scholarly journals Genetic features of the dopaminergic neurotransmitter system in patients with alcohol dependence and depression comorbidity

Author(s):  
A. E. Nikolishin ◽  
V. M. Brodyansky ◽  
N. A. Chuprova ◽  
A. V. Solovieva ◽  
A. O Kibitov

Aim. Test the hypothesis about the effect of polymorphisms of the DA system on the risk of developing depression in patients with alcohol dependence. Material and methods. 104 patients: 64 patients with a combination of diagnoses of “alcohol dependence” and “depression” (F10.2 and F32, F33 according to ICD-10, average age 41.23 ± 9.903 years) and 40 patients with a diagnosis of alcohol dependence (F10 .2 according to ICD-10, average age 45.57 ± 10.853 years) and 113 control (average age 43.65 ± 4.318 years). Results. In patients with a combination of AD and depression, the frequency of occurrence of the C allele C polymorphism rs1611115 of the DBH gene is higher than in the control group (p = 0.087, trend). In patients with a combination of AD and depression, the frequency of occurrence of the A allele of the rs1108580 polymorphism of the DBH gene is higher than in patients with AD (p = 0.059, trend). In patients with AD allele A, the DBH gene rs1108580 polymorphism increases the risk of depression by 174.0% (p = 0.009), the DBH gene rs1108580 AA polymorphism increases the risk of depression by 684.1% (p = 0.010), the rs1108580 gene AG polymorphism rs1108580 in the gene DBH increases the risk of depression by 261.1% (p = 0.010). Conclusion. It has been shown for the first time that polymorphic variants of the rs1108580 locus of the DBH gene act as important risk factors for depression in patients with AD. Polymorphism rs1611115 of the DBH gene can also play an important role in the development of depression in patients with AD, which requires further study.

Rheumatology ◽  
2020 ◽  
Author(s):  
Nikolaos Koletsos ◽  
Eugenia Gkaliagkousi ◽  
Antonios Lazaridis ◽  
Areti Triantafyllou ◽  
Panagiota Anyfanti ◽  
...  

Abstract Objectives Patients with SLE have increased cardiovascular mortality. Alterations in both macro- and micro-circulation have been associated with cardiovascular disease. We sought to assess skin microvascular function by using laser speckle contrast analysis (LASCA) in patients with SLE, with and without cardiovascular disease and risk factors. Methods Continuous blood flow was recorded using a LASCA device during baseline, a 5-min arterial occlusion and a 5-min reperfusion period. Results Thirty-five patients with SLE (85.7% women) with a median disease duration 12.0 (6.5–17.5) years and a mean age of 46.3 (8.6) years and 31 controls matched for age, sex and BMI were enrolled. During reperfusion, SLE patients exhibited a smaller peak magnitude compared with controls (161.0 (47.1) vs 197.2 (41.4)%, respectively, P =0.002). Results remained unchanged among 24 SLE patients without cardiovascular disease compared with the control group (169.2 (48.1) vs 195.6 (34.0)%, respectively, P =0.002). Conclusion Our study shows, for the first time, that patients with SLE, even without overt cardiovascular disease or risk factors, exhibit a blunted microvascular reactivity during reperfusion compared with controls. These results show that skin microvascular dysfunction is present in SLE independently of the CV burden that these patients bear and may represent an early sign of vascular damage.


2016 ◽  
Vol 45 (1) ◽  
pp. 50-58 ◽  
Author(s):  
Marie Askenberger ◽  
Per-Mats Janarv ◽  
Throstur Finnbogason ◽  
Elizabeth A. Arendt

Background: The incidence of primary lateral patellar dislocation (LPD) in children aged 9 to 14 years is 0.6 to 1.2 per 1000. Causation is assumed to be multifactorial, including anatomic variants of the patellofemoral (PF) joint that result in a higher risk of LPD. No publication has compared the morphology of the PF joint and anatomic patellar instability risk factors (APIFs) in a primary LPD population versus controls, defining children by skeletal maturity. Purpose: To characterize the PF morphology and APIFs (trochlear dysplasia, abnormal lateral patellar tilt, elevated tibial tubercle–trochlear groove [TT-TG] distance, patella alta) through magnetic resonance imaging (MRI) measurements in skeletally immature children with and without a primary LPD and to identify (potential) distinctive differences between these 2 groups. Study Design: Cross-sectional study; Level of evidence, 3. Methods: A prospective series of 103 skeletally immature children aged 9 to 14 years with an MRI-confirmed primary LPD were matched with a control group of 69 children. The PF morphology and APIFs were assessed during a 2.5-year period with standardized MRI using sagittal and axial views. Results: In the LPD group, 79% had 2 to 4 APIFs compared with 7% in the control group. All major measurements of trochlear dysplasia were significantly different between the 2 groups. The mean central condylar height was significantly higher in the LPD group compared with the control group, resulting in a lower trochlear depth (2.3 vs 4.5 mm, respectively) and higher sulcus angle (156.7° vs 141.1°, respectively). The LPD group had significantly higher values of patellar height, Caton-Deschamps index (1.33 vs 1.15, respectively), lateral patellar tilt (21.1° vs 8.5°, respectively), and TT-TG distance (13.9 vs 9.8 mm, respectively) compared with the control group. The main divergent APIF was trochlear dysplasia (defined as trochlear depth <3 mm), seen in 74% of the LPD group compared with 4% of the control group. Elevated TT-TG distance as a single APIF was never present in the LPD group; patellar tilt was only seen in the LPD group. The most common APIF in the control group was patella alta (36%). Conclusion: There was a significant difference in mean values of all established APIFs between the children with a first-time LPD and the controls. Trochlear dysplasia was the main APIF, and together with lateral patellar tilt (≥20°), they had the strongest association with LPD.


Author(s):  
Т.М. Рожнова ◽  
В.А. Спицын ◽  
С.В. Макаров ◽  
С.В. Костюк

Аддиктивные расстройства относятся к мультифакториальным заболеваниям с клинической, генетической и нейрофизиологической гетерогенностью и высокой коморбидностью с другими расстройствами психического спектра. Определяющее влияние на фенотипическую дисперсию расстройств поведения зависимого характера принадлежит генотипу. Полиморфные варианты генов нейромедиаторных систем головного мозга, кодирующих белки, участвующие в регуляции эффекторных реакций и метаболизме психоактивных веществ (ПАВ), можно рассматривать как маркёры поведенческих паттернов и индивидуальной предрасположенности к зависимому поведению. Цель исследования - анализ полиморфных вариантов генов DRD2/ANKK1 и SLC6A3 дофаминергической системы головного мозга у больных алкоголизмом. Генотипирование по TaqIA-полиморфизму в локусе ANKK1/DRD2 (rs1800497) и VNTR-полиморфизму в гене SLC6A3 (DAT1) проводили с использованием метода ПЦР. Выявлено статистически достоверное преобладание частоты аллеля ANKK1*A1 и генотипа ANKK1*A1A2 в группе мужчин с наличием аддиктивного расстройства в форме алкогольной зависимости по сравнению с фенотипически здоровыми представителями контрольной группы (p<0,001). Частота аллеля *А2 и генотипа *A2A2 в исследуемой группе статически значимо ниже этого показателя контрольной выборки. Аллель ANKK1*A1 является фактором риска развития алкогольной зависимости (RR=4,69; EF=0,15) с теснотой связи средней степени (j=0,21), а ANKK1*A2 обладает протекторным свойством (RR=0,84; PF=0,79). Полученные данные указывают на возможность использования генотипирования генов дофаминэргической системы головного мозга для оценки индивидуальной предрасположенности к алкогольной зависимости - у носителей *A1 гена DRD2/ANKK1 риск формирования зависимости в 4,69 раза выше гомозигот по варианту *А2. Addictive disorders are multifactorial diseases with clinical, genetic and neurophysiological heterogeneity and high comorbidity with other disorders of the mental spectrum. The decisive influence on the phenotypic dispersion of disorders of behavior of a dependent nature belongs to the genotype. Polymorphic variants of genes of the neurotransmitter systems of the brain that encode proteins involved in the regulation of effector reactions and the metabolism of psychoactive substances can be considered as markers of behavioral patterns and an individual predisposition to dependent behavior. Genotyping by TaqIA polymorphism at the ANKK1/DRD2 locus (rs1800497) and VNTR polymorphism in the SLC6A3 gene (DAT1) was performed using the PCR. A statistically significant predominance of the frequency of the ANKK1*A1 allele and the ANKK1*A1A2 genotype was revealed in the group of men with the presence of addictive disorder in the form of alcohol dependence compared to phenotypically healthy representatives of the control group (p <0.001). The frequency of *A2 and genotype *A2A2 were statistically significantly lower in the study group than in the control. The ANKK1*A1 allele is a risk factor for the development of alcohol dependence (RR=4.69; EF=0.15) with a moderate linkage (j=0.21), and ANKK1*A2 has a protective property (RR=0.84; PF=0.79). The data obtained indicate the possibility of using genotyping of the genes of the dopaminergic system of the brain to assess an individual predisposition to alcohol dependence - in carriers of *A1 of the DRD2/ANKK1 gene, the risk of dependence formation is 4.69 higher than homozygotes in the *A2 variant.


2009 ◽  
Vol 7 (4) ◽  
pp. 23-33 ◽  
Author(s):  
Nikolay V Litvjakov ◽  
Maksim B Freydin ◽  
Ravil M Takhauov ◽  
Alena M Ageeva ◽  
Natalia M Volkova ◽  
...  

The association of 13 biallelic polymorphisms of genes hOGG1 977C > G, XPD1 2251A > C, XPG1 3310G > C, XRCC1:580C> T, 839G >A, 1196G>A GSTT1 («+»/«-»), GSTM1 («+»/«-»), CYP2C19 681G> A, NOS3: -665C>T, 774С> T, 894G > T, VNTRint4 with risk of development of malignant new growths (MNG) in conditions of "low-dose" ionizing irradiation was investigated. In 1 group of irradiated patients of malignant new growths there are 96 persons, in 2 group of non-irradiated patients of MNG - 135 persons, in 3 control group - 148 healthy irradiated workers of the Siberian Group of Chemical Enterprises. By means of procedure FDR it is shown that only polymorphic variants of gene CYP2C19681G* are authentically associated with risk of occurrence of MNG against an irradiation. 1 genotype consisting of a combination of 5 polymorphic loci is selected. Frequency of occurrence of this genotype in 1 group makes 16,9 % (14/83), in 2 group - 1,0 % (1/100), in 3 group - 0,84 % (1/119). At its carriers in conditions of low-dose irradiation more than in 20 times the risk of occurrence of MNG (OR between 1 and 3 groups (95 % CI) = 24,14 (3,21-502,64) increases; p = 0,0000581, taking into account the correction of Bonferroni р = 0,01046).


Author(s):  
E. V. Mikhalitskaya ◽  
O. V. Roshchina ◽  
S. A. Ivanova ◽  
N. A. Bokhan

One of the common pathogenetic mechanisms of the formation of alcohol dependence and depressive disorders can be a violation of the neurotransmitter systems, in particular — dopamine. Phosphatidylinositol-4-phosphate-5-kinase type 2 alpha (PIP5K2A) plays an important role in the regulation of neuronal excitability and synaptic dopamine neurotransmission. The aim of this study was to assess the presence of associations of the PIP5K2A gene polymorphic variants with the comorbid course of alcohol dependence and depressive disorders. This study showed differences in the frequency of the genotype distribution of 3 PIP5K2A gene polymorphisms (rs946961, rs1132816, and rs1417374) both between patient groups compared with the control group, and between the patient group and the group with the comorbid course of disorders.


2017 ◽  
Vol 24 (1) ◽  
pp. 2017112
Author(s):  
Serge Ivanovich Ivashchuk ◽  
Larysa Petrivna Sydorchuk

The comorbidities affect the course of pancreatitis significantly; however, this effect has not been evaluated from the perspective of genetic component.The objective of the research was to analyse concomitant chronic diseases as potential risk factors for edematous pancreatitis considering genetic predictors.Materials and methods. The epidemiological analysis of comorbidities (cholelithiasis, urolithiasis, ischemic heart disease, past viral infection) as risk factors for edematous pancreatitis was performed. Polymorphic variants of the IL-4 (rs 2243250) gene being identified in 123 patients and 40 healthy individuals were also involved.Results. In patients with edematous pancreatitis, urolithiasis was observed more frequently than in the control group - by 37.30% (χ2=18.62, p<0.001). The presence of cholelithiasis insignificantly increases the risk of edematous pancreatitis in the future (RR-1.156; 95% CI: 0.972-1.374). The presence of urolithiasis increased the risk of edematous pancreatitis twofold (RR-2.039; 95% CI: 1.346-3.090; p<0.05).Conclusions. 1. Cholelithiasis increases the probability of developing edematous pancreatitis in carriers of the mutant T-allele of the IL-4 gene by 3.7 times (RR=3.69; OR=10.13; 95% CI OR: 3.17-32.42; p<0.05). 2. In the C-allele carriers of the IL-4 (C-590T) gene, the risk of developing acute pancreatitis is twice higher in the presence of urolithiasis or ischemic heart disease, and almost five times higher in case of past viral infection (p<0.05).


Author(s):  
Л.А. Ветрилэ ◽  
Т.И. Невидимова ◽  
Т.В. Давыдова ◽  
И.А. Захарова ◽  
Д.Н. Савочкина ◽  
...  

Целью настоящего исследования было изучение нейроиммунологических особенностей развития алкогольной зависимости, сопровождающейся депрессивными расстройствами, у женщин. В связи с этим был проведён сравнительный анализ содержания в сыворотке крови провоспалительных и противовоспалительных цитокинов и кортизола, как показателя уровня стресса, у женщин с алкогольной зависимостью, с депрессивными расстройствами, а также при их сочетании. Методы. Клиническое обследование, формирование групп для исследования и создание банка биологического материала выполнены на базе отделений аффективных расстройств и аддиктивных состояний и лаборатории клинической психонейроиммунологии и нейробиологии НИИ психического здоровья ФГБНУ «Томского НИМЦ РАН». Клиническая верификация диагноза выполнена психиатрами и наркологами в соответствии с Международной классификацией болезней 10-го пересмотра (МКБ-10). Были исследованы сыворотки крови 58 женщин в возрасте 40-55 лет с установленным диагнозом по МКБ-10: депрессивный эпизод - 16, дистимия - 9, рекуррентное депрессивное расстройство - 10, алкогольная зависимость - 15, зависимость от алкоголя в сочетании с депрессией - 8. Контрольную группу условно здоровых людей, сопоставимую по полу и возрасту, составили 31 женщина, проходивших ежегодную диспансеризацию. Определяли содержание ИЛ-1b, ИЛ-6, ФНО-α, ИЛ-10 и кортизола в сыворотках крови иммуноферментным методом с использованием тест-систем производства «ООО Цитокин» (Санкт-Петербург) и фирмы DBC Diagnostics Biochem Canada Inc, соответственно. Результаты. У женщин с зависимостью от алкоголя наблюдали значимое увеличение провоспалительных (ИЛ-6 и ФНО-α) цитокинов по сравнению с контролем в 2,3 и 1,6 раза, соответственно. Сочетание алкогольной зависимости с депрессией сопровождалось более существенным увеличением содержания ИЛ-1β и ИЛ-6 при сравнении как с контролем, так и с группой женщин с зависимостью от алкоголя без соматической патологии. В сыворотках крови женщин всех обследованных групп по сравнению с контрольной группой условно здоровых женщин было выявлено повышенное содержание кортизола, что свидетельствует о нарушении функции гипоталамо-гипофизарно-надпочечниковой системы при алкогольной зависимости, депрессивных расстройствах, а также о наличии стрессогенных факторов (отмена алкоголя, госпитализация). Заключение. Сочетание алкогольной зависимости и депрессивных расстройств является взаимным отягчающим обстоятельством и неблагоприятным признаком развития как алкогольной зависимости, так и депрессии. Высокое содержание ИЛ-6 может рассматриваться в качестве возможного нейроиммунного биомаркёра сочетанного течения алкогольной зависимости и депрессии, а также может быть использовано в персонализированной профилактике и лечении этой патологии. The aim of this study was to determine neuroimmunological characteristics of the development of alcohol dependence accompanied by depressive disorders in women. For this purpose, serum concentrations of proinflammatory and anti-inflammatory cytokines and cortisol as an indicator of stress intensity were compared in women with alcohol dependence, depressive disorders, and their combination. Methods. Patients underwent a clinical examination, study groups were formed, and a bank of biological material was created at the Department of Affective Disorders, the Department of Addictive States, and the Laboratory of Clinical Psychoneuroimmunology and Neurobiology of the Research Institute of Mental Health of the Tomsk Scientific Research Center. The diagnosis was clinically verified by psychiatrists and narcologists in accordance with the International Classification of Diseases, 10th Revision (ICD-10). Blood serum tests were performed for 58 women aged 40-55 years with the following ICD-10 diagnoses: a depressive episode (n=16), dysthymia (n=9), recurrent depressive disorder (n=10), alcohol dependence (n=15), and alcohol dependence in combination with depression (n=8). The control group of sex- and age-matched without apparent disease healthy people consisted of 31 women who were undergoing a routine annual medical examination. Concentrations of IL-1b, IL-6, TNF-α, IL-10, and cortisol were measured by the enzyme immunoassay with test systems manufactured by Cytokine LLC (St. Petersburg) and DBC Diagnostics Biochem Canada Inc, respectively. Results. In women with alcohol dependence, proinflammatory cytokines (IL-6 and TNF-α) were increased 2.3 and 1.6 times, respectively, compared to the control. The combination of alcohol dependence with depression was associated with a more pronounced increase in IL-1β and IL-6 compared to the control and the group of women with alcohol dependence without somatic pathology. In all examined groups, serum cortisol was higher than in the control group of women without apparent disease, which indicated dysfunction of the hypothalamic-pituitary-adrenal axis in alcohol dependence, depressive disorders, and in presence of stress factors (alcohol withdrawal, hospitalization). Conclusion. Alcohol dependence and depressive disorders are mutually aggravating conditions, and their combination is an unfavorable prognostic sign for both of them. A high concentration of IL-6 can be considered as a possible neuroimmune biomarker for the combination of alcohol dependence and depression and can also be used in personalized prevention and treatment of this pathology.


Crisis ◽  
2016 ◽  
Vol 37 (2) ◽  
pp. 130-139 ◽  
Author(s):  
Danica W. Y. Liu ◽  
A. Kate Fairweather-Schmidt ◽  
Richard Burns ◽  
Rachel M. Roberts ◽  
Kaarin J. Anstey

Abstract. Background: Little is known about the role of resilience in the likelihood of suicidal ideation (SI) over time. Aims: We examined the association between resilience and SI in a young-adult cohort over 4 years. Our objectives were to determine whether resilience was associated with SI at follow-up or, conversely, whether SI was associated with lowered resilience at follow-up. Method: Participants were selected from the Personality and Total Health (PATH) Through Life Project from Canberra and Queanbeyan, Australia, aged 28–32 years at the first time point and 32–36 at the second. Multinomial, linear, and binary regression analyses explored the association between resilience and SI over two time points. Models were adjusted for suicidality risk factors. Results: While unadjusted analyses identified associations between resilience and SI, these effects were fully explained by the inclusion of other suicidality risk factors. Conclusion: Despite strong cross-sectional associations, resilience and SI appear to be unrelated in a longitudinal context, once risk/resilience factors are controlled for. As independent indicators of psychological well-being, suicidality and resilience are essential if current status is to be captured. However, the addition of other factors (e.g., support, mastery) makes this association tenuous. Consequently, resilience per se may not be protective of SI.


2016 ◽  
Vol 37 (4) ◽  
pp. 213-222 ◽  
Author(s):  
Hansjörg Znoj ◽  
Sandra Abegglen ◽  
Ulrike Buchkremer ◽  
Michael Linden

Abstract. There is a growing interest in embitterment as psychological concept. However, little systematic research has been conducted to characterize this emotional reaction. Still, there is an ongoing debate about the distinctiveness of embitterment and its dimensions. Additionally, a categorical and a dimensional perspective on embitterment have been developed independently over the last decade. The present study investigates the dimensions of embitterment by bringing these two different approaches together, for the first time. The Bern Embitterment Inventory (BEI) was given to 49 patients diagnosed with “Posttraumatic Embitterment Disorder (PTED)” and a matched control group of 49 patients with psychological disorders with other dominant emotional dysregulations. The ability to discriminate between the two groups was assessed by t-tests and Receiver Operating Characteristic Curves (ROC curve analysis). PTED patients scored significantly higher on the BEI than the patients of the control group. ROC analyses indicated diagnostic accuracy of the inventory. Further, we conducted Confirmatory Factor Analyses (CFA) to examine the different dimensions of embitterment and their relations. As a result, we found four characteristic dimensions of embitterment, namely disappointment, lack of acknowledge, pessimism, and misanthropy. In general, our findings showed a common understanding of embitterment as a unique but multidimensional emotional reaction to distressful life-events.


2020 ◽  
Vol 29 (2) ◽  
pp. 175-179
Author(s):  
Melania Macarie ◽  
Simona Bataga ◽  
Simona Mocan ◽  
Monica Pantea ◽  
Razvan Opaschi ◽  
...  

Background and Aims: The importance of sessile serrated lesions (SSLs) in the pathogenesis of colorectal carcinoma has been recently established. These are supposed to cause the so-called “interval cancer”, having a rapidly progressive growth and being difficult to detect and to obtain an endoscopic complete resection. We aimed to establish the most important metabolic risk factors for sessile serrated lesions. Methods: We performed a retrospective case-control study, on a series of 2918 consecutive patients who underwent colonoscopy in Gastroenterology and Endoscopy Unit, County Clinical Emergency Hospital, Târgu-Mureș, Romania between 1 st of January 2015-31 th of December 2017. In order to evaluate the metabolic risk factors for polyps’ development, enrolled participants were stratified in two groups, a study group, 33 patients with SSLs lesions, and a control group, 138 patients with adenomatous polyps, selected by systematic sampling for age and anatomical site. Independent variables investigated were: gender, smoking, alcohol consumption, obesity, arterial hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, nonalcoholic liver disease. Results: For SSLs the most common encountered localization was the right colon in 30.55% of cases. By comparative bivariate analysis between SSLs group and control group, it was observed that hypertension (p=0.03, OR 2.33, 95 %CI 1.03-5.24), obesity (p=0.03, OR 2.61, 95 %CI 1.08-6.30), hyperuricemia (p=0.04, OR 2.72, 95 %CI 1.28-7.55), high cholesterol (p=0.002, OR 3.42; 95 %CI 1.48-7.87), and high triglycerides level (p=0.0006, OR 5.75; 95 %CI 1.92-17.2) were statistically associated with SSLs development. By multivariate analysis hypertension and hypertriglyceridemia retained statistical significance. Conclusions: Our study showed that the highest prevalence of SSLs was in the right colon and hypertension and increased triglycerides levels were associated with the risk of SSLs development. These risk factors are easy to detect in clinical practice and may help identifying groups with high risk for colorectal cancer, where screening is recommended.


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