as well as MTHFR rs1801133 + DNMT3B rs2424913 (р = 0.006) are related to the cognitive parameters measured by the WCST and Stroop test respectively. Schizophrenia patients who are the G-allele carriers of MIR137 rs1625579 demonstrated a more favorable negative symptom trajectory in comparison to Т/Тhomozygotes (F = 2.2, p = 0.03). The trajectory of negative symptoms (F = 2.2, p = 0.03) and general psychopathological symptoms (F = 4.3, p = 0.0001) is different between men and women under antipsychotic treatment. These differences are associated with a minor amount of alleles of MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133 polymorphic sites.По современным представлениям, пациент, страдающий шизофренией, является, как правило, носителем одной или нескольких редких аллелей с высоким эффектом и ряда распространенных аллелей с малыми эффектами. Совместное действие генетических факторов реализуется определенными нейробиологическими путями, которые порождают спектр нейрофизиологических нарушений, наблюдаемых при шизофрении. В ходе исследования была проанализирована связь полиморфных сайтов MIR137 rs1625579, DRD2/ANKK1 rs1800497, MTHFR rs1801133, DNMT3B rs2424913, СОМТ rs4680 с риском возникновения шизофрении среди белорусов, степенью выраженности симптомов по шкале PANSS в остром периоде и в фазе ремиссии, когнитивными нарушениями и динамикой изменения симптоматической картины пациентов с шизофренией в период поддерживающей терапии антипсихотиками. Согласно полученным результатам, генотип A/AСОМТ rs4680 (р = 0,008) и генотип С/С MTHFR rs1801133 (р = 0,02) являются факторами риска развития шизофрении среди мужчин белорусской популяции. Выявлены множественные связи исследуемых локусов с различными видами симптомов и когнитивными параметрами. T-аллель MTHFR rs1801133 связан с риском формирования психотических симптомов (р = 0,02). Сочетание генотипа C/C (DNMT3B rs2424913) и G-аллеля (COMT rs4680) связано со значимыми различиями в уровне негативных симптомов между пациентами мужского и женского пола (p = 0,00009). Наиболее выражена связь локуса СОМТ rs4680 (р < 0,05) и комбинации локусов СОМТ rs4680 + DRD2/ANKK1 rs1800497 (р = 0,005) с когнитивными параметрами (оценка по Висконсинскому тесту сортировки карточек – ВТСК), а также комбинации локусов MTHFR rs1801133 + DNMT3B rs24 24913 (р = 0,006) с параметром теста Струпа. Также обнаружено, что пациенты с G-аллелем MIR137 rs1625579 демонстрируют более благоприятную динамику изменения негативной симптоматики (F = 2,2, p = 0,03) в сравнении с Т/Тгомозиготами. Обнаружены достоверные различия в траектории изменения негативной (F = 2,2, p = 0,03) и общей психопатологической симптоматики (F = 4,3, p = 0,0001) в период терапии между пациентами мужского и женского пола в зависимости от количества минорных аллелей по исследуемым полиморфным вариантам

Compulsory admissions of patients with mental disorders : State of the art on ethical and legislative aspects in 40 European countries

Background. Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. Methods. The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. Results. We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. Conclusions. We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.Peer reviewe

Compulsory admissions of patients with mental disorders: State of the art on ethical and legislative aspects in 40 European countries

BACKGROUND: Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care. METHODS: The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions. RESULTS: We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures. CONCLUSIONS: We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions