Myung Hun Jung

Alcohol and Cognition in the Elderly: A Review

Consumption of large amounts of alcohol is known to have negative effects, but consumption in smaller amounts may be protective. The effect of alcohol may be greater in the elderly than in younger adults, particularly with regard to cognition. However, the drinking pattern that will provide optimal protection against dementia and cognitive decline in the elderly has not been systematically investigated. The present paper is a critical review of research on the effect of alcohol on cognitive function and dementia in the elderly. Studies published from 1971 to 2011 related to alcohol and cognition in the elderly were reviewed using a PubMed search. Alcohol may have both a neurotoxic and neuroprotective effect. Longitudinal and brain imaging studies in the elderly show that excessive alcohol consumption may increase the risk of cognitive dysfunction and dementia, but low to moderate alcohol intake may protect against cognitive decline and dementia and provide cardiovascular benefits. Evidence suggesting that low to moderate alcohol consumption in the elderly protects against cognitive decline and dementia exists; however, because of varying methodology and a lack of standardized definitions, these findings should be interpreted with caution. It is important to conduct more, well-designed studies to identify the alcohol drinking pattern that will optimally protect the elderly against cognitive decline and dementia.

Artificial microRNA-based neurokinin-1 receptor gene silencing reduces alcohol consumption in mice

In the brain, the stress system plays an important role in motivating continued alcohol use and relapse. The neuropeptide substance P and the neurokinin-1 receptor (NK1R) are involved in the stress response and drug reward systems. Recent findings have shown that the binding of ligands to NK1Rs decreases the self-administration of alcohol in mice. We examined the effect of an artificial microRNA (amiRNA) on the functional expression of NK1R in mouse brains. Lentiviruses expressing either an amiRNA targeting the NK1R (amiNK1R) or a negative control amiRNA (amiNC) were injected into mouse brains. Four weeks after amiRNA injection, we found that amiNK1R decreased the voluntary alcohol consumption compared to mice injected with amiNC. We also observed that NK1R expression was reduced in the hippocampus. RNA interference is an effective approach to regulate the expression of specific behavior-related genes. Our results support the potential use of amiRNA as a therapeutic agent for the treatment of alcohol dependence.

Epigenetic Changes of Serotonin Transporter in the Patients with Alcohol Dependence: Methylation of an Serotonin Transporter Promoter CpG Island

Objective Psychiatric disorders such as depression, anxiety and alcohol dependence are associated with serotonin metabolism. We assessed the methylation level of the serotonin transporter (5-HTT) promoter region in control and alcohol dependent patients. Methods Twenty seven male patients who met the Diagnostic and Statistical Manual of Mental Disorder IV (DSM-IV) criteria for alcohol dependence were compared with fifteen controls. Polymerase chain reaction (PCR) assays of bisulfate-modified DNA were designed to amplify a part of the CpG island in the 5HTT gene. Pyrosequencing was performed and the methylation level at seven CpG island sites was measured. Results We found no differences in the methylation patterns of the serotonin transporter linked promoter region (5-HTTLPR) between alcohol-dependent and control subjects. Conclusion Our negative finding may be because 5-HTT epigenetic variation may not affect the expression for 5-HTT or there may be other methylation site critical for its expression. To find out more conclusive result, repeating the study in more methylation sites with a larger number of samples in a well-controlled setting is needed.

Association of CHRM2 polymorphisms with severity of alcohol dependence.

The cholinergic muscarinic 2 receptor (CHRM2) gene has been considered a candidate gene for the alcohol dependence in that it might underpin certain risk factors for this condition. This study examined variations in the CHRM2 between the patients with alcohol dependence and population controls in Korean and explored the associations between CHRM2 polymorphisms and severity of symptoms in the patients with alcohol dependence. One hundred and fifty‐five patients with alcohol dependence, defined by the Alcohol Use Disorders Identification Test (AUDIT) and the Alcohol Dependence Scale (ADS) to measure the severity of symptoms, and one hundred and ninety‐five population controls were drawn in the study. Three single nucleotide polymorphisms (SNPs) of CHRM2 were genotyped using the TaqMan assay and analyzed with the severity of symptoms of alcohol dependence. We found that although SNP rs324650 showed marginal association with the risk of alcohol dependence (P = 0.03), the significance of the result was not sustained after multiple corrections. SNP rs1824024 was significantly associated with the AUDIT and ADS scores in patients (P = 0.005 and 0.003, respectively). These findings suggested that the muscarinic acetylcholine function might be related not with alcohol dependence itself but with the severity of alcohol dependence in Korean population.

Depression, aggression, and suicidal ideation in first graders: a school-based cross-sectional study

OBJECTIVE This study explored the clinical characteristics and risk factors of suicidal ideation in a sample of first graders from South Korea. Childrens depression and aggression and maternal depression were examined as possible risk factors. METHODS This study is a school-based, cross-sectional study of 5 elementary schools in Gunpo City, South Korea. Participants were 707 first graders (mean age, 6.54 years) and their mothers. We assessed childrens depressive and aggressive symptoms using the Behavior Assessment System for Children-2 (BASC-2) and maternal depression using the Beck Depression Inventory (BDI). Two items from BASC-2 and 1 item from BDI identified childrens and maternal suicidal ideation. RESULTS Twenty-seven (3.8%) children evidenced suicidal ideation. Children with suicidal ideation had higher mean scores of depression domain (10.11 ± 5.34 vs 4.57 ± 3.44, P < .0001) and aggression domain (7.78 ± 3.84 vs 3.80 ± 2.85, P < .0001) on BASC-2 and maternal depression (9.78 ± 6.45 vs 7.28 ± 5.38, P = .02) on BDI. In regression analysis, childrens depression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.32; P = .001) and aggression (OR, 1.24; 95% CI, 1.08-1.41; P = .002) contributed significantly to childrens suicidal ideation, whereas maternal depression was not significantly related to childrens suicidal ideation (OR, 0.99; 95% CI, 0.92-1.06; P = .75). CONCLUSIONS This study demonstrated that even first graders had a considerable prevalence of suicidal ideation and that depression and aggression were associated with suicidal ideation in young children.

Decreased connectivity of the default mode network in pathological gambling: a resting state functional MRI study.

The default mode network (DMN) represents neuronal activity that is intrinsically generated during a resting state. The present study used resting-state fMRI to investigate whether functional connectivity is altered in pathological gambling (PG). Fifteen drug-naive male patients with PG and 15 age-matched male control subjects participated in the present study. The pathological gambling modification of the Yale-Brown Obsessive Compulsive Scale (PG-YBOCS), the Beck Depression Inventory, and the Beck Anxiety Inventory were used to determine symptom severity in all participants. Participants were instructed to keep their eyes closed and not to focus on any particular thoughts during the 4.68-min resting-state functional scan. The patients with PG displayed decreased default mode connectivity in the left superior frontal gyrus, right middle temporal gyrus, and precuneus compared with healthy controls. The severity of PG symptoms in patients with PG was negatively associated with connectivity between the posterior cingulate cortex seed region and the precuneus (r=-0.599, p=0.018). Decreased functional connectivity within DMN suggests that PG may share similar neurobiological abnormalities with other addictive disorders. Moreover, the severity of PG symptoms was correlated with decreased connectivity in the precuneus, which may be important in the response to treatment in patients with PG.

The Effectiveness of Continuing Group Psychotherapy for Outpatients with Alcohol Dependence: 77‐Month Outcomes

BACKGROUND Group psychotherapy (PT) is one of the most common interventions used to treat alcohol dependence (AD), and it is assumed to be effective. Despite its common clinical use, long-term trials that have been conducted to examine the efficacy of group PT in the treatment of outpatients with AD are limited and often lack appropriate comparisons. On that basis, a long-term comparative trial was performed with the main objective of evaluating the effectiveness of continuing group PT for outpatients with AD. METHODS Quasi-experimental trial was conducted from January 2004 to May 2010 in 177 AD subjects who had completed an inpatient 10-week alcohol treatment program. Abstinence rates of the combined group (experimental group: outpatient individual PT plus group PT, N = 94) and the standard outpatient individual PT-only group (comparison group, N = 83) were statistically compared using Kaplan-Meier survival analysis. Predictive factors of abstinence rate for alcohol were assessed using Cox regression analysis. RESULTS Abstinence rates of the combined PT group were significantly high relative to those of the outpatient individual PT-only group. Significant predictive factors for the alcohol abstinence rate were outpatient group PT and age. Even after controlling for confounding factors, outpatient group PT was a significant predictive factor for the alcohol abstinence rate. CONCLUSIONS Our findings indicate that for AD patients who had completed an inpatient 10-week alcohol treatment, outpatient group PT appears to be an effective form of continuing care or aftercare within the context of an outpatient service delivery system.

The Genetic Effect of Copy Number Variations on the Risk of Alcoholism in a Korean Population

BACKGROUND Alcoholism, a chronic behavioral disorder characterized by excessive alcohol consumption, has been a leading cause of morbidity and premature death. This condition is believed to be influenced by genetic factors. As copy number variation (CNV) has been recently discovered in human genome, genomic diversity of human genome is more frequent than previously thought. Many studies have reported evidences that CNV is associated with the development of complex diseases. In this study, we hypothesized that CNV can predict the risk of alcoholism. METHODS Using the Illumina HumanHap660W-Quad BeadChip (∼660 k markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 116 alcoholic cases and 1,022 healthy controls (total n = 1,138) in a Korean population. To identify alcoholism-associated CNV regions, we performed a genome-wide association analysis, using multivariate logistic regression model controlling for age and gender. RESULTS We identified a total of 255,732 individual CNVs and 3,261 CNV regions (1,067 common CNV regions, frequency > 1%) in this study. Results from multivariate logistic regression showed that the chr20:61195302-61195978 regions were significantly associated with the risk of alcoholism after multiple corrections (p = 5.02E-05, p(corr) = 0.04). Most of the identified variations in this study overlapped with the previously reported CNVs in the Database of Genomic Variants (95.3%). The identified CNVs, which encompassed 3,226 functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the cell part, in developmental processes, in cell communication, in neurological system process, in sensory perception of smell and chemical stimulus, and in olfactory receptor activity. CONCLUSIONS This is the first genome-wide association study to investigate the relationship between common CNV and alcoholism. Our results suggest that the newly identified CNV regions may contribute to the development of alcoholism.

Past suicidal ideation as an independent risk factor for suicide behaviours in patients with depression

Abstract Objectives: As South Korea has the highest incidence of completed suicides, the present study aimed to investigate the predictive power of the variables that have been associated with suicide attempts in Korean patients diagnosed with depression. Methods: Hundred participants were divided into two groups: suicide attempters (31%) and suicide non-attempters (69%). Participants with a history of more than one suicidal attempt were assigned to the suicide attempter group. A hierarchical logistic regression analysis was performed to determine the predictive strengths of the variables that were likely to be associated with suicide attempts. Results: After controlling for the effects of such variables as the severity of depressive symptoms, life stress events and impulsivity, the severity of past suicidal ideation was the most important predictive factor for discriminating suicide attempters from suicide non-attempters. The odds ratio for attempting suicide relative to not attempting suicide increased by a factor of 4.408 for each unit of increase in suicidal ideation. Conclusions: The present study suggests that the most severe suicidal ideation throughout one’s entire life should not be overlooked and may be a major predictor of the risk of suicide.

Efficacy and Tolerability of Paliperidone Extended-release in the Treatment of First-episode Psychosis: An Eight-week, Open-label, Multicenter Trial

Objective We investigated the efficacy and tolerability of paliperidone extended-release (ER) tablets in patients with first-episode psychosis (n=75). Methods This was an 8-week, open-label, multicenter trial. The primary outcome variable was scores on the Positive and Negative Syndrome Scale (PANSS); secondary measures included the Scale for the Assessment of Negative Symptoms (SANS), the Cognitive Assessment Interview (CAI), and the Global Assessment of Functioning (GAF). To assess safety, we measured drug-related adverse events, weight, lipid-related variables, and prolactin and administered the Simpson–Angus Rating Scale (SARS), the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Scale (BAS), the Arizona Sexual Experiences Scale (ASEX), and the Udvalg for Kliniske Undersogelser side effect rating scale (UKU). Results The administration of paliperidone ER resulted in significant improvement in the PANSS, SANS, CAI, and GAF scores (p<0.001) over time. This improvement was evident as early as 1 week. The most frequent adverse events were akathisia, somnolence, anxiety, and sedation, which were well tolerated. Modest increases in weight and lipid profiles were also noted. Prolactin levels were substantially increased at the endpoint in both male and female patients. Conclusion These results indicate that paliperidone ER is effective and is characterized by good tolerability in the treatment of positive and negative symptoms and cognitive functioning in first-episode psychosis.