Neurohumoral markers that predict the efficiency of pharmacologic therapy of depressive disorders

We present a comprehensive clinical and biological study of 46 patients with depressive disorder (F32-F33: depressive episode and recurrent depressive disorder) during pharmacotherapy. Neurohumoral factors (cortisol, brain-derived neurotrophic factor, serotonin, DHEA and its sulfated form) were determined in serum by ELISA. The severity of the current depressive episode was evaluated using the 17-point Hamilton Depression Rating Scale (HDRS-17); the pharmacotherapy efficacy was evaluated using the scale of the Clinical Global Impression (CGI Scale). We showed that before prescription of pharmacotherapy peripheral blood neurohumoral markers that characterize the state of stress-realizing and stress-limiting systems of the body may be considered as biological predictors of the effective pharmacotherapy of a current depressive episode and used as additional paraclinical examination methods. At higher concentrations of cortisol and serotonin associated with a decrease in the content of neurosteroid dehydroepiandrosterone, the high efficiency of the pharmacotherapy of depressive episode is predicted

LED-technologies for bright light therapy

The significance of the LED-based medical equipment design is caused by the need to make up for the sunshine shortfall in many areas of Russia (Siberia, the Far East, the Extreme North) that will allow reducing dramatically the risk of seasonal affective disorders. The sunshine is the essential synchronizer of the human biological rhythms, the abnormality of which plays an important role in the seasonal affective disorder nature. The study allows proving the object database development able to meet the human demand for a comfortable and high-quality placemaking as well as the health potential recoverability

A new paradigm to indicate antidepressant treatments

This article develops the idea that clinical depression can be seen as a typical human response, largely rooted in human culture, to events of loss or times of adversity. Various biological, psychological, and social factors may cause some individuals to have a depressive reaction that is ineffectually limited in time and/or severity. Recovery occurs mainly based on natural resilience mechanisms, which come into play spontaneously, but which are sometimes inhibited or blocked by specific pathological biopsychosocial mechanisms. One of the mechanisms for this could be the influence of the circuits that regulate pleasure and happiness, along the dorsal diencephalic connection (DDC) pathway from the forebrain to the midbrain via the habenula. Therapy works by undermining the biopsychosocial factors that prevent the natural recovery mechanism from working. Treatment should, therefore, be seen as facilitating rather than causing natural recovery. This approach is in line with the high recovery rate after placebo treatments and the positive influence of pharmacological treatments with completely different sites of action. Acceptance of this model means that when studying new treatments for depression, a new paradigm must be applied in which the relative value of antidepressant treatment is specifically weighted in terms of enabling the natural resilience process

Polymorphisms in the adrenergic neurotransmission pathway impact antidepressant response in depressed patients

Mood disorders are a prevalent mental health disorder. The adrenergic neurotransmission pathway presents an opportunity to determine whether genetic mutations impact antidepressant response. For this study, 163 patients with major depressive disorders were enrolled to measure treatment response using the Hamilton Depression Rating Scale (HAMD-17). More than half of the patients had never been treated with antidepressants previously. Patients were genotyped for 14 SNPs within ADRA1A, SLC6A2, ADRβ1, MAOA and COMT to determine the impact of adrenergic neurotransmission polymorphisms related in antidepressant response. Patients were treated mainly with SSRIs and TCAs. The difference in HAMD-17 scores between the measurement periods were defined as the outcome measure. Multiple linear regression was conducted to determine the association between the genotypes and difference in HAMD-17 across the study period. Covariates of age, sex, antidepressant medication and depression diagnoses were included in the regression. Throughout the study HAMD-17 scores were measured at initiation, at two weeks and at four weeks for each patient. The difference in HAMD-17 scores was found to be 11.2 ​± ​4.4 between initiation and two weeks, 7.8 ​± ​5.3 between two week and four week, and 19.0 ​± ​5.3 throughout the entire study. SLC6A2 rs1532701 homozygous G/G Patients were associated with improved ΔHAMD-17 across week 2–4 and the entire study (B ​= ​7.1, p ​= ​0.002; B ​= ​6.7, p ​= ​0.013) compared to homozygous A/A patients. SLC6A2 rs1532701 homozygous A/G patients were further associated with improved ΔHAMD-17 compared to homozygous A/A patients at week 2–4 (B ​= ​2.8, p ​= ​0.023). Through our investigation, we were able to determine the genes within the adrenergic pathway to investigate further. To further elucidate these findings, replication and combination with other neurotransmitter pathways to better map the mechanism of actions of antidepressant for tailored treatment would be suggested

Preliminary pharmacogenetic study to explore putative dopaminergic mechanisms of antidepressant action

Background: There is sufficient evidence that interference of dopaminergic neurotransmission contributes to the therapeutic effects of antidepressants in unipolar and bipolar depression. Methods: Hamilton depression rating scale (HAMD 17) scores of 163 at least moderately ill patients with major depressive disorders were used to establish treatment response. HAMD 17 score status was measured before initiation, after two weeks, and after four weeks of treatment with various antidepressants. The possible association between response and genotype in a total of 14 variants of dopamine neurotransmission-related proteins was investigated. Results: DRD4 rs11246226 CA heterozygous patients were found with a greater improvement of HAMD 17 score when compared to homozygous C patients during 0–2 weeks and 0–4 weeks. Patients with MAOB rs1799836 heterozygous GA and homozygous A also demonstrated improved scores during 2–4 weeks and 0–4 weeks. Conclusions: The results are preliminary due to the limited population size and the small number of variants. Further research into the involvement of habenular dopamine D4 receptors in the antidepressant response is desirable

Депрессивные расстройства у женщин в климактерическом возрасте (обзор зарубежной литературы за 2012–2016 гг.)

Objective: to systematically review foreign literature and interpret results of the review. Tasks: to review foreign papers where factors are considered which provoke development of depression: hormonal, psychological, social as well as neuromediators, hormonal and immune disturbances in depressive disorders in women with physiological climacteric and climacteric syndrome; issues of differential diagnostics of depressions, psychopharmaco- and psychotherapy with subsequent evaluation of clinical efficiency; personality profile of pateints with affective psychopathology.Methods of search: by keywords in Web of Science Core Collection database across foreign journals (2012– 2016). Criteria of inclusion of papers in the review are determined by themes of studies: 1) women of climacteric age; 2) presence of depression or depressive symptoms; 3) presence of climacteric disturbances. In the abstract-bibliographic and scientometric database Web of Science Core Collection 70 bibliographic sources are selected across foreign journals between 2012 and 2016, including journals with high Impact Factor. Studies included in the review are performed at the university clinics, specialized centers. Clinical and sociodemographic characteristics of female patients meet the criterion of compatibility. Most discussed papers are devoted to study of clinical and social-psychological factors of development of climacteric depression. In a number of papers the efficiency of antidepressant therapy, alternative methods and supplementary therapy in women with depressive disorders, climacteric disturbances and co-occurring physical diseases is shown. Most works are performed with involvement of questionnaires (sociodemographic data, anamnesis) and international clinical scales. The main results of the discussed papers are outlined in thematic rubrics.Conclusion. The European and American papers are used in this review more frequently; studies from Asian countries are used more seldom. Reviewed foreign publications reflect worldwide trend to increase of climacteric depression (CD) in the female population with presence in the anamnesis of adolescent (psychoendocrine alteration) and postpartum depression, premenstrual syndrome. Low timely diagnostics of depressions, high incidence rate of somaticized CD are noted. In the structure of climacteric syndrome the psychoemotional disturbances predominate above neurovegetative and metabolic-endocrine or are combined with vegetative dysfunction. The participation in formation of CD (with predominance of mild/moderate severity) of neurohormonal, genetic, biochemical, social-environmental, psychological factors is shown. In the reviewed sources low mood, loss of previous priorities, decrease of productivity and concentration of attention, position of being unprotected, dependence, lack of confidence, self-humiliation, repentance, unbelief in future, insomnias, hypo-/hyperrexia with change of body mass are described in CD but there are no publications on suicidal ideation. It is indicated that CD can flow with hysteric- and nosophobic, somatohypochondriac and asthenohypochondriac component. The authors consider that somatization as an experience of climacteric stress leads to somaticized CD with accent on physical symptoms and repression of depression and anxiety although an association of specific somatic nosologies with symptoms of CD is not described. The association of CD with social-environmental factors (gender, education, profession, social position, financial wealth) is discussed, achievement of the woman is considered as a actor of reduction of CD risk. The authors are highly interested in search for genetic markers (heredity, suicides in relatives), impairment of neuromediator exchange (neurotransmitters serotonin, dopamine, adrenaline, and noradrenaline), neuromorphologic alterations in brain sensorimotor cortex (motor function, attention, perception, memory, and emotional-motivational response), hormonal disturbances (neuroendocrine and metabolic) and psychoneuroimmunological patterns of association with CD. Psychopharmacotherapy in CD is constructed with account for depressive symptoms (antidepressants of activating/sedative action in long-term maintenance regime), background and co-occurring diseases (adequate and pathogenetic and immunotherapy) with involvement in case of absence of contraindications of substitutive hormonotherapy (estrogen, progesterone). Beyond conventional schemes of the therapy the alternative therapy of CD (acupuncture, yoga, phytoestrogen collections, and food additives) is discussed. For heightening the efficiency and safety of the therapy of CD the training in detection of CD signs both for female patients and nurses, psychologists, social workers is proposed. Цель: обзор зарубежной периодики с интерпретацией результатов.Задачи: обзор зарубежных работ, в которых рассматриваются провоцирующие развитие депрессии факторы: гормональный, психологический, социальный, а также нейромедиаторные, гормональные и иммунные нарушения при депрессивных расстройствах у женщин с физиологическим климактерием и климактерическим синдромом; дифференциальная диагностика, психофармако- и психотерапия депрессий с оценкой клинической эффективности; личностный профиль пациентов с аффективной психопатологией.Методы поиска: по ключевым словам в базе данных Web of Science Core Collection по зарубежным журналам (2012–2016 гг.).Критерии включения статей в обзор: 1) женщины климактерического возраста; 2) депрессии или депрессивные симптомы; 3) климактерические нарушения. В реферативно-библиографической наукометрической базе Web of Science Core Collection по зарубежным журналам, в том числе с высоким импакт-фактором, выбрано 70 библиографических источников. Вошедшие в обзор исследования выполнены в университетских клиниках, специализированных центрах. Клинические и социально-демографические характеристики отвечают критерию сопоставимости. Большинство работ посвящено изучению клинических и социально-психологических факторов развития климактерической депрессии (КД). В ряде работ показана эффективность антидепрессивной терапии, альтернативных методов, дополнительного лечения у женщин с депрессивными расстройствами, климактерическими нарушениями и сопутствующими соматическими заболеваниями. Преобладают исследования, выполненные с привлечением анкетного опроса (социально-демографические данные, анамнез) и международных клинических шкал. Основные результаты обсуждаемых статей изложены в тематических рубриках.Заключение. С большей частотой встречаются европейские и американские работы, реже – из стран Азии. Публикации отражают мировую тенденцию к росту КД в женской популяции с наличием в анамнезе депрессии подростковой и послеродовой, предменструального синдрома. Отмечаются низкая своевременная диагностика депрессий, высокая встречаемость соматизированной КД. В структуре климактерического синдрома психоэмоциональные нарушения преобладают над нейровегетативными и обменно-эндокринными либо сочетаются с вегетативной дисфункцией. В формировании КД участвуют нейрогормональные, генетические, биохимические, социально-средовые, психологические факторы. При КД описаны угнетенное настроение, утрата жизненных приоритетов, снижение работоспособности и концентрации внимания, незащищенность, несамостоятельность, неуверенность, самоуничижение, раскаяние, неверие в будущее, инсомнии, гипо- и гиперрексия, но отсутствуют публикации по суицидальной настроенности. КД может протекать с истеро- и нозофобическим, соматоипохондрическим или астеноневротическим компонентом. Соматизация как переживание климактерического стресса приводит к соматизированной КД с акцентом на соматические симптомы и вытеснением депрессии и тревоги, хотя не описано ассоциированности конкретных соматических нозологий с КД. Обсуждается связь КД с социально-средовыми факторами (пол, образование, профессия, положение, финансовая состоятельность). Интерес авторов в развитии КД вызывает поиск генетических маркеров, нарушения нейромедиаторного обмена, нейроморфологические изменения в сенсомоторной коре головного мозга, гормональные и психонейроиммунологические нарушения. Психофармакотерапия при КД учитывает депрессивную симптоматику (антидепрессанты активизирующего и (или) седативного действия в длительном режиме), сопутствующие заболевания (патогенетическая и иммунотерапия, заместительная гормонотерапия эстрогеном, прогестероном). Обсуждается альтернативное лечение КД. Для повышения эффективности и безопасности лечения КД предлагается научение распознаванию признаков КД самих пациентов, медицинских работников, психологов, социальных работников.

Limited Associations Between 5-HT Receptor Gene Polymorphisms and Treatment Response in Antidepressant Treatment-Free Patients With Depression

Major depressive disorder has become a prominent cause of disability, as lifetime prevalence has increased to similar to 15% in the Western world. Pharmacological effects of serotonin (5-hydroxytryptamine, 5-HT) are mediated through 5-hydroxytryptamine receptor (5-HTR) binding. Serotonin regulation of amygdala activity is attained through activation of three 5-HT2 family receptor subtypes, 5-HT2A, 5-HT2B, and 5-HT2C. Specifically, HT2A and the HT2C receptors have similar gross cerebral distribution and function, with higher constitutive activity found in HT2C than in HT2A. We investigated the possible association of 5-HTR gene polymorphisms to specific and non-specific antidepressant treatment responses in treatment-free patients in Siberia. 156 patients, aged between 18-70 years and clinically diagnosed with depressive disorders, were treated with antidepressants for 4 weeks. Patients were genotyped for a subset of 29 SNPs from the following 5-HT Receptor genes: HTR1A, HTR1B, HTR2A, HTR2C, HTR3A, HTR3B and HTR6. Primary outcome was measured by differences in Hamilton Depression Rating Scale (Delta HAM-D 17) scores between baseline/week two, week two/week four and baseline/week four. Univariate linear regression was initially conducted to determine the 5-HTR SNPs to be studied within the multiple linear regression. Multiple linear regression analyses over the three time periods were conducted for Delta HAM-D 17 with independent factors including: age, gender, depression diagnosis, antidepressant treatment and selected 5-HTR SNPs. We found improved increment HAM-D 17 in patients taking tricyclic antidepressants (0-4 weeks: B = 4.85, p = 0.0002; 0-2 weeks: B = 3.58, p = 0.002) compared to patients taking SSRIs. Over the course of study, significant associations between 5-HT receptors SNPs and antidepressant response were not identified