Alcohol use disorder (AUD) is a highly prevalent, comorbid, and disabling disorder. The underlying mechanism of ethanol neurotoxicity and the involvement of oxidative stress is still not fully ...elucidated. However, ethanol metabolism has been associated with increased oxidative stress through alcohol dehydrogenase, the microsomal ethanol oxidation system, and catalase metabolic pathways. We searched the PubMed and genome-wide association studies (GWAS) catalog databases to review the literature systematically and summarized the findings focusing on AUD and alcohol abstinence in relation to oxidative stress. In addition, we reviewed the ClinicalTrials.gov resource of the US National Library of Medicine to identify all ongoing and completed clinical trials that include therapeutic interventions based on antioxidants. The retrieved clinical and preclinical studies show that oxidative stress impacts AUD through genetics, alcohol metabolism, inflammation, and neurodegeneration.
•TPH2 tag SNPs and haplotypes were investigated in alcohol dependence.•TPH2 genetic variability may play a role in alcohol dependence through haplotypes.•TPH2 genetic variability may be associated ...with alcohol-related comorbid symptoms.
Heritability plays an important role in the development and expression of alcohol dependence. The present genetic association study explored the role of TPH2 polymorphisms and their haplotypes to investigate its role in alcohol dependence and comorbid psychopathological symptoms. The sample included 101 subjects currently diagnosed as alcohol abusers, 100 abstinent alcohol-dependent subjects and 97 healthy controls. Subjects were genotyped for TPH2 rs4570625, rs1843809, rs7305115, rs4290270. TPH2 genotypes were not associated with alcohol dependence, but GGAA haplotype was less common (p=0.038) and GTAA and GGGT were more common (p=0.011 and p=0.021, respectively), in currently dependent patients compared to controls. Exploratory analysis of genotypes in currently dependent patients showed that rs1843809 was associated with depressive and aggressive traits (p=0.045 and p=0.001, respectively), rs4290270 with depressive and anxiety traits (p=0.040 and p=0.025, respectively) and rs4570625 with aggressive traits (p=0.011). In abstinent subjects rs1843809 genotype was associated with traits of social anxiety (p=0.003). Only association between rs1843809 and the BDHI score (p=0.001) and associations between GTAA haplotype and Zung Anxiety Scale and BDHI score (p=0.001 and p<0.001, respectively), in currently dependent patients remained significant after applying the Bonferroni’s correction.
Our findings support a potential role of TPH2 in alcohol dependence. TPH2 genetic variability may be also associated with anxiety and aggression traits in alcohol dependent subjects.
Oxidative stress and neuroinflammation are involved in the pathogenesis of alcohol addiction. However, little is known regarding the effect of genetic, behavioral, psychological, and environmental ...sources of origin on the inflammation and oxidative stress pathways of patients with alcohol addiction. Our study aimed to evaluate the impact of selected common functional single-nucleotide polymorphisms in inflammation and oxidative stress genes on alcohol addiction, and common comorbid psychosymptomatology. Our study included 89 hospitalized alcohol-addicted patients and 93 healthy individuals, all Slovenian males. Their DNA was isolated from peripheral blood and patients were genotyped for
rs705379, rs705381, rs854560, and rs662,
rs4880,
rs1050450,
rs1143623, rs16944, and rs1071676,
rs1800795,
rs2228145, and miR146a rs2910164. Kruskal-Wallis and Mann-Whitney tests were used for the additive and dominant genetic models, respectively. Our findings suggested the involvement of
rs1800795 in alcohol addiction. Moreover, our data indicated that the genetic variability of
and
, as well as
and
may be related to comorbid psychosymptomatology, revealing a potential indirect means of association of both the oxidative stress and inflammation pathways.
We investigated two functional polymorphisms in NLRP3 inflammasome genes (
rs35829419 and
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
rs2043211 distribution (P=0.049; chi-squared=9.557; df=4). The
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
allele presented with the highest scores on the Zung Anxiety Scale (p=0.048; df=2; F=3.140). Among controls,
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
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.
Alcohol dependence is a chronic mental disorder that leads to decreased quality of life for patients and their relatives and presents a considerable burden to society. Incretin hormones, such as ...glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are endogenous gut-brain peptides, which can travel across the blood-brain barrier and access the nervous system. Their respective receptors, GIPR and GLP-1R, are expressed in the reward-related brain areas and are involved in memory formation and neurogenesis, which results in behavioral changes in rodent models. The current study investigated the potential association of genetic variability of incretin receptors with alcohol dependence and alcohol-related psychosymptomatology. Alcohol dependence and comorbid psychosymptomatology were assessed in a cohort of Slovenian male participants, comprised of 89 hospitalized alcohol-dependent patients, 98 abstinent alcohol-dependent patients, and 93 healthy blood donors. All participants were genotyped for
GIPR
rs1800437 and
GLP1R
rs10305420 and rs6923761 polymorphisms. For the statistical analysis Kruskal–Wall and Mann–Whitney tests were used in additive and dominant genetic models. Our findings indicated that
GIPR
rs1800437 genotypes were associated with an increased risk of alcohol dependence. Statistically significant association between
GIPR
rs1800437 GG genotype and Brief Social Phobia Scale scores were observed in the abstinent alcohol-dependent patients, while
GLP1R
rs6923761 GG genotype was associated with Zung anxiety scores in healthy controls. Our pilot study indicates that
GIPR
rs1800437 may play some role in susceptibility to alcohol dependence, as well as in alcohol-related psychosymptomatology symptoms. To our knowledge, this is the first study that indicates the involvement of
GIPR
in alcohol dependence. However, studies with larger cohorts are needed to confirm these preliminary findings.
The Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) is a multidimensional rating scale for the assessment of drug-induced extrapyramidal symptoms (EPS), developed in 1994. It is suitable for ...evaluating EPS considering the degree of influence EPS has on daily activities and the subjective distress that it causes.
This study to evaluate the interrater and test-retest reliability of the DIEPSS Slovenian version conducted at the University Medical Center Maribor in Slovenia in November 2018.
Six raters performed the interrater assessment of 135 DIEPSS video clips with recordings of patients with EPS. A second assessment was then performed by 2 raters to evaluate the test-retest reliability, which was high (interclass correlation coefficients from 0.743 to 0.936).
The results for the Slovenian language version of the DIEPSS show high interrater and test-retest reliability, with high concordance rates for all evaluated items (interclass correlation coefficient > 0.8).
Background. Alcohol addiction is a very common and complex disease. Alcohol addicted patients have a high risk for developing comorbid psychiatric disorder. Methods. In the present study, we explored ...symptom expression and severity for the most common comorbid mental disorders in Slovenian alcohol addicted patients. Three groups of male subjects were included: 101 acutely alcohol-addicted inpatients, 100 former alcohol-addicted subjects and 97 healthy controls from a blood donors group. The following questionnaires were employed: AUDIT, Zung Depression and Anxiety scale, Brief Social Phobia Scale, Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Drinking Scale, and Buss-Durkee Hostility Inventory. Results. Acutely addicted patients showed significantly more obsessive (p<0.001) and compulsive (p<0.001) symptoms and also more obsessive-compulsive symptoms of relying on alcohol consumption (p<0.001) compared to the other two groups. Acutely addicted patients showed significantly more anxiety (p<0.001) as well as depressive (p<0.001) and aggressive (p<0.001) traits compared to the other two groups. Conclusions. Obsessive-compulsive, anxious, depressive and aggressive traits can be comorbidities associated with alcohol addiction. Increased attention to these symptoms during the treatment of alcohol addiction could result in better outcome of alcohol addiction treatment and lower relapse rate
Izhodišča. Zasvojenost od alkohola je zelo pogosta in kompleksna bolezen. Zasvojeni od alkohola imajo veliko tveganje za pojav sopojavne psihiatrične motnje. Metode. V prvi tovrstni slovenski raziskavi smo preverili prisotnost in izraženost simptomatike najpogostejših sopojavnih duševnih motenj pri zasvojenih od alkohola. Vključili smo tri skupine moških: 101 preiskovanca, hospitaliziranega zaradi zdravljenja akutne zasvojenosti od alkohola, 100 abstinentnih preiskovancev in 97 zdravih kontrol iz skupine prostovoljnih krvodajalcev. Za oceno simptomatike smo uporabili vprašalnike AUDIT, Yale-Brownovo lestvico obsesivnosti in kompulzivnosti ter lestvico obsesivno-kompulzivnega pitja, Zungovo lestvico depresivnosti in anksioznosti, Kratko lestvico socialne fobije in Buss-Durkeejevo lestvico sovražnosti. Rezultati. V skupini preiskovancev z akutno zasvojenostjo so bili pomembno bolj izražene obsesivna (p < 0,001) in kompulzivna simptomatika (p < 0,001) ter obsesivno-kompulzivna simptomatika, vezana na pitje alkoholnih pijač (p < 0,001), kot v preostalih dveh skupinah. Pri preiskovancih z akutno zasvojenostjo so bile v primerjavi z abstinenti in zdravimi kontrolami statistično pomembno bolj izražene anksioznost (p < 0,001), depresivnost (p < 0,001) in agresivnost (p < 0,001). Zaključki. Obsesivno-kompulzivna simptomatika, anksioznost, depresivnost in agresivnost so lahko sopojavno vezane na zasvojenost od alkohola. Med zdravljenjem zasvojenosti od alkohola je zato treba pozornost usmeriti tudi na te simptome, saj tako lahko bistveno izboljšamo izid zdravljenja zasvojenosti od alkohola in zmanjšamo tveganje za relaps
The present study explored whether specific single-nucleotide polymorphisms in alcohol metabolic pathway are associated with alcohol dependence or alcohol-related psychopathological symptoms.
Three ...groups of male unrelated subjects were included: 101 currently alcohol-dependent patients, 100 formerly alcohol-dependent subjects and 97 healthy controls. The following questionnaires were implemented: AUDIT, Zung Depression and Anxiety scale, Brief Social Phobia Scale, Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Drinking Scale and Buss-Durkee Hostility Inventory. All the subjects were genotyped for CYP2E1 c.-1053C>T and CAT c.-262C>T.
Statistically significant differences in the distribution of genotypes and alleles for CAT c.-262C>T polymorphism were observed among the three investigated groups. We observed a higher frequency of CAT -262T allele in alcohol-dependent subjects (OR = 1.74, 95% CI = 1.164-2.610). Among currently dependent patients CAT -262T allele carriers had higher AUDIT scores (P = 0.023), while CYP2E1-1053T allele carriers had significantly higher YBOCS-obsession subscale scores (P = 0.005) and Zung Anxiety Scale scores (P = 0.011).
Our findings suggest that the CAT c.-262C>T genetic polymorphism influences the susceptibility to alcohol dependence and severity of alcohol dependence, while CYP2E1 c.-1053C>T polymorphism influences the expression of obsessive-compulsive and anxiety symptoms.
Genes involved in the serotonin pathway may determine the susceptibility to alcohol dependence and its severity. The present study explored whether specific polymorphisms in the serotonin pathway ...could be associated with alcohol dependence or alcohol-related psychopathological symptoms.
The cohort comprised 101 currently and 100 formerly alcohol-dependent males, as well as 97 male healthy blood donors. The following questionnaires were employed: the Alcohol Use Disorders Identification Test, the Zung Depression and Anxiety Scale, the Brief Social Phobia Scale, the Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Drinking Scale, and the Buss-Durkee Hostility Inventory. Subjects were genotyped for bi- and triallelic SLC6A4 5-HTTLPR,HTR1A rs6295, and HTR1B rs13212041.
Statistical differences in bi- and triallelic SLC6A4 5-HTTLPR genotype distribution were observed between the 3 groups investigated (p = 0.008 and p = 0.023, respectively); however, no gene-dose effect was observed. The severity of the alcohol problems was higher in currently alcohol-dependent subjects with the 5-HTTLPR LL (p = 0.039) and L′L′ genotypes (p = 0.027). Formerly dependent subjects with the 5-HTTLPR S′S′ genotype showed more social anxiety, depressive, and anxiety traits (p = 0.009, p = 0.006, and p = 0.036, respectively). Healthy controls with the 5-HTTLPR SS genotype showed more traits of social anxiety (p = 0.020).
Our findings suggest that bi- and triallelic SLC6A4 5-HTTLPR has some effects on the severity of alcohol dependence. Triallelic 5-HTTLPR was associated with social anxiety, anxiety, and depressive traits in alcohol-dependent subjects.
Izhodišča. Zasvojenost od alkohola je zelo pogosta in kompleksna bolezen. Zasvojeni od alkohola imajo veliko tveganje za pojav sopojavne psihiatrične motnje. Metode. V prvi tovrstni slovenski ...raziskavi smo preverili prisotnost in izraženost simptomatike najpogostejših sopojavnih duševnih motenj pri zasvojenih od alkohola. Vključili smo tri skupine moških: 101 preiskovanca, hospitaliziranega zaradi zdravljenja akutne zasvojenosti od alkohola, 100 abstinentnih preiskovancev in 97 zdravih kontrol iz skupine prostovoljnih krvodajalcev. Za oceno simptomatike smo uporabili vprašalnike AUDIT, Yale-Brownovo lestvico obsesivnosti in kompulzivnosti ter lestvico obsesivno-kompulzivnega pitja, Zungovo lestvico depresivnosti in anksioznosti, Kratko lestvico socialne fobije in Buss-Durkeejevo lestvico sovražnosti. Rezultati. V skupini preiskovancev z akutno zasvojenostjo so bili pomembno bolj izražene obsesivna (p < 0,001) in kompulzivna simptomatika (p < 0,001) ter obsesivno-kompulzivna simptomatika, vezana na pitje alkoholnih pijač (p < 0,001), kot v preostalih dveh skupinah. Pri preiskovancih z akutno zasvojenostjo so bile v primerjavi z abstinenti in zdravimi kontrolami statistično pomembno bolj izražene anksioznost (p < 0,001), depresivnost (p < 0,001) in agresivnost (p < 0,001). Zaključki. Obsesivno-kompulzivna simptomatika, anksioznost, depresivnost in agresivnost so lahko sopojavno vezane na zasvojenost od alkohola. Med zdravljenjem zasvojenosti od alkohola je zato treba pozornost usmeriti tudi na te simptome, saj tako lahko bistveno izboljšamo izid zdravljenja zasvojenosti od alkohola in zmanjšamo tveganje za relaps
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