Efficacy of a Web-Based Screening and Brief Intervention to Prevent Problematic Alcohol Use in Korea: Results of a Randomized Controlled Trial.

BACKGROUND: Web-based alcohol screenings and brief interventions have been shown to be effective methods for changing drinking behavior. This study evaluated the efficacy of the online-based Brief Empowerment Program for Alcohol-Use Monitor (on-BEAM), a brief intervention applying personalized normative feedback (PNF) and components of motivational interviewing (MI) techniques. METHODS: A community-based, double-blind, parallel-group randomized controlled trial with individual randomization was conducted in Korea (registered at Clinical Research Information Service-KCT0003050). An e-mail about participating in a survey on drinking behavior was sent to 5,684 individuals, aged 20 to 40, that were registered as part of a research panel. Male and female participants with AUDIT-C scores of ≥4 and ≥3, respectively, were randomly assigned to either an intervention (received a drinking behavior assessment and the results with normative feedback) or control group (assessment and results without normative feedback). To evaluate the effects of the intervention with 2 sessions over the course of a month, a follow-up assessment was performed online 4 weeks after completion of the intervention. The main outcome was the number of standard drinks consumed during the past week measured using the timeline followback method. The rate ratios (RRs) were calculated to test the effects of the intervention. RESULTS: In total, 1,496 participants were randomized and 93% of them followed up. The intervention group reported consuming less alcohol during the past week (RR = 0.13; p = 0.012) than the control group. Additionally, the intervention group had fewer binge drinkers (RR = 0.69; p < 0.001) and a lower AUDIT-C score (RR = 0.59; p = 0.009) than the control group. CONCLUSIONS: The web-based intervention, on-BEAM, which applies PNF and MI components related to high-risk drinking reduced the amount of alcohol consumption in our study population. Further research is needed to determine the duration of on-BEAM's effects and evaluate its effectiveness in the real world.

Differential activation of face memory encoding tasks in alcohol-dependent patients compared to healthy subjects: an fMRI study.

It has been hypothesized that the right hemisphere of the brain is more sensitive to alcohol-related damage than the left hemisphere. The present study tested this hypothesis, using functional MRI to determine whether the pattern for right hemispheric activity is different for alcohol-dependent patients, compared to normal healthy individuals. Two different types of memory encoding tasks were performed separately: word and face encoding for both alcohol-dependent patients and normal healthy volunteers. The data for the normal volunteers indicate that the left prefrontal region is more active during word encoding, whereas the right parahippocampal region is more active during face encoding. The results for the patient data, however, demonstrated left lateralization in the prefrontal area during word encoding, while right lateralization in the parahippocampal region during face encoding was not observed. Therefore, alcoholism appears to have no influence on left hemispheric activity, since the activation pattern was similar to that observed for normal healthy persons. However, the absence of right hemispheric lateralization in alcohol-dependent patients is consistent with the hypothesis that the right hemisphere is more vulnerable to alcohol-related damage than the left hemisphere.

Clinical manifestation of alcohol withdrawal symptoms related to genetic polymorphisms of two serotonin receptors and serotonin transporter.

AIM: The purpose of this study was to investigate the role of serotonergic genes in the development of alcohol dependence. The manifestation of alcohol withdrawal symptoms related to serotonergic polymorphisms in alcoholics was also examined. METHODS: The role of polymorphisms in the serotonin receptor 1A (5-HT1A), serotonin receptor 2A (5-HT2A), and the serotonin transporter gene (5-HTT) promotor region (5-HTTLPR) in the manifestation of individual alcohol withdrawal symptoms was investigated in 97 Korean male inpatients with alcohol dependence and 76 Korean healthy male subjects. The patient's alcohol withdrawal symptoms were assessed with the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar) scale. RESULTS: In the 5-HT1A receptor, the frequency of G- genotype (CC) was significantly higher in patients with alcohol dependence than in normal controls (chi(2) = 5.03, p = 0.025). The CIWA-Ar subscale scores of nausea, anxiety, and headache, and total CIWA-Ar scale scores were significantly higher in G+ genotypes (CG+ GG) than in G- genotype (p = 0.005, p = 0.004, p = 0.008, and p = 0.008, respectively). CONCLUSION: The results suggest that the genetic polymorphism of the 5-HT1A receptor may play a role in alcohol dependence and polymorphisms of serotonergic genes may be important in withdrawal symptoms of patients with alcohol dependence.

Regional cerebral blood flow in patients with alcohol-related dementia: a SPECT study.

The purpose of this study was to investigate regional cerebral blood flow (rCBF) changes using 1110 MBq of Tc-99m ECD SPECT in alcohol-related dementia (ARD) patients. Twenty-five patients with ARD and 22 healthy control subjects were included in the study. Mini-Mental Status Examination was applied to the patients and controls. The ARD patients showed drastically reduced rCBF in the frontal cortices, basal ganglia, and thalami. The results indicate that ARD is associated with hypoperfusion in both cortical and subcortical regions. These findings support previous studies suggesting the association with both cortical and subcortical neuropathology in ARD patients.

Genetic association of DRD2 polymorphisms with anxiety scores among alcohol-dependent patients.

The dopaminergic neurotransmission system is one of the major factors in development of alcoholism and also contributes to anxiety and depression. In this study, the associations of the dopamine receptor type 2 (DRD2) polymorphisms with the symptoms of anxiety were analyzed. A total of 573 alcoholics and 273 controls were enrolled in the study from the Korean population. Five DRD2 SNPs, including -32869 A>G, -32768 insdel C, +11890 C>G, +11915 C>T, and +32806 C>T, were genotyped using a TaqMan assay and analyzed with various alcoholic phenotypes. Although no DRD2 polymorphisms were associated with the risk of alcoholism, +32806C>T and Block2-ht1 showed associations (in dominant models) with both the state anxiety level scale (STAI-S) and the trait anxiety level scale (STAI-T) (P=0.004 and P=0.003, and P=0.01 and P=0.005, respectively). In addition, the -32768 insdel C also showed positive association with both anxiety level scales in recessive models (P=0.01 and P=0.02, respectively).

Effect of genetic polymorphisms on smoking cessation: a trial of bupropion in Korean male smokers.

BACKGROUND: Even though bupropion is first-line pharmacological agent for smoking cessation, not all the smokers successfully quit smoking by bupropion. It means other factors like genetic predisposition could contribute to the therapeutic outcome. OBJECTIVES: The aim of this study is to elucidate the question of whether the abstinence rates by bupropion trial would be different depending on the genotypes. METHODS: Six candidate genes, thought to be involved in the interaction of nicotine and bupropion (for example, the dopamine receptor type 2, dopamine transporter, norepinephrine transporter, serotonin transporter, catecholamine-O-methyltransferase), and the clinical outcomes of smoking behavior were investigated. The participants were 225 male smokers to whom 150 mg of bupropion SR was administered for 4 weeks. The abstinence rates of specific genotypes were also compared. MAIN RESULTS: The results are as follows: (a) the frequencies of the A1/A2 genotype of the dopamine receptor type 2 TaqI A gene and SLC6A3-9 genotype of the dopamine transporter 1 gene were higher in the nonabstinence group than in the abstinence group (chi2=20.40, P<0.01 for A1/A2, chi2=7.76, P=0.01 for SLC6A3-9). The frequencies of the COMTH/COMTH and A/G genotypes of the norepinephrine transporter gene were higher in the abstinence group than in the nonabstinence group (chi2=8.12,P=0.02 for COMTH/COMTH, chi2=3.04, P<0.01 for A/G). (b) Participants having specific genotypes such as homozygotes (A1/A1 or A2/A2) of DRD2 TaqI A, COMTH/COMTH, AG of NET-8, and LL of 5-HTTLPR showed a higher abstinence rate than the other participants. CONCLUSIONS: It can be concluded that genetic diversity might determine the effects of bupropion on smoking cessation.

Increased leptin and decreased ghrelin level after smoking cessation.

Smoking cessation is associated with transient increases in body weight. Leptin and ghrelin are known to be major mediators of appetite, weight and the reward pathway. Therefore, this study assessed the changes in the plasma leptin and ghrelin level and their relationship with the body weight and appetite after smoking cessation in the Korean population. Eighteen subjects, who had stopped smoking for 2 months were enrolled in this study. The body mass index (BMI), body fat mass (BFM), waist-hip ratio (WHR), weight and appetite were measured before and after smoking cessation. In addition, the plasma leptin and ghrelin levels were measured. The BMI, BFM, WHR, weight and appetite were significantly higher than baseline in those who had gave up smoking for 2 months (p<0.05). The plasma leptin concentration increased and the plasma ghrelin level decreased after smoking cessation. The change in the leptin level was positively correlated with the change in the body mass index and body fat mass. These results do not support the direct mediation of the leptin-ghrelin-neuropeptide Y (NPY) system on weight gain after smoking cessation. It appears that weight and appetite is regulated by a more complicated mechanism after smoking cessation.

Changes of smoking behavior and serum adrenocorticotropic hormone, cortisol, prolactin, and endogenous opioids levels in nicotine dependence after naltrexone treatment.

This study was done to evaluate the therapeutic effects of naltrexone on smoking behaviors and to measure the changing of brain substances for elucidating the mode of action by naltrexone. Twenty-five voluntarily participated healthy male smokers were randomly assigned to naltrexone group or placebo group for 2 weeks. In this study, naltrexone group showed significant reduction in daily cigarette consumption amount, the expiratory CO levels, brief questionnaire for smoking urge (B-QSU) score, and FTQ score. However, only 2 subjects in naltrexone group quitted smoking completely at 4th week. Plasma levels of pituitary hormones (ACTH, cortisol, and prolactin) and endogenous opioids (beta-endorphin and dynorphin A) were checked weekly before and after the 'provocation and smoking coupled' stimulus once in a week for 3 weeks. In naltrexone group, pituitary hormones showed upward tendencies even though only the prolactin had statistical significance. However, beta-endorphin and dynorphin A were not significantly different between the two groups. It was suggested that naltrexone made effects on hypothalamo-pituitary-adrenocortical axis activity as well as smoking behavior. However, the meaning of these endocrinal changes by naltrexone is not conclusive, whether it is beneficial or aversive.

Standardization Study of the Korean Version of the Stages of Change Readiness and Treatment Eagerness Scale for Smoking Cessation (K-SOCRATES-S) and Its Predictive Validity.

OBJECTIVE: The purpose of the study was to develop the Korean version of the Stage of Change Readiness and Treatment Eagerness Scale for Smoking Cessation (K-SOCRATES-S) based on the Korean version of the Stages of Readiness for Change and Eagerness for Treatment scale (K-SOCRATES). This paper also demonstrates its reliability and validity among patients with nicotine dependence in South Korea. METHODS: At seven healthcare promotion centers in Gyeonggi-do, 333 male smokers aged 20 to 70 who visited smoking cessation clinic were recruited for this study and the K-SOCRATES-S was administered. After three months, the number of respondents who successfully stopped smoking was assessed by testing their urine cotinine level. Subsequently, exploratory factor analysis was performed to verify the reliability and validity of the K-SOCRATES-S. Also, a logistic regression analysis was performed to examine the variables that can predict the successful cessation of smoking on subscales of the K-SOCRATES-S. RESULTS: Exploratory factor analysis of the K-SOCRATES-S showed that the scale consisted of three factors: Taking Steps, Recognition, and Ambivalence. The scales measuring Taking Steps and Recognition in this scale had a significantly positive correlation with the scores observed on Kim's smoking cessation motivation scale. The scales measuring Taking Steps and Recognition had a significantly negative correlation with Ambivalence. Overall, the results indicate that the K-SOCRATES-K scale showed high validity. CONCLUSION: The K-SOCRATES-S developed in the present study is highly reliable and valid for predicting a patient's likelihood of success in quitting smoking among patients who want to cease smoking.

Validation Study of Kim's Smoking Cessation Motivation Scale and Its Predictive Implications for Smoking Cessation.

OBJECTIVE: The purpose of this study was to develop a scale to measure motivation for smoking cessation. Motivation is known to be important for success of smoking cessation. The reliability of the scale was assessed and its predictive validity for smoking cessation was evaluated. METHODS: We recruited 333 men aged 20 to 70 that visited smoking cessation clinics at seven public health centers. The demographic characteristics were recorded and the Korean version of Stages of Readiness for Change and Eagerness for Treatment Scale for Smoking (K-SO-CRATES-S) performed. A smoking cessation motivation scale was developed with 10 questions based on the theory of motivation enhancement therapy. RESULTS: The motivation scale was composed of four subscales based on the factor analysis; each subscale had an adequate degree of internal consistency. In addition, the newly developed scale had a high degree of validity based on its significant correlation with the smoking version of SOCRATES. Moreover, the precontemplation level of motivation was found to significantly predict the success of smoking cessation. And one of the subscales of the Korean Nicotine Dependence Syndrome Scale (K-NDSS), stereotypy which also significantly predicted the success of smoking cessation, significantly correlated with the preparation 1 and 2 level of motivation. CONCLUSION: The smoking cessation motivation scale with 10 questions that was developed in this study was a highly reliable and valid scale for the prediction of success for smoking cessation for those who wanted to stop smoking.

The effect of 12-week open-label memantine treatment on cognitive function improvement in patients with alcohol-related dementia.

There is compelling evidence that alcohol-induced neurotoxicity is related to glutamate excitotoxicity. It was hypothesized that the low-affinity NMDA receptor antagonist memantine would improve the cognitive function of patients with alcoholic dementia. The aim of this study was to test this hypothesis and to evaluate the effect of memantine on the cognitive improvement of patients with alcohol-related dementia (ARD). The study was designed as a 12-wk open-label study investigating the efficacy of 20 mg memantine, a low-affinity NMDA receptor antagonist, as a treatment for cognitive and behavioural problems in 19 patients with probable ARD according to the criteria for ARD proposed by Oslin and colleagues. The CERAD-K (Consortium to Establish a Registry for Alzheimer's Disease - Korean version) and several clinical assessment scales were completed before and after the 12-wk memantine treatment period. Significant improvements in the mean scores from baseline to final assessment were observed in the Global Deterioration Scale (p<0.05), Brief Psychiatric Rating Scale (p<0.01), Geriatric Quality of Life - Dementia scale (p<0.01) and Neuropsychiatric Inventory (p<0.01) at the end of week 12. The CERAD-K subscales of word list recall (p<0.05), word list recognition (p<0.05), time orientation (p<0.01), drawing an interlocking pentagon (p<0.05), and the total MMSE-K (Mini Mental State Examination - Korean version) scores (p<0.01) of the patients all showed significant improvement following the memantine trial. In this open-label study, patients with ARD treated with 20 mg/d memantine for 12 wk showed improvement on global cognition, quality of life and behavioural symptoms. The result of this study suggests the possible usefulness of memantine for the treatment of ARD. As this was an open-label study, the possibility that participants improved cognitively on their own due to protracted abstinence from alcohol cannot be discounted.

Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence.

BACKGROUND: Many reports have suggested possible relationships between brain-derived neurotrophic factor (BDNF) and alcohol dependence. A protective effect of BDNF against ethanol-induced cell damage has been suggested, and this effect may contribute to the development or maintenance of alcohol dependence. This study was carried out in order to verify the significance of BDNF in alcohol dependence. METHODS: Peripheral BDNF levels were measured in alcohol-dependent patients and control subjects using an enzyme-linked immunosorbent assay. A physician's interview and standardized questionnaire were used to obtain information regarding each patient's history of alcohol consumption. RESULTS: The mean BDNF level was lower in the alcohol dependence group (389.5 +/- 501.7 pg/ml) than in the normal controls (822.5 +/- 420.7 pg/ml) by analysis of covariance (ANCOVA) (F = 25.79, p < 0.01). The mean BDNF level was lower in the alcohol-dependent patients with a positive family history of alcohol dependence (247.6 +/- 289.2 pg/ml) than in those with a negative family history of alcohol dependence (583.9 +/- 652.8 pg/ml) by ANCOVA (F = 6.51, p = 0.01). The BDNF levels did not correlate significantly with any of the variables analyzed in this study, including Beck depression inventory, state and trait anxiety inventory (STAI-S and T), and various drinking behaviors. CONCLUSIONS: Changes in the levels of BDNF might play a role in the pathophysiology and inheritance of alcohol dependence.

5' UTR polymorphism of dopamine receptor D1 (DRD1) associated with severity and temperament of alcoholism.

Multiple dopamine receptors in the dopaminergic system may be prime candidates for genetic influence on alcohol abuse and dependence due to their involvement in reward and reinforcing mechanisms. Genetic polymorphisms in dopamine receptor genes are believed to influence the development and/or severity of alcoholism. To examine the genetic effects of the Dopamine Receptor D1 (DRD) gene family (DRD1-DRD5) in the Korean population, 11 polymorphisms in the DRD gene family were genotyped and analyzed in 535 alcohol-dependent subjects and 273 population controls. Although none of the polymorphisms of DRD1-5 genes were found to be associated with the risk of alcoholism, one 5' UTR polymorphism in the DRD1 (DRD1-48A>G) gene was significantly associated with severity of alcohol-related problem, as measured by the Alcohol Use Disorders Identification Test (AUDIT) in a gene dose-dependent manner, i.e., 24.37 (+/-8.19) among patients with -48A/A genotype, 22.37 (+/-9.49) among those with -48A/G genotype, and 17.38 (+/-8.28) among those with -48G/G genotype (P=0.002). The genetic effects of DRD1-48A>G were further analyzed with other phenotypes among alcohol-dependent subjects. Interestingly, the DRD1-48A>A genotype was also found to be associated with novelty seeking (NC), harm avoidance (HA), and persistence (P) (P =0.01, 0.02, and 0.003, respectively). The information derived from this study could be valuable for understanding the genetic factors involved in alcoholic phenotypes and genetic distribution of the DRD gene family, and could facilitate further investigation in other ethnic groups.