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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.

Background: Brain-derived neurotrophic factor (BDNF) is associated with response to antidepressant drugs in mood and anxiety disorders. Prolactin (PRL) is a pituitary hormone with behavioural effects, acting as a neurotrophic factor within the brain and may be involved in antidepressant response.Objectives: To investigate the relationship between BDNF and PRL genotypes with antidepressant drug response.Methods: Prospective inception cohort of 186 Russian treatment-free participants (28 men and 158 women) between 18 and 70 years clinically diagnosed with depressive disorder who initiated antidepressant medication. DNA polymorphisms were genotyped for PRL rs1341239, BDNF rs6265 and rs7124442. Primary outcome was measured by differences in Hamilton Depression Rating Scale (Delta HAM-D) scores between baseline/week two, week two/week four, and baseline/week four. Linear regression and independent t-test determined the significance between polymorphisms and Delta HAM-D.Results: Comparisons between genotypes did not reveal any significant differences in scores during the first two weeks of treatment. In the latter two weeks, BDNF rs7124442 homozygous C patients responded significantly worse in comparison to homozygous T patients during this period. Further analysis within women and in postmenopausal women found a similar comparison between alleles.Limitations: Study lasted four weeks, which may be considered short to associate genuine antidepressant effects.Conclusions: Patients taking tricylic antidepressants were noted to have a significant improvement in Delta HAM-D compared to patients taking SSRIs. Homozygous C BDNF rs712442 patients were found to respond significantly worse in the last two weeks of treatment.

Background Many antidepressants are substrates of P-glycoprotein, an efflux transporter in the blood-brain-barrier encoded by the ABCB1 gene. Genetic variations might influence the transport rate of antidepressants and hence their pharmacological effects. This study investigates the influence of eight polymorphisms in the ABCB1 gene on antidepressant treatment response. Method 152 patients were included from psychiatric departments of the Mental Health Research Institute in Tomsk. The difference in Hamilton-Depression-Rating-Scale (HAMD-17)-scores between baseline and week two, week two and four, and baseline and week four was used to estimate timing of improvement of depression. Associations between the ABCB1 gene-polymorphisms and reduction in HAMD-17 score were assessed using independent t-test and multiple linear regression. Results Tricyclic antidepressants were associated with a higher reduction of HAMD-17 score when compared to SSRIs. The SNP rs2235040 A-allele had a significant positive influence on the Delta HAMD-17((0 -> 2W)) score but a significant negative influence on the Delta HAMD-17((2 -> 4W)) score. The rs4148739 G-allele had a significant negative influence on the Delta HAMD-17((0 -> 2W)) score but a significant positive influence on the Delta HAMD-17((2 -> 4W)) score. The SNP rs2235015 T-allele is significant negatively related to the Delta HAMD-17((2 -> 4W)) score. Conclusion ABCB1 Genetic variations appear to affect speed but not magnitude of antidepressant drug response.

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.

OBJECTIVE: AKT1 and GSK3B take part in one of the intracellular cascades activated by the D2 dopamine receptor (DRD2). This receptor is antagonized by antipsychotics and plays a role in the pathogenesis of antipsychotic-induced tardive dyskinesia (TD). The present study investigated association of several polymorphisms in the two candidate genes, AKT1 and GSK3B, with TD in antipsychotic-treated patients with schizophrenia.METHODS: DNA samples from 449 patients from several Siberian regions (Russia) were genotyped, and the results were analyzed using chi-squared tests and analyses of variance.RESULTS: Antipsychotic-induced TD was not associated with either of the tested functional polymorphisms (rs334558, rs1130214, and rs3730358).CONCLUSIONS: Despite regulation of AKT1 and GSK3B by DRD2, we found no evidence that these two kinases play a major role in the pathogenesis of antipsychotic-induced TD. These results agree with previously published data and necessitate further exploration of other pathogenic mechanisms, such as neurotoxicity due to excessive dopamine metabolism.

Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

To study the association between polymorphisms of PIP5K2A and HTR2C genes and response to antidepressant therapy in patients with a current depressive episode.The study included 222 patients (168 women and 54 men) with a current depressive episode. The assessment of the severity of the current depressive episode and the efficacy of treatment was performed using the Hamilton depression scale (HDRS-17) and the Clinical global impression scale (CGI-S, CGI-I). The association of treatment efficacy with PIP5K2A polymorphisms rs10430590, rs10828317 and HTR2C polymorphisms rs6318, rs569959, rs3813929, rs12858300 was studied.Polymorphisms rs10828317 and rs10430590 in the PIP5K2A gene were associated with the CGI-S total score at day 28 of therapy. Polymorphism rs6318 in the HTR2C gene was associated with response to antidepressant therapy followed by clinical improvement of patients with current depressive episode on the 28th day of antidepressant therapy.Цель исследования - выявление ассоциаций полиморфных вариантов гена PIP5K2A киназы и гена HTR2C рецептора 2С серотонина с эффективностью терапии текущего депрессивного эпизода. Материал и методы. Обследованы 222 пациента, 168 женщин и 54 мужчины, с текущим депрессивным эпизодом. Оценку тяжести текущего депрессивного эпизода и эффективности терапии проводили с применением шкал депрессии Гамильтона (HAM-D-17) и общего клинического впечатления (CGI-S) при поступлении в стационар, а также на 14-й и 28-й дни терапии. Оценивали ассоциации полиморфных вариантов генов PIP5K2A (rs10430590, rs10828317) и HTR2C (rs6318, rs569959, rs3813929, rs12858300) с эффективностью терапии текущего депрессивного эпизода. Результаты и заключение. Пациенты с депрессивным эпизодом с генотипом С/С по rs10828317 гена PIP5K2A имели более низкий балл по шкале CGI-S (1,64±0,64) на 28-й день терапии, чем пациенты с генотипами С/Т (2,23±0,96) и Т/Т (2,18±0,79) (р=0,038), а носители генотипа Т/Т по rs10430590 гена PIP5K2A - более низкие значения балла по шкале CGI-S (1,53±0,87) по сравнению с генотипами А/А (2,18±0,79) и А/Т (2,24±0,96) (р=0,043). У женщин rs3813929 ассоциирован с тяжестью текущего депрессивного эпизода, оцененной по шкале CGI-S до начала терапии (р=0,019), a rs6318 гена HTR2C ассоциирован с клиническим улучшением, оцененным по шкале Гамильтона, на 28-й день терапии (р=0,050).

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.

According modern biological hypotheses of the pathogenesis of affective disorders, hypothalamic–pituitary–adrenal axis dysfunction play a special role in the pathogenesis of this condition. Our study shows that the range of neuroprotective neurosteroids is gender- and nosology-dependent. Patients with affective disorders have reduced levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate; the most pronounced defi ciency of neuroprotective neurosteroids is typical of patients with a single depressive episode. Reduced levels of neurosteroids producing an anabolic effect probably indicate depletion of adaptive capacities of the hypothalamic–pituitary–adrenal system in affective disorders.

Spontaneous and induced apoptosis of neutrophils and lymphocytes was studied in alcoholics during the abstinent syndrome and in healthy individuals. In alcoholics, the levels of lymphocyte and neutrophil apoptosis at the receptor and cellular levels were higher than in healthy subjects. Blood cells from alcohol addicts and normal individuals similarly react to stimuli (hyperthermia and synthetic glucocorticoid prednisolone) in vitro.

Objectives. Nowadays it is considered that protein kinase Akt1 could be involved in pathogenesis of affective disorders. We have examined whether AKT1 gene polymorphisms are associated with antidepressant treatment response. Methods. The study included 106 Caucasian patients with depressive disorders from Siberia and 103 healthy control donors. The frequencies of single nucleotide polymorphisms rs1130214 and rs3730358 of AKT1 gene were examined. Results. A comparison of genotypic or allelic frequencies between the groups of healthy donors and depressive patients showed no statistically significant difference. No association between the polymorphisms under study and the scores according to Hamilton Depression Rating Scale 17 was found. However, an association between treatment response assessed by the Clinical Global Impression - Improvement scale and rs1130214 polymorphism was observed. Conclusions. AKT1 gene polymorphism rs1130214 is associated with antidepressant treatment response in patients with depressive disorders.