[Association of anhedonia with comorbid mental disorders, suicidality and personality traits in patients with depression]. / Vzaimosvyaz' angedonii s komorbidnymi psikhicheskimi rasstroistvami, suitsidal'nost'yu i chertami lichnosti u patsientov s depressiei.

OBJECTIVE: A comprehensive assessment of anhedonia in patients with depression, considering their demographic, clinical and personality characteristics. MATERIAL AND METHODS: This cross-sectional, multicenter study included 190 patients with depression (63.7% women, mean age (Me) 31 (24-46.5) years) diagnosed with a depressive episode (F32) and recurrent depressive disorder (F33) according to the ICD criteria regardless of the disease stage (exacerbation or remission). Comorbid mental disorders of the anxiety spectrum, eating behavior, substance abuse, and psychotic symptoms were assessed and recorded. The Snaith-Hamilton Pleasure Scale (SHAPS) was used to assess the severity of anhedonia. RESULTS: Patients with an earlier onset of depression (p=0.037) and a history of suicide attempts (p=0.001) showed higher scores for anhedonia. The generalized anxiety disorder, panic disorder, bulimia nervosa, and alcohol dependence in patients with current depression were associated with higher anhedonia. The anhedonia scores had moderate positive correlations with a number of personality traits on TCI-125: Harm Avoidance (r=0.30; p<0.01), as well as weak negative correlations with Reward dependence (r= -0.20; p<0.05) and Cooperativeness (r= -0.26; p<0.05). There were also weak positive correlations of anhedonia scores with the severity of suicidal ideation and suicidal risk (for the last month and throughout life) and moderate positive correlations with the severity of suicidal behavior throughout life. CONCLUSIONS: The study confirms and expands the information about the complex nature of the anhedonia phenomenon in patients with depression. Further research on anhedonia may help in clinical practice and become the basis for the search for new biomarkers of depression.

[Comparative analysis of the effectiveness of SF-MPQ-2 and VAS for assessing the severity of pain syndrome in dental patients in the postoperative period]. / Sravnitel'nyi analiz effektivnosti oprosnika SF-MPQ-2 i vizual'noi analogovoi shkaly dlya otsenki vyrazhennosti bolevogo sindroma u stomatologicheskikh patsientov v posleoperatsionnom periode.

OBJECTIVE: Conducting a comparative analysis of the effectiveness of the Short-Form McGill Pain Questionnaire-2 (SF-MPQ-2) and the Visual Analogue Scale (VAS) for assessing the severity of pain syndrome in dental patients in the postoperative period in dynamics. MATERIAL AND METHODS: The study included 51 patients who received dental surgical treatment. Two groups of patients were formed, depending on the type of surgery and the degree of trauma of the operation. Group 1 - low degree of injury - 28 patients; group 2 - high degree of injury - 23 patients. Patients independently filled out questionnaires at four stages of the study: before surgery, on the 1st, 3rd, and 5th days after surgery as part of scheduled visits. RESULTS AND DISCUSSION: In patients of group 2, the severity of pain symptoms was higher than in patients of group 1 in terms of pain symptoms on SF-MPQ-2 at all stages of the study, except the day before surgery. At the same time, there were no differences with the indicators of the VAS scale at any of the stages of the study. The most informative indicators of SF-MPQ-2 are the total indicator MPQ-Sum and the constant pain indicator MPQ-Const, which were significantly higher in group 2 on the 1st day after surgery, taking into account the correction for gender and age. The highest level of coincidence of indicators on VAS and the total score on MPQ-Sum was revealed on the 5th day of the operation, regardless of the degree of trauma of the operation. CONCLUSION: The use of SF-MPQ-2 with a detailed description of pain sensations is the most acceptable way to assess the degree of pain syndrome in operative surgery, especially during the period when the severity of pain symptoms is maximum (in the first days of the postoperative period).

[Anhedonia in mood disorders and somatic diseases: results of exploratory Mendelian randomization analysis]. / Angedoniya pri rasstroistvakh nastroeniya i somaticheskikh zabolevaniyakh: rezul'taty razvedochnogo Mendelevskogo randomizatsionnogo analiza.

OBJECTIVE: To conduct an exploratory Mendelian randomization analysis of the causal relationships of anhedonia with a wide range of psychiatric and somatic phenotypes based on the genetic data of participants in a population study. MATERIAL AND METHODS: This cross-sectional study included 4520 participants, of which 50.4% (n=2280) were female. The mean age was 36.8 (S.D.=9.8) years. Participants were pheno-nailed based on the DSM-5 criteria for anhedonia in the framework of depression. An episode of anhedonia exceeding 2 weeks during life was reported by 57.6% (n=2604) of participants. A genome-wide association study (GWAS) of the anhedonia phenotype was performed, as well as a Mendelian randomization analysis using summary statistics of large-scale GWASs on psychiatric and somatic phenotypes. RESULTS: The GWAS on anhedonia did not reveal the variants with genome-wide significant association (p<10-8). The most significant (p=9.71×10-7) was the variant rs296009 (chr5:168513184) in an intron of the slit guidance ligand 3 (SLIT3) gene. Using Mendelian randomization, nominally significant (p<0.05) causal associations of anhedonia with 24 phenotypes were identified, which can be divided into 5 main groups: psychiatric/neurological diseases, inflammatory diseases of the digestive system, respiratory diseases, oncological diseases and metabolic disorders. The most significant causal effects of anhedonia were found for breast cancer (p=0.0004, OR=0.9986, 95% confidence interval (CI) (0.9978-0.999)), minimal depression phenotype (p=0.009, OR=1.004, 95% CI (1.001-1.007)), as well as for apolipoprotein A (p=0.01, OR=0.973, 95% CI (0.952-0.993)) and respiratory diseases (p=0.01, OR=0.9988, 95% CI (0.9980-0.9997)). CONCLUSION: The polygenic nature of anhedonia may cause the risks of comorbidity of this phenotype with a wide range of somatic diseases, as well as may be associated with mood disorders.

[Association of depression and anxiety with somatic diseases: negative lifestyle factors impact]. / Svyaz' depressii i trevogi s somaticheskimi zabolevaniyami: rol' negativnykh vneshnikh faktorov.

OBJECTIVE: To assess the associations of various depression and anxiety phenotypes with manifestations of different somatic disorders and negative lifestyle factors. MATERIAL AND METHODS: The study involved 5116 people. In the online questionnaire, participants provided information about age, sex, height and weight, as well as a history of smoking, alcohol use, physical activity and diagnoses/symptoms of various physical diseases. Self-questions based on the DSM-5 criteria and the online version of the HADS were used to screen for phenotypes of affective and anxiety disorders in a population sample. RESULTS: An association of both subclinical and clinical depressive symptoms on HADS-D was noted for respondents with weight gain (OR 1.43; CI: 1.29-1.58, p<0.05 and OR 1,CI: 1.05-1.52, p<0.05, respectively), increased BMI (OR 1.36; CI: 1.24-1.48, p<0.05 OR 1.27; CI: 1.09-1.47, p<0.05 respectively), and decreased physical activity (OR 1.67; CI: 1.35-2.07, p<0.05 and OR 2.35; CI: 1.59-3.57, p<0.05, respectively) at the time of testing. The phenotypes of depression, anxiety disorders, and bipolar disorder by DSM criteria were associated with a history of smoking. (OR 1.37; CI: 1.18-1.62, p<0.001; OR 1.36; CI: 1.24-1.48, p<0.05 and OR 1.59; CI: 1.26-2.01, p<0.001, respectively). For higher BMI the association was reported only for the bipolar depression phenotype (OR 1.16; CI: 1.04-1.29, p<0.05), and with a decrease in physical activity - for the phenotypes of major depression and anxiety disorders (OR 1.27; CI: 1.07-1.52, p<0.05 and OR 1.61; CI: 1.31-1.99, p<0.001, respectively). A significant association with various somatic disorders was noted for all phenotype variants, but to the greatest extent for those based on DSM criteria. CONCLUSIONS: The study confirmed the association of negative external factors and various somatic disorders with depression. These associations were noted for various phenotypes of anxiety and depression, both in severity and structure, and may be due to complex mechanisms that have shared biological and environmental mechanisms.

[Validation of a DSM-5-based screening test using digital phenotyping in the Russian population]. / Validatsiya skriningovogo testa, osnovannogo na kriteriyakh DSM-5, metodom tsifrovogo fenotipirovaniya na rossiiskoi populyatsii.

OBJECTIVE: To evaluate the validity of a depression and anxiety screening test based on DSM-5 diagnostic criteria to identify cases of these conditions simultaneously assessed with the validated Hospital Anxiety and Depression Scale (HADS) in a population sample by digital phenotyping. MATERIAL AND METHODS: This cross-validation study included 5.116 respondents (mean age 36.9 (9.8)), of which 49.4% (2526) were women. The depression and anxiety screening test was done in electronic form and based on the DSM-5 diagnostic criteria for major depressive disorder and generalized anxiety disorder. The validated HADS scale was used as a standard test. The categories of depression (HADS-D) and anxiety (HADS-A) phenotypes were formed with a cutoff of ≥8 points and ≥11 points. The main parameters of the validity of the screening test were calculated, including accuracy (Ac), sensitivity (Sn) and specificity (Sp) with their 95% confidence intervals [CI]. RESULTS: The prevalence of current depression and anxiety according to the screening test was 7.8% (400) and 12.5% (639), respectively. The prevalence of lifetime depression was 25.9% (1327). For the HADS-D depression subscale with cut-offs of ≥11 and ≥8 points, the prevalence of depression was 3.4% (174) and 15% (766), respectively. For the HADS-A anxiety subscale with cut-offs of ≥11 and ≥8 points, the prevalence of anxiety was 8.9% (456) and 31.8% (1628), respectively. For HADS-D and HADS-A with a cutoff of ≥11 points, the parameters of current depression were Ac=92%, Sn=47% (CI 95% [39-54]), Sp=94% (CI 95% [93-94]), lifetime depression - Ac=75%, Sn=63% (CI 95% [56-70]), Sp=75% (CI 95% [74-77]) and current anxiety - Ac=88%, Sn=54% (CI 95% [50-59]) and Sp=92% (CI 95% [90-92]). For HADS-D and HADS-A with a cutoff of ≥8 points, the parameters of current depression were Ac=86%, Sn=30% (CI 95% [27-33]), Sp=96% (CI 95% [95-97]), lifetime depression - Ac=74%, Sn=51% (CI 95% [48-55]), Sp=75% 79% (CI 95% [77-80]) and current anxiety - Ac=75%, Sn=31% (CI 95% [29-33]), Sp=96% (95% CI [95-97]). CONCLUSION: The high Ac and Sp of this test allows it to be used for screening purposes to identify (but not exclude) cases of depression and anxiety in the population. However, further studies are needed to validate the screening test using a diagnostic interview with a physician.

[Family history of mood disorders may weaken the link between adverse childhood experience and suicidality in patients with depression]. / Svyaz' semeinoi otyagoshchennosti rasstroistvami nastroeniya s neblagopriyatnym detskim opytom i suitsidal'nost'yu u patsientov s depressiei.

OBJECTIVE: To study the impact of family history of mood disorders (FHMD), comprising genetic factors associated with depression, on the association between adverse childhood experience (ACE) and suicidality in depression. MATERIAL AND METHODS: This multicenter cross-sectional study included 200 in- and outpatients (64% (n=128) women, mean age - (M (SD)) 36.21 (15.09) yrs.) with depression. Self-reports about FHMD and lifetime suicide attempts were obtained in clinical interview. The lifetime intensity of suicidal ideas and behavior was assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS), ACE - by the Adverse Childhood Experience International Questionnaire (ACE-IQ). RESULTS: FHMD did not affect the prevalence of ACE, suicide attempts and C-SSRS scores. We found that FHMD weakens the link between ACE and the risk of suicide attempt. The emotional neglect itself increased the risk of suicide attempt (p=0.001, OR=4.428, CI 95% [1.797-10.911]), but reduced it in patients with FHMD (p=0.03, OR=0.128, CI 95% [0.018-0.893]). GLM analysis revealed that FHMD significantly affected the association between suicidal ideas and domestic violence (p=0.045) and between suicidal behavior and emotional neglect (p=0.015) and abuse (p=0.044). CONCLUSION: FHMD may weaken the link between ACE and suicidality in patients with depression. Suicidality in these patients may be underlined by mechanisms not involved in the response to ACE although more studies are needed.

[Contemporary GWAS studies of depression: the critical role of phenotyping]. / Sovremennye issledovaniya po polnogenomnomu poisku assotsiatsii pri depressii: kriticheskaya rol' fenotipirovaniya.

The need to use large samples to identify the genetic risk loci of mental disorders has led us to the dilemma of phenotyping quality. Especially this problem relates to such common mental disorders as depression (lifetime prevalence 16.2%). On the one hand, there is a very resource-intensive method of capturing patient data by physicians using diagnostic criteria of mental disorders (DSM-V/ICD-10). On the other, there is a popular method of minimal phenotyping using hospital registers, self-reports of respondents on symptoms, diagnosis and treatment of depression. To date, there is no ideal method for phenotyping depression because all of them focus only on its clinical symptoms. The active usage of minimal phenotyping in Genome-Wide Association Study (GWAS) has led to a significant increase in both clinical and genetic heterogeneity of depression. However, an important limitation of using DSM-V/ICD-10 is the high cost of phenotyping due to the involvement of medical specialists. Thus, the most rational is to use electronic diagnostic questionnaires based on DSM-V/ICD-10 criteria. Such an approach will accelerate the increase in research capacity, but will preserve all internal contradictions inherent in official diagnostic classifications (heterogeneity of phenotypes, absence of objective diagnostic criteria, categorical approach, etc.). In this regard, the critical role of psychiatric epidemiology is growing both in the development of standardized tools for operationalized diagnostic criteria and in future GWAS by introducing new phenotypic subtypes of depression and its dimensions.

[An associations of possible genetic risk markers for Internet addiction with childhood trauma experience and personality traits in young adults : preliminary results]. / Svyaz' geneticheskikh markerov riska razvitiya internet-zavisimosti s detskim psikhotravmiruyushchim opytom i lichnostnymi osobennostyami u molodykh vzroslykh: predvaritel'nye rezul'taty.

OBJECTIVE: To study was to test an associations of the preliminary genetic risk markers for Internet addiction (IA) with clinical, psychological and personality characteristics, taking into account the childhood traumatic experience, in 44 IA persons compared with 120 healthy individuals. MATERIAL AND METHODS: The study included 164 participants: 44 individuals with IZ (group IZ), male and female, aged 16 to 30 years in the absence of diagnoses of mental health problems. diseases from rubrics F00-09 and F20-29 (ICD-10) and 120 healthy (control group). RESULTS AND CONCLUSION: We have found an associations of the preliminary IA genetic risk markers with some personality traits and behavioral characteristics (TCI-125, TIPI) and with the childhood trauma experience (ACE IQ, CTQ), both for healthy individuals and to a greater extent for IA individuals, that may suggests the possible effects of the gene-environment interaction on a risk of developing IA. The data obtained on the structure of associations between IA genetic risk markers and individual psychological characteristics under the significant influence of the childhood trauma experience allow us to proceed with the construction of models for IA risk prediction taking into account the "gene - environment" interactions.

[Modern approaches to the genetics of depression: scopes and limitations]. / Sovremennye podkhody k izucheniyu genetiki depressii: vozmozhnosti i ogranicheniya.

Recent findings in candidate genes for depression showed significant replication failures and thus appeared irrelevant. Much of the earlier studies' limitations can be overcome by the strategy of genome-wide association studies (GWAS), which aims to identify associations between different genomic variants and phenotypic traits without pathophysiological hypotheses application. With the use of such studies, it seems possible to calculate polygenic risk scores (PRS) as a promising approach for predicting depression risk. The aim of this review is to analyze modern approaches of genetic research used to assess the risk of depression in a population.

[Family history of affective disorders, the gender factor and clinical characteristics of depression]. / Semeinaya otyagoshchennost' affektivnymi rasstroistvami, gendernyi faktor i klinicheskie kharakteristiki depressii.

OBJECTIVE: Analysis of clinical features of development and course of depression in patients with FH of mood disorders taking into account sex differences. MATERIAL AND METHODS: This multicenter cross-sectional study included patients over 18 years of age with depressive episode/recurrent depressive disorder. Clinical characteristics of depression, presence of comorbid mental illness and family history (FH) information were obtained in a structured clinical interview. RESULTS: One hundred and seventy-one patients (mean age (M (SD)) 40.87 (15.86) y.o.), including 64.5% of women, were enrolled in the study. FH was revealed in 30.2% of patients. The proportion of FH did not differ in men and women (p=0.375). Generalized anxiety disorder (GAD) was more frequent in FH positive patients (p=0.016). Logistic regression also revealed that FH is a risk factor for concomitant GAD (p=0.019, OR=2.4). The GLM demonstrated a significant joint effect of FH and sex on the maximum duration of a depressive episode (p=0.044), as well on the number of suicide attempts (p=0.055) and the number of depressive episodes as a trend (p=0.072). CONCLUSION: We have demonstrated the specific interaction of FH of mood disorders with sex on clinical course of depression. Thus, the manifestation of a genetic influence on the clinical phenotype of depression can be significantly moderated by sex.

[Anhedonia in depression: neurobiological and genetic aspects]. / Angedoniya pri depressii: neirobiologicheskie i geneticheskie aspekty.

Anhedonia is indeed a pathogenetically important clinical phenotype and a promising endophenotype for depressive symptoms with a very high contribution of biological and genetic factors. Neurobiological mechanisms of anhedonia are impaired functioning of the reward system of the brain, which is confirmed by many neuroimaging, genetic and experimental studies. Anhedonia has a trans-diagnoctic character and should be understood as a complex phenomenon, and it is important to correctly evaluate it within the framework of a particular research paradigm. It seems optimal to form several complementary research strategies that evaluate the most important «facets¼ of anhedonia, regardless of the nosological form of the disease, within the framework of one study using various methods to search for adequate biomarkers of anhedonia severity (genetic, neuroimaging, biochemical). Given the high-quality organization of such comprehensive studies based on the correct methodology of evidence-based medicine, it is likely that significant biomarker systems will be available in the near future, which, if replicated in independent samples, can be used to personalize the diagnosis and treatment of depression.

[GWAS-based polygenic risk scores for depression with clinical validation: methods and study design in the Russian population]. / Poligennye shkaly riska razvitiya depressii na osnove GWAS s klinicheskoi validatsiei: metodologiya i dizain issledovaniya v rossiiskoi populyatsii.

Depression is one of the leading causes of decreased quality of life and social functioning of patients. In the context of preventive medicine, the prevention of depression becomes a priority. To achieve the goals of prevention, it is necessary to identify specific population risk groups - individuals with a high genetic risk of depression. The paper describes the project aimed at developing a genetic test system based on polygenic risk scores (PRS) for depression, considering the multi-ethnicity and multicultural diversity of the Russian population. As a result of the study, data on the genetic architecture of depression (GWAS) and PRS for depression will be obtained for the first time. The emergence of a genetic test system developed in the study of the Russian population and in the conditions of a constant decrease in the cost of genetic research will allow an effective transition to preventive medicine in the area of mental health.

[Clinical and psychological features of people with internet dependence: experience of a pilot study]. / Kliniko-psikhopatologicheskie osobennosti lits s internet-zavisimost'yu: opyt pilotnogo issledovaniya.

OBJECTIVE: The prevalence of Internet addiction (IA) is growing steadily, especially among the younger generation. The purpose of this multicenter study was to investigate the socio-demographic characteristics, clinical varieties, and profile of psychopathological symptoms of mental disorders in patients with IA. MATERIAL AND METHODS: The study included 2 groups: the main group consisted of 44 people, aged 16 to 34 years, average age 22.00±0.66 years, 33 (75%) men, 11 (25%) women; the control group included 120 people, aged 19 to 30 years, average age 23.13±0.18 years, 90 (74.3%) men, 30 (26.7%) women. Groups were identified at the testing stage based on the total score on the Chen Internet Addiction Scale (CIAS). The main group included individuals who scored CIAS 65 points or higher. The specially developed Unified Study Card, The Mini international neuropsychiatric interview (MINI), the Hospital Anxiety and Depression Scale (HADS), the Beck Depression Questionnaire (BDI), the Prodromal Questionnaire-16 (PQ-16), the Symptom Checklist-90-Questionnaire Revised (SCL-90-R). RESULTS AND CONCLUSION: There were more people with secondary specialized education and unemployed in the main group. The family burden of addiction and psychiatric disorders did not differ in both groups, and the heredity of somatic diseases was lower in the IA group. In the IA group, a psychiatric diagnosis was made 9 times more often. The severity of affective and anxiety disorders was higher in the IA group, while the risk of psychosis was low that allows considering the symptoms of IA outside the framework of subpsychotic mental disorders. The features of the psychopathological symptoms of IA were: total «tension¼ of the psychopathological profile; a relatively uniform and slightly specific profile of psychopathological symptoms with a certain tendency to the prevalence of personality-related stress manifestations.

[The role of family studies in research of neurobiological basis of depressive disorders]. / Rol' semeinykh issledovanii v izuchenii neirobiologicheskogo bazisa depressivnykh rasstroistv.

Depression belongs to a large class of multifactorial diseases and genetic factors play a significant role in its formation, development and clinical manifestations. The authors present an overview of current studies of recurrent depressive disorder (RDD), a heterogeneous group of disorders with phenotypically similar psychopathological symptoms. A study of families with a high risk for RDD using clinical and biological (including genetic) approaches can greatly help in understanding of the neurobiological basis of depressive disorders, as well as in the identification of endophenotypes of depression. The most important criterion of the endophenotype is its heritability, which can be proved only within the framework of family design research. Comprehensive clinical and molecular genetic studies based on family design have the best prospects.

[Genetic comorbidity of depression and somatic disorders]. / Geneticheskaia determinirovannost' komorbidnosti depressii i somaticheskikh zabolevanii.

The aim of our review was to evaluate the perspectives of new therapeutic approaches in comorbid depressive and somatic disorders based on common pathological mechanisms and their genetic risk factors. Literature analysis showed that depression was a complex heterogeneous condition associated with significant prevalence of metabolic, cardiovascular and immune disturbances. The understanding of common molecular mechanisms of risks and course of abovementioned disorders could provide a new strategy for early diagnosis and therapeutic optimization and give the opportunity of 'targeted' approach to different pathological elements.

[An essential negative effect of a family history of substance use on readiness for drug dependence rehabilitation treatment in inpatients with addictions]. / Negativnoe vliianie semeinoi otiagoshchennosti na gotovnost' statsionarnykh patsientov s narkoticheskoi zavisimost'iu k prokhozhdeniiu reabilitatsionnoi programmy.

AIM: To reveal objective factors predicting the readiness of inpatient drug treatment patients to undergo a rehabilitation program. MATERIAL AND METHODS: In a retrospective comparative study, drug-dependent individuals (n=199, 16.6% females, 83.4% men, 91.5% opioid-dependent) were studied. After conducting motivational activities based on cognitive-behavioral psychotherapy, the premorbid, anamnestic, clinical, socio-demographic characteristics of patients were studied as possible predictors of readiness for rehabilitation using binary logistic regression. RESULTS: Family history of substance use reduced the probability of readiness for rehabilitation by >4,5 times (p<0.0001, Exp (B) = 4.577, CI 95% [2.0556, 10.190]). The influence of other factors was weaker and manifested itself only with their combinations (female sex + use of several psychoactive drugs; intravenous drug injection + polydrug addiction; non-remission course of disease + family history of substance use) which increased the likelihood of readiness for rehabilitation. There was no effect of social/demographic variables. CONCLUSION: Family history of substance use significantly reduces the likelihood of readiness for rehabilitation. The clinical severity of the disease, on the other hand, increases the chances of readiness. Patients with a family history of substance use represent a specific group of patients requiring maximum efforts in the process of motivation for rehabilitation.

The prognostic role of depression as a predictor of chronic somatic diseases manifestation.

The negative impact of depression on the course and outcome of somatic disorders is well-known and has a solid theoretical basis. The analyses of prospective studies confirm the role of depression as an independent and significant risk factor for widespread chronic somatic disorders including such severe and life-threatening conditions as cardiovascular diseases, diabetes and oncological pathology. The majority of somatic disorders and depression are the part of the big class of hereditary diseases with multifactorial character and polygenic nature. It is likely, that the genetic risk diversity of these diseases in population is close. There is also a high probability of genetic risks levels overlap (or of common «cluster¼) of two or more diseases in one individual, with one disorder being major depression. In that case such diseases could be considered «genetically comorbid¼ and manifestation of one disease could alter the risks of other. Precise and informative diagnostic tools could detect subsyndromal depression that could be the prognostic sign of the high risk and rapid manifestation of somatic diseases. Thus, patients with depressive disorder could be considered as a group with high risks of diverse range of somatic pathology. The coalescence of fundamental biomedical scientists and internists (psychiatrists and other physicians) could lead to the elaboration of specific complex preventative measures including social ones.

[Combination of DAT and DBH gene polymorphisms with a family history of alcohol use disorders increases the risk of withdrawal seizures and delirium tremens during alcohol withdrawal in alcohol-dependent men]. / Sochetanie polimorfizma genov DAT i DBH s semeinoi otyagoshchennost'yu po alkogol'noi zavisimosti uvelichivaet risk razvitiya sudorozhnykh pristupov i alkogol'nykh psikhozov u muzhchin.

AIM: To explore the genetic influence of a family history of alcohol use disorders and the dopamine transporter SLC6A3 (DAT1) and dopamine beta-hydroxylase (DBH) gene polymorphisms on the risk of severe complications (withdrawal seizures (AWS) and delirium tremens (DT)) during alcohol withdrawal in alcohol-dependent men. MATERIAL AND METHODS: We investigated the effects of 3 previously reported candidate genetic variations: 40-bp variable number tandem repeat (VNTR) polymorphism and C/T exon 15 (rs27072) in the 3' untranslated region (3' UTR) of the SLC6A3(DAT1) gene, and -1021 C/T (rs1611115) of DBH gene in 266 alcohol-dependent Russian male inpatients in two groups by presence (SC group: AWS, DT, AWS+DT, n=130) or absence (n=136) of severe complications diagnosed by ICD-10 during current alcohol withdrawal. Clinically important information and a family history of alcohol use disorders (FH) were obtained by semi-structured interview. RESULTS: Patients in SC group more often have positive FH (54.6% vs. 33%, p=0.001) and their age at first alcohol use (FAU) was lower (16±3.53y.o vs. 17±1.66 y.o, p=0.001). Logistic regression revealed that FH predicts severe complications in total (р=0.001) and DT (р=0.003), FAU independently predicts severe complications in total (р=0.008), AWS (р=0.04), DT (р=0.032), AWS+DT (р=0.048) and every year of delay alcohol use decreases the risk by 18-30%. The gene polymorphisms interact with FAU to decrease the FAU influence on the risk of AWS (T variant of DAT (rs27072), р=0.04), (AWS+DT) and DT (T variant of DBH (rs1611115), р=0.023 and р=0.06). The T variant of DAT (rs27072) is associated with FAU (p=0.007) and increases the risk of (AWS+DT) (р=0.036), but decreases the risk of AWS (р=0.038) and of DT (р=0.021) too, but only in interaction with positive FH. The 9 repeat variant (9R) of DAT VNTR is associated with AWS (p=0.009), but the risk of AWS (р=0.004) and of SC in total (р=0.001) are elevated only in 9R carriers with positive FH. The 9R independently increases the risk of DT (р=0.048) and the effect become more robust in 9R carriers with high density of FH (р=0.014). The gene x gene interaction decreases the risk of DT (р=0.055). According to an analysis of total cohort of patients, the T variant of DBH (rs1611115) is associated with any kind of manifestation of delirium in alcohol-dependent men (p=0.039). CONCLUSION: This study demonstrate the genetic influence of a family history of alcohol use disorders and DAT and DBH gene polymorphisms on the risk of withdrawal seizures and delirium tremens. The interaction of genetic variations with positive family history provides the most robust effect, the interaction of genetic variations with the age at first alcohol use may «protect¼ their carriers from negative influence of this «behavioral¼ risk factor. Replication in large cohorts of patients is necessary to verify these findings for subsequent use in prevention programs.

[The forecast of illicit drug use in adolescents with addictive behavior: personality traits and the level of genetic risk of substance dependence.] / Prognoz upotrebleniya narkotikov podrostkami s addiktivnym povedeniem: cherty kharaktera i uroven' geneticheskogo riska razvitiya khimicheskoi zavisimosti.

AIM: To clarify the psychological mechanism underlying the genetic risk of substance addiction at the first stage of drug use by adolescents. MATERIAL AND METHODS: Genetic risk was evaluated by genotyping of 5 polymorphisms of the dopaminergic system genes (dopamine receptor D2 and D4 genes and tyrosine hydroxylase gene). Psychological testing was performed using the Russian version of Temperament and Character Inventory (TCI-125). Seventy-five adolescents, aged 14-17 years, (girls 32%), who misused alcohol, including 22 adolescents using drugs, were examined. RESULTS AND CONCLUSION: The level of genetic risk was directly correlated with the probability of drug use by boys, for girls the correlation was not confirmed. The increase of the level of genetic risk for boys was correlated with the increase on the scale «Self-directedness¼ of TCI-125 that may reflect a probable tendency to replacement of negative information, feeling of illusory wellbeing. The findings clarify the direction of measures for the prevention of drug use.

[The 444G/A and -1021 C/T polymorphisms of the dopamine-beta-hydroxylase gene modulate the trajectory of alcohol dependence development].

AIM: To study the influence of 444 G/A (rs 1108580) and -1021 C/T (rs 1611115) polymorphisms of the dopamine beta-hydroxylase (DBH) gene on clinical parameters of the trajectory of alcohol dependence. MATERIAL AND METHODS: Authors studied 548 male inpatients, of Slavic ethnicity, with ICD-10 diagnosis of «alcohol dependence¼ (F-10.2). RESULTS: The effects of DBH * 444 G/A on the rate of formation of alcohol withdrawal syndrome (AWS), and DBH *-1021C/T on the age of onset of alcohol abuse with significant role of the age of first alcohol use were identified. In 444 G/A GG carriers, the development of AWS was accelerated since the beginning of alcohol abuse compared with AA carriers (p=0.026), AG carriers occupied an intermediate position. In 22.5% of GG carriers, AWS developed within 2 years (AA: 8.11%, p=0.005; AG: 17.67%, p=0.04). According to the results of linear regression analysis, in AG carriers the alcohol abuse (p=0.037) and the AWS (p=0.049) developed earlier than in AA carriers if the first alcohol use occured at the age of about 15 years. Among -1021C/T genotype carriers who began to abuse alcohol at an early age (before 20 years), there were 23.45% patients with CC genotype and only 11.97% with a T allele (genotypes CT+TT) (p=0.03), but T carriers began to abuse alcohol earlier than others (p=0.05) if the first alcohol use occurred at the age of about 16 years. CONCLUSION: The results can be used to search for genetic markers for prognosis of alcohol dependence development.