ANALYSIS OF GENDER DIFFERENCES IN SPECTRAL CHARACTERISTICS OF HEART RATE AND QT DISPERSION IN YOUNG ALCOHOL-DEPENDENT PATIENTS

The aim of the paper is to study gender differences in spectral characteristics of heart rate and Q-Tcd dispersion in young alcohol-dependent patients. Materials and Methods. The authors examined 60 patients: 30 men and 30 women, their average age was 36.00 (33.75–40.00) and 37.50 (33.75–41.25) years old, respectively. The control group was composed of healthy individuals: 15 men aged 35.00 (29.00–39.00) years old and 15 women aged 31.00 (28.00–40.00) years old. Evaluation of heart rate variability was carried out on a high-resolution ECG apparatus "Poly-Spectrum 8/EX" (Russia), 5-minute recordings were made with further sampling of spectral heart rate indicators. Q-Tcd and QTc dispersion was assessed using a high-resolution ECG device "Poly-Spectrum 8/EX" (Russia) in 12 standard leads lasting 10 seconds each. Agilent 6850 chromograph (USA) was used to estimate blood ethanol concentration. Results. The data on the frequency and severity of the heterogeneity of ventricular myocardium repolarization indicated that men and women with Q-Tcd >70 ms in acute and withdrawal periods dominated over those with borderline Q-Tcd values. The acute period was characterized by a larger number of males with Q-Tcd dispersion >50 ms if compared with women. During the withdrawal period, the number of patients with pathological Q-Tcd dispersion increased. Moreover, the pathology was more obvious in males. There was also a significant decrease in all spectral characteristics of the heart rate in alcohol-dependent patients in the acute and withdrawal periods against the predominance of the sympathetic component (low-frequency heart rate fluctuations) over the parasympathetic one (high-frequency heart rate fluctuations). Conclusions. Alcohol excess in young patients without overt cardiac pathology is accompanied by a decrease in spectral characteristics of heart rate variability and an increase in the QT dispersion. Alcohol-dependent men have more pronounced abnormalities of the repolarization processes than alcohol-dependent women. Gender analysis of spectral parameters shows an equally directional decrease in parameters in alcohol-dependent men and women in comparison with the control group. Key words: spectral characteristics of heart rate variability, HRV, alcohol dependence, corrected Q-Tcd dispersion, corrected QTc interval, QT interval, Q-Td dispersion. Цель – изучение гендерных особенностей спектральных характеристик кардиоритма и дисперсии интервала Q-Tdc у алкогользависимых пациентов молодого возраста. Материалы и методы. Обследовано 60 пациентов: 30 мужчин и 30 женщин, средний возраст 36,00 (33,75–40,00) и 37,50 (33,75–41,25) года соответственно. Контрольную группу составили здоровые лица: 15 мужчин в возрасте 35,00 (29,00–39,00) года и 15 женщин в возрасте 31,00 (28,00–40,00) года. Оценка вариабельности ритма сердца проводилась на аппарате ЭКГ высокого разрешения «Поли-Спектр 8/ЕХ» (Россия) короткими записями длительностью 5 мин с дальнейшей выборкой спектральных показателей ритма сердца. Оценка дисперсии интервалов Q-Tcd и QTc проводилась на аппарате ЭКГ высокого разрешения «Поли-Спектр 8/ЕХ» (Россия) в 12 стандартных отведениях, длительность записи составила 10 с. Концентрация этанола в крови определялась хромографом Agilent 6850 (США). Результаты. Данные по частоте и выраженности гетерогенности процессов реполяризации миокарда желудочков свидетельствуют о преобладании лиц с продолжительностью Q-Tсd более 70 мс среди мужчин и женщин в острый и абстинентный периоды по сравнению с числом пациентов с пограничными значениями Q-Tсd. Острый период характеризуется большим количеством пациентов с дисперсией Q-Tсd более 50 мс у мужчин по сравнению с женской группой. В абстинентный период число лиц с патологической дисперсией Q-Tсd увеличивается, причем несколько быстрее у лиц мужского пола. Также отмечается значительное снижение всех спектральных характеристик кардиоритма у алкогользависимых пациентов в острый и абстинентный периоды алкогольного воздействия на фоне преобладания симпатической составляющей (низкочастотные колебания сердечного ритма) над парасимпатической (высокочастотные колебания сердечного ритма). Выводы. Алкогольный эксцесс у пациентов молодого возраста без манифестной кардиальной патологии сопровождается снижением спектральных характеристик вариабельности ритма сердца и увеличением дисперсии интервала QT. У алкогользависимых мужчин присутствуют более выраженные нарушения процессов реполяризации, чем у алкогользависимых женщин. Гендерный анализ спектральных параметров показывает равнонаправленное снижение показателей у алкогользависимых мужчин и женщин в сравнении с лицами контрольных групп. Ключевые слова: спектральные характеристики кардиоритма, ВРС, алкогольная зависимость, корригированная дисперсия интервала Q-Tcd, корригированный интервал QTc, интервал QT, дисперсия интервала Q-Td.

Initial Study on COMT and DRD2 Gene Polymorphisms as Well as the Influence of Temperament and Character Trait on the Severity of Alcohol Craving in Alcohol-Dependent Patients

The main aim of this work was to determine the impact of COMT and DRD2 gene polymorphisms together with temperament and character traits on alcohol craving severity alcohol-dependent persons. The sample comprised of 89 men and 16 women (aged 38±7). For the sake of psychological assessment various analytic methods have been applied like the Short Alcohol Dependence Data Questionnaire (SADD), Penn Alcohol Craving Scale (PACS) or Temperament and Character Inventory (TCI) test. The SNP polymorphism of the analyzed genes was determined by Real Time PCR test. The results showed, that the COMT polymorphismmay have an indirected relationship with the intensity and changes in alcohol craving during abstinence. The DRD2 receptor gene polymorphisms are related with the intensity of alcohol craving. It seems that the character traits like “self-targeting”, including “self-acceptance”, are more closely related to the severity of alcohol craving and polymorphic changes in the DRD2 receptor than temperamental traits. Although this is a pilot study the obtained results appeared to be promising and clearly indicate the link betweengene polymorphisms alcohol craving and its severity.

Mental Imagery Skills in Alcohol-Dependent Subjects and Their Associations With Cognitive Performance: An Exploratory Study During Residential Rehabilitation

People in alcohol-detoxification experience deficits in motor and non-motor functions including cognitive performance. Imagery, the cognitive process of generating visual, auditory or kinesthetic experiences in the mind without the presence of external stimuli, has been little studied in Alcohol Use Disorders (AUD). This pilot study aims to observe the cognitive abilities useful for the inspection, maintenance, generation and manipulation of images in these patients during residential rehabilitation and investigate the relationships with their cognitive performance. Thirty-six subjects who completed the 28-day rehabilitation program for alcohol addiction, completed the Mental Imagery Test (MIT) and Neuropsychological Battery (ENB-2). The global score at MIT did not show pathological scores. The 11.1% of AUD patients showed an impaired global score in the cognitive performance and the 5.7% with scoring at limits of norm. Significant correlations were found between Mental Imagery abilities and ENB-2 subscale and stepwise regression analysis showed the close association between the ability of imagery (Mental Imagery Test) and the overall cognitive performance (ENB-2) in alcohol dependent patients and this relationship is stronger than other cognitive tasks.

Combining Metabolomics and Interpretable Machine Learning to Reveal Plasma Metabolic Profiling and Biological Correlates of Alcohol-Dependent Inpatients: What About Tryptophan Metabolism Regulation?

Alcohol dependence (AD) is a condition of alcohol use disorder in which the drinkers frequently develop emotional symptoms associated with a continuous alcohol intake. AD characterized by metabolic disturbances can be quantitatively analyzed by metabolomics to identify the alterations in metabolic pathways. This study aimed to: i) compare the plasma metabolic profiling between healthy and AD-diagnosed individuals to reveal the altered metabolic profiles in AD, and ii) identify potential biological correlates of alcohol-dependent inpatients based on metabolomics and interpretable machine learning. Plasma samples were obtained from healthy (n = 42) and AD-diagnosed individuals (n = 43). The plasma metabolic differences between them were investigated using liquid chromatography-tandem mass spectrometry (AB SCIEX® QTRAP 4500 system) in different electrospray ionization modes with scheduled multiple reaction monitoring scans. In total, 59 and 52 compounds were semi-quantitatively measured in positive and negative ionization modes, respectively. In addition, 39 metabolites were identified as important variables to contribute to the classifications using an orthogonal partial least squares-discriminant analysis (OPLS-DA) (VIP > 1) and also significantly different between healthy and AD-diagnosed individuals using univariate analysis (p-value < 0.05 and false discovery rate < 0.05). Among the identified metabolites, indole-3-carboxylic acid, quinolinic acid, hydroxy-tryptophan, and serotonin were involved in the tryptophan metabolism along the indole, kynurenine, and serotonin pathways. Metabolic pathway analysis revealed significant changes or imbalances in alanine, aspartate, glutamate metabolism, which was possibly the main altered pathway related to AD. Tryptophan metabolism interactively influenced other metabolic pathways, such as nicotinate and nicotinamide metabolism. Furthermore, among the OPLS-DA-identified metabolites, normetanephrine and ascorbic acid were demonstrated as suitable biological correlates of AD inpatients from our model using an interpretable, supervised decision tree classifier algorithm. These findings indicate that the discriminatory metabolic profiles between healthy and AD-diagnosed individuals may benefit researchers in illustrating the underlying molecular mechanisms of AD. This study also highlights the approach of combining metabolomics and interpretable machine learning as a valuable tool to uncover potential biological correlates. Future studies should focus on the global analysis of the possible roles of these differential metabolites and disordered metabolic pathways in the pathophysiology of AD.

Associations of NLRP3 and CARD8 gene polymorphisms with alcohol dependence and commonly related psychiatric disorders: a preliminary study

We investigated two functional polymorphisms in NLRP3 inflammasome genes (NLRP3 rs35829419 and CARD8 rs2043211) and their association with alcohol dependence and related anxiety, depression, obsession-compulsion, or aggression in 88 hospitalised alcohol-dependent patients, 99 abstinent alcohol-dependent participants, and 94 controls, all male Caucasian. Alcohol dependence-related psychiatric disorders were assessed with the Zung Depression and Anxiety scale, Buss-Durkee Hostility Inventory, Alcohol Use Disorders Identification Test, Brief Social Phobia Scale, Obsessive Compulsive Drinking Scale, and Yale-Brown Obsessive-Compulsive Scale. For genotyping we used the allele-specific quantitative polymerase chain reaction-based methods. The three groups differed significantly in CARD8 rs2043211 distribution (P=0.049; chi-squared=9.557; df=4). The NLPR3 rs35829419 polymorphism was not significantly associated with alcohol dependence. In hospitalised alcohol-dependent patients the investigated polymorphisms were not associated with scores indicating alcohol consumption or comorbid symptoms. In abstinent alcohol-dependent subjects homozygotes for the polymorphic CARD8 allele presented with the highest scores on the Zung Anxiety Scale (p=0.048; df=2; F=3.140). Among controls, CARD8 genotype was associated with high scores on the Obsessive Compulsive Drinking Scale (P=0.027; df=2; F=3.744). In conclusion, our results reveal that CARD8 rs2043211 may play some role in susceptibility to alcohol dependence, expression of anxiety symptoms in abstinent alcohol-dependent subjects, and in obsessive compulsive drinking in healthy controls. However, further studies with larger cohorts are required to confirm these preliminary findings.

Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Protracted Alcohol Withdrawal Symptoms in Male Alcohol-Dependent Patients

Protracted alcohol withdrawal symptoms (PAWS), characterized by the presence of substance-specific signs and symptoms (including anxiety, irritability, mood instability, insomnia, and cravings), make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. The goal of this study was to evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on PAWS and plasma brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and leptin levels in patients with alcohol dependency. A total of 114 patients with alcohol dependence were randomly divided into two groups: the treatment group and the control group. The patients in the treatment group were treated with taVNS of the bilateral auricular concha using an ear vagus nerve stimulator. The Pennsylvania Alcohol Craving Scale was used to evaluate the extent of craving for alcohol. The Self-Rating Anxiety Scale and Self-Rating Depression Scale (SDS) were used to evaluate the extent of anxiety and depression symptoms, respectively. The Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality. Enzyme-linked immunosorbent assay was used to measure plasma BDNF, IL-6, TNF-α, and leptin levels. The results showed that the SDS and PSQI scores were significantly lower in the treatment group than in the control group. Moreover, compared with the control group, the average BDNF levels in the treatment group were significantly increased. These results suggest that taVNS could improve the depression symptoms and sleep quality in alcohol-dependent patients after withdrawal, which might be related to the upregulation of plasma BDNF levels.