Effect of MAOA rs1465108 polymorphism on susceptibility to substance/alcohol use disorder: a novel PCR-RFLP assay for the detection of MAOA rs1465108.

BACKGROUND: The health and social consequences of substance/alcohol use disorders are harmful. Most of the individuals cannot stop using them due to more likely their genetic background. The current study aimed both to develop a novel PCR-RFLP method for genotyping of MAOA rs1465108 and to analyze the effect of MAOA rs1465108 on the risk of alcohol (AUD), opioid (OUD) or methamphetamine (MUD) use disorders and on the depressive and anxiety symptoms in a Turkish population. METHODS AND RESULTS: A total of 353 individual with AUD (n = 154), OUD (n = 160) or MUD (n = 39) and 109 healthy subjects were included. The intensity of anxiety and depressive symptoms and craving and opioid withdrawal were measured by appropriate scales. Logistic regression analysis revealed no association between MAOA rs1465108 polymorphism and substance/alcohol use disorder (p > 0.05). Healthy subjects (3.0) had significantly lower levels of depressive symptoms than individuals with OUD (27.0), AUD (21.0) and MUD (25.5) groups. The severity of depressive symptoms was significantly higher in OUD as compared to AUD. There was a statistically significant difference between individuals with AUD, OUD and MUD in view of the average ages of first use (17, 19 and 20 years, respectively) (p < 0.05). CONCLUSIONS: The results presented here do not support the hypothesis that MAOA rs1465108 is associated with substance/alcohol use disorders. The intensity of depressive symptoms could be changed according to the abused substance type. A novel PCR-RFLP was developed for genotyping of MAOA rs1465108 polymorphism, which could be a better option for laboratories without high technology equipment.

A case control study investigating the methylation levels of GHRL and GHSR genes in alcohol use disorder.

BACKGROUND: Alcohol use disorder (AUD) is a relapsing disease described as excessive use of alcohol. Evidence of the role of DNA methylation in addiction is accumulating. Ghrelin is an important peptide known as appetite hormone and its role in addictive behavior has been identified. Here we aimed to determine the methylation levels of two crucial genes (GHRL and GHSR) in ghrelin signaling and further investigate the association between methylation ratios and plasma ghrelin levels. METHODS: Individuals diagnosed with (n = 71) and without (n = 82) AUD were recruited in this study. DNA methylation levels were measured through methylation-sensitive high-resolution melting (MS-HRM). Acylated ghrelin levels were detected by ELISA. The GHRL rs696217 polymorphism was analyzed by the standard PCR-RFLP method. RESULTS: GHRL was significantly hypermethylated (P < 0.0022) in AUD between 25 and 50% methylation than in control subjects but no significant changes of GHSR methylation were observed. Moreover, GHRL showed significant positive correlation of methylation ratio between 25 and 50% with age. A significant positive correlation between GHSR methylation and ghrelin levels in the AUD group was determined (P = 0.037). The level of GHRL methylation and the ghrelin levels showed a significant association in the control subjects (P = 0.042). CONCLUSION: GHSR and GHRL methylation levels did not change significantly between control and AUD groups. However, GHRL and GHSR methylations seemed to have associations with plasma ghrelin levels in two groups. This is the first study investigating the DNA methylation of GHRL and GHSR genes in AUD.

Effect of PDYN and OPRK1 polymorphisms on the risk of alcohol use disorder and the intensity of depressive symptoms.

AIMS: The dynorphin (DYN)/Kappa Opioid Receptor (KOR) system has been suggested to be involved in both negative affective states and the action of alcohol. The present study was undertaken to explore whether the DYN/KOR system genes, PDYN and OPRK1, influence on individual differences in the intensity of depressive symptoms at admission as well as the risk of alcohol use disorder (AUD) risk in a sample of 101 individuals with AUD and 100 controls. METHODS: PDYN (rs2281285, rs2225749 and rs910080) and OPRK1 (rs6473797, rs963549 and rs997917) polymorphisms were analyzed by PCR-RFLP. The intensity of depressive and anxiety symptoms and craving were measured by the Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and Penn Alcohol Craving Scale, respectively. RESULTS: A significant association between the risk of AUD and OPRK1 rs6473797 (P < 0.05) at the gene level. OPRK1 rs6473797 CC genotype was found to lead to a 3.11 times greater alcohol dependence risk. In addition, the BDI-II score of the OPRK1 rs963549 CC genotype was found to be significantly lower (20.9 ± 11.2, min: 1.0, max: 48.0) than that of the CT + TT genotypes (27.04 ± 12.7, min: 0.0, max: 49.0) (t: -2.332, P = 0.022). None of the PDYN polymorphisms were associated with BDI-II score. CONCLUSION: Variations in the KOR are associated with the risk of AUD and the intensity of depressive symptoms at admission at the gene level in Turkish males. On the other hand, PDYN gene seemed not to be associated with AUD, depression, anxiety, and craving.

Association of PDYN 68-bp VNTR polymorphism with sublingual buprenorphine/naloxone treatment and with opioid or alcohol use disorder: Effect on craving, depression, anxiety and age onset of first use.

In this case-control study (423 Turkish subjects), the functional pro-dynorphin (PDYN) 68-bp VNTR polymorphism was genotyped in opioid users receiving sublingual buprenorphine/naloxone treatment (SBNT; n = 129, 119 males and 10 females), in opioid users (OUD; n = 99, 90 males and 9 females), in alcohol users (AUD; n = 75, 75 males) and in controls (n = 120, 109 males and 11 females) to determine the effect of this polymorphism on different treatment responses, heroin or alcohol dependence as well as age onset of first use. The PDYN 68-bp alleles were determined based on the number of repeats and genotypes were classified as "short/short (SS)", "short-long (SL)" and "long-long (LL)". The intensity of craving, withdrawal, depression and anxiety were measured by the Substance Craving Scale (SCS), the Clinical Opiate Withdrawal Scale (COWS), the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI), respectively. Healthy controls (5.5 ± 5.8) had significantly lower levels of depressive symptoms compared to OUD (25.4 ± 13.5), AUD (22.5 ± 11.3) and SBNT (19.29 ± 12.2) groups. In OUD group, the LL genotype was associated with decreased intensity of anxiety and depressive symptoms than the SS+SL genotype. The BDI-II scores for PDYN VNTR genotypes within the 4 groups were analysed by two-way ANOVA and statistical differences were found for the groups. SBNT group had significantly lower COWS score than OUD group (1.00 versus 3.00). There were statistically significant differences in the median BAI (11 versus 24) and BDI-II scores (17.5 versus 25) between OUD and SBNT groups, supporting the antidepressant and anxiolytic effects of SBNT in persons with OUD.

[A study on alcohol use among working youth who are continuing apprenticeship training]. / Ciraklik egitimine devam eden çalisan gençlerde alkol kullanimi üzerine bir çalisma.

OBJECTIVE: Considering both burden of entering working life and engaging in adult roles in terms of being employed, working youth forms a specific group to be handled regarding alcohol use problems. In this study it was aimed to investigate prevalence and patterns of alcohol use among youth in apprenticeship schools in central Ankara. METHOD: A survey was done to investigate presence of alcohol use problems among students of five apprenticeship schools in Ankara using CAGE Questionnaire and a questionnaire form including more detailed questions about alcohol use. RESULTS: Prevalence of life-time use of alcohol was 37.3% and prevalence of alcohol use more than once was 24.3%. Ten per cent of students with a history of alcohol use told that they went on drinking during last year. Proportion of students who continued drinking during the last year and getting at least 2+ score from CAGE was found as 4.5%. CONCLUSION: Prevalence of clinically significant alcohol use is quite high among working youth. Thus, in order to plan preventive measures, risk factors for alcohol use problems should be considered in detail in working youth.

Reliability and Validity of the Turkish Version of the Addiction Severity Index in Male Alcohol Dependents.

INTRODUCTION: We aimed to evaluate the psychometric characteristics of the Turkish translation of the Addiction Severity Index (ASI) in 115 male alcohol-dependent patients. METHOD: The reliability of the instrument was assessed by measuring test-retest, interrater and internal reliabilities. In the validity analysis, the correlation coefficients between corresponding severity ratings and composite scores of each subscale and concurrent validity were assessed. Moreover, the discriminant validity and concurrent validity scores were calculated. RESULTS: The test-retest reliability of the ASI scores ranged from .79 to .91. The interrater reliability assigned by three raters was high (.74 to .99). Cronbach's alpha coefficient for internal consistency was .85 for all scales, and it varied between .64 and .77 for the subscales. The Beck Depression Inventory moderately correlated with the Psychatric status, and the MacAndrew Alcoholism Scale correlated with the Alcohol and Drug Use subscales of the Addiction Severity Index (ASI). The correlation coefficient was .91 for the alcohol use subscale. CONCLUSION: The results obtained in this study suggest that the Turkish version of the ASI could be used as a reliable and valid instrument in alcohol-dependent patients.

Alcohol use prevalence and sociodemographic correlates of alcohol use in a university student sample in Turkey.

BACKGROUND: This study is a survey to determine prevalence and sociodemographic correlates of drinking problems among students from five university centres in Turkey. METHOD: Using an anonymous self-administered questionnaire and the CAGE Questionnaire for alcohol use problems, 1,720 students were surveyed. RESULTS: Of the whole student sample 63.3% reported that they had ever tried drinking alcohol, and 48.5% had used alcohol in the past year. Sixty five percent of the students had been drinking once a month or more frequently. The overall prevalence of alcohol use problems according to CAGE2+ was 9.7% (19.9% among the students who used alcohol in the past year). In multivariate analysis, male students tended to have problems with alcohol about three times more than females. Living in the dormitory seemed to be protective in terms of frequent drinking, and as educational level of the parents increased, the odds of drinking at least once a month increased. Students whose mothers were illiterate or primary school graduate tended to give more positive answers to the Cut-down, Annoyed and Guilty items. The odds of giving a positive answer to the Cut-down item among those living alone was greater than the other residence groups. Predictors of positive answer to the Eye-opener item were male gender, living alone at home, and residence of the family being in a foreign country. Paternal educational level being in the illiterate/primary school category was significantly related with more positive answers to the Guilty item. CONCLUSIONS: Drinking problems among university students in Turkey are more prevalent when compared with prevalence rates shown in other surveys in Turkey. Alternative ways of socialization should be provided for the university youth in order to prevent alcohol use problems in the future.

Alcoholic case of central pontine myelinolysis with mainly cerebellar signs.

The etiology of central pontine myelinolysis (CPM) is usually related to rapid correction of hyponatremia and alcoholism. Here a case with CPM predominated by cerebellar signs is described, and the neuropsychological assessment of the case is presented as well. Blood biochemistry revealed a normal sodium level and neuropsychological examination revealed impairment in attention and concentration, reduced immediate memory span, and impaired delayed recall. Further studies are needed to discover whether these neuropsychological signs are specific for CPM or due to alcoholism in general.