Sung-Gon Kim

Association of Functional Opioid Receptor Genotypes With Alcohol Dependence in Koreans

BACKGROUND The functional polymorphism (A118G) of the mu-opioid receptor gene (OPRM1) is thought to have clinical significance in the treatment of alcohol dependence. This study compared Koreans with one or two copies of the A118G polymorphism seeking treatment for alcohol dependence with a group of non-alcohol-dependent controls. METHODS Patients hospitalized for alcohol dependence (n = 112) and a group of non-alcohol-dependent controls (n = 140) were interviewed on aspects of drinking history and psychiatric history. Patients and controls were excluded if they met criteria for any other major psychiatric disorder. Participants were genotyped at the OPRM1 locus. RESULTS The allele frequency of the Asp40 allele was 0.397 in the alcohol-dependent group, which is consistent with other literature demonstrating this polymorphism to be common in Asian populations. Within the alcohol-dependent subjects, being homozygous for the Asp40 allele was associated with more days drinking than those heterozygous or homozygous for the Asn40 allele. Differences in the allele frequencies between alcohol-dependent and non-alcohol-dependent controls were not significant. CONCLUSIONS These results suggest that having one or two copies of the A118G allele is common among Koreans and may be an important genetic factor in the etiology of alcohol dependence and the frequency of alcohol consumption.

The effect of antagonists selective for μ- and δ-opioid receptor subtypes on alcohol consumption in C57BL/6 mice

Abstract Several studies have demonstrated that non-selective opioid receptor antagonists effectively reduce alcohol consumption in both animal models and at the clinical level. However, research examining the contribution of specific opioid receptor subtypes to this effect has yielded conflicting results. Some of these studies have shown that the effect is contingent upon the action of μ receptors while others have suggested that δ receptors are primarily responsible. The data reported here re-examine this question using the alcohol-preferring C57BL/6 mice. The results of this experiment demonstrate that d-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH 2 (CTOP), a μ-selective antagonist, and naltrindole, a δ-selective antagonist, are equally effective at reducing alcohol consumption in a limited access model compared to a saline control group. While there was no specific comparison of the effects of these drugs on alternative appetitive behavior, neither of these drugs had effects on measured off-session food or water consumption. The results of this experiment suggest that alcohol consumption is mediated by both μ- and δ-opioid receptor subtypes.

Effect of the combination of naltrexone and acamprosate on alcohol intake in mice.

Abstract  Both naltrexone and acamprosate have been utilized clinically in recovering alcoholics with varying success. In the experiment reported here the combination of naltrexone and acamprosate was examined in a limited access alcohol model using C57BL/6 mice to determine if there was evidence of additive or synergistic effects. The results of this experiment demonstrate that naltrexone, at the higher dose but not the lower dose, significantly reduced alcohol consumption. When combined with naltrexone, acamprosate reduced alcohol consumption across both doses of naltrexone. This effect was sensitive to both dose and number of days of exposure to the naltrexone/acamprosate combination.

Preliminary field trial of a putative research algorithm for diagnosing ICD‐11 personality disorders in psychiatric patients: 2. Proposed trait domains

This field trial examines the discriminant validity of five trait domains of the originally proposed research algorithm for diagnosing International Classification of Diseases (ICD)-11 personality disorders. This trial was carried out in South Korea where a total of 124 patients with personality disorder participated in the study. Participants were assessed using originally proposed monothetic trait domains of asocial-schizoid, antisocial-dissocial, anxious-dependent, emotionally unstable and anankastic-obsessional groups of the research algorithm in ICD-11. Their assessments were compared to those from the Personality Assessment Schedule interview, and the five-factor model (FFM). A total of 48.4% of patients were found to have pathology in two or more domains. In the discriminant analysis, 64.2% of the grouped cases of the originally proposed ICD-11 domains were correctly classified by the five domain categories using the Personality Assessment Schedule, with the highest accuracy in the anankastic-obsessional domain and the lowest accuracy in the emotionally unstable domain. In comparison, the asocial-schizoid, anxious-dependent and the emotionally unstable domains were moderately correlated with the FFM, whereas the anankastic-obsessional or antisocial-dissocial domains were not significantly correlated with the FFM. In this field trial, we demonstrated the limited discriminant and the convergent validities of the originally proposed trait domains of the research algorithm for diagnosing ICD-11 personality disorder. The results suggest that the anankastic, asocial and dissocial domains show good discrimination, whereas the anxious-dependent and emotionally unstable ones overlap too much and have been subsequently revised.

Effect of Zhubin (KI9) acupuncture in reducing alcohol craving in patients with alcohol dependence: A randomized placebo-controlled trial

ObjectiveTo examine the effect of acupuncture on Zhubin (KI9) in reducing alcohol craving in alcohol-dependent patients.MethodsTwenty male alcohol-dependent patients were randomly assigned to two groups, a treatment group (10 cases, age 43.0±6.8 years) and a placebo group (10 cases, age 44.5±7.9 years). The treatment group was treated with real needle acupuncture on Zhubin (KI9) twice a week for 4 weeks, and the control group was treated with placebo needle acupuncture. Both groups were given acupuncture treatment using Park Sham Device (PSD). Alcohol craving was measured by the Visual Analogue Scale (VAS) before treatment to establish a baseline, and after 1, 2, and 4 weeks of treatment. Repeated measures ANOVA was used to determine the main and interaction effects of time and on the outcome measure (VAS).ResultsThere was a significant effect of time on VAS score (df=3, F=13.3, P<0.01). Main effect of group on VAS score was significant (df=1, F=10.9, P<0.01) and the time×group interaction was also significant (df=3, F=4.7, P<0.01).ConclusionsReal-needle acupuncture therapy on Zhubin (KI9) showed effectiveness in reducing alcohol craving. These results strongly suggest the usefulness of acupuncture therapy on Zhubin (KI9) in preventing a relapse in alcohol dependent patients.

Schedule for personality assessment from notes and documents (SPAN-DOC): Preliminary validation, links to the ICD-11 classification of personality disorder, and use in eating disorders.

BACKGROUND The underlying core of personality is insufficiently assessed by any single instrument. This has led to the development of instruments adapted for written records in the assessment of personality disorder. AIMS To test the construct validity and inter-rater reliability of a new personality assessment method. METHOD This study (four parts) assessed the construct validity of the Schedule for Personality Assessment from Notes and Documents (SPAN-DOC), a dimensional assessment from clinical records. We examined inter-rater reliability using case vignettes (Part 1) and convergent validity in three ways: by comparison with NEO Five-Factor Inventory in 130 Korean patients (Part 2), with agreed ICD-11 personality severity levels in two populations (Part 3) and determining its use in assessing the personality status in 90 British patients with eating disorders (Part 4). RESULTS Internal consistency (alpha = .90) and inter-rater reliability (intraclass correlation coefficient ≥ .88) were satisfactory. Each factor in the five-factor model of personality was correlated with conceptually valid SPAN-DOC variables. The SPAN-DOC domain traits in those with eating disorders were categorized into 3 clusters: self-aggrandisement, emotionally unstable, and anxious/dependent. CONCLUSIONS This study provides preliminary support for the usefulness of SPAN-DOC in the assessment of personality disorder. Copyright

Acute Effects of Capsaicin on Proopioimelanocortin mRNA Levels in the Arcuate Nucleus of Sprague-Dawley Rats

Objective Capsaicin, a noxious stimulant and main component of the hot flavor of red peppers, has an analgesic effect when administered to humans. We investigated the expression of proopioimelanocortin (POMC) mRNA in the arcuate nucleus of Sprague-Dawley (SD) rats after administering capsaicin, hypothesizing that administering capsaicin activates the central opioid system. Methods SD rats were divided randomly into two groups; one group received a saline injection and the other received a capsaicin injection. The POMC mRNA level in the arcuate nucleus of the hypothalamus was measured by the reverse transcription-polymerase chain reaction at 0, 20, 40, 60, and 120 minutes after capsaicin administration. Results Capsaicin administration resulted in a significantly increased POMC mRNA level, compared to that in saline-treated rats at the 20-minute time point (t=-4.445, p=0.001). However, no significant group differences were observed at other times (t=-1.886, p=0.089; t= -0.973, p=0.353; t=-2.193, p=0.053 for 40, 60, and 120 minutes, respectively). Conclusion The analgesic effect of capsaicin might be associated with increased activity of the cerebral opioid system. This finding suggests that capsaicin acted for nociception and analgesia and could affect alcohol-intake behavior, which might further imply that a food culture could affect drinking behavior.

Open prospective study of ziprasidone in patients with schizophrenia with depressive symptoms: A multicenter study

The goal of this study was to examine the efficacy and safety of ziprasidone to treat depressive symptoms in Korean patients with schizophrenia who showed stable symptoms.

Effect of Feeding with High γ-Aminobutyric Acid (GABA) Containing Giant Embryo Black Sticky Rice (Oryza sativa L.) on Alcohol Intake in C57BL/6 Mice

It is known that black sticky rice with giant embryo (BSRGB, Milyang 263) and giant embryo rice (GER) contains higher levels of GABA than rice. Therefore, feeding BSRGB, GER, or rice freely to C57BL/6 mice with two-hour alcohol intake for 16 days was investigated. For two-hour alcohol intake, a repeated measure ANOVA (three treatment groups repeated across 16 days; 8 two-day blocks) yielded a significant group by block interaction (dfIt is known that black sticky rice with giant embryo (BSRGB, Milyang 263) and giant embryo rice (GER) contains higher levels of GABA than rice. Therefore, feeding BSRGB, GER, or rice freely to C57BL/6 mice with two-hour alcohol intake for 16 days was investigated. For two-hour alcohol intake, a repeated measure ANOVA (three treatment groups repeated across 16 days; 8 two-day blocks) yielded a significant group by block interaction (df=16, F=3.109, p=0.004). The independent t-test showed that significant suppression of two-hour alcohol intake was observed when subjects were administered with BSRGB, compared with the rice alone across all the two-day blocks (p<0.05). The paired t-test revealed that a significant suppression of two-hour alcohol intake was observed starting 4 to 16 days after freely feeding with BSRGB compared to before feeding. However, there is no significant difference in the two-hour alcohol intake observed between the before and after administration of rice. A repeated measure ANOVA revealed no significant group by block interaction for 22-hour water intake and body weight. However, a repeated measure ANOVA revealed a significant grouping by block interaction for food intake. These results indicate a change of two-hour alcohol intake is presumably caused by GABA, which is found in higher levels in BSRGB than in rice.

Calcium/calmodulin-dependent protein kinase IV gene polymorphisms in Korean alcohol-dependent patients

INTRODUCTION A relationship between alcohol dependence (AD) and calcium/calmodulin-dependent protein kinase IV (CAMKIV) has been reported in a whole genome study of Korean AD patients. The purpose of the present study is to compare the frequency of CAMKIV genotypes and alleles between AD and control subjects in Korea. METHODS The present study includes 281 AD patients and 139 control subjects. Seven single nucleotide polymorphism of CAMKIV gene known to show significant separation ratio in Asians were searched in SNP database and previous studies related to CAMKIV gene. Polymerase chain reaction and restriction fragment length polymorphism techniques were used to analyze genotype of CAMKIV gene SNPs. RESULTS Major TT genotype and T allele frequencies of rs 25917 in AD patients were significantly higher than those of control subjects (genotype frequency, p=0.002; allele frequency, p=0.001). Major CC genotype and C allele frequencies of rs 117590959 in AD patients were also significantly higher than those of control subjects (genotype frequency, p<0.001; allele frequency, p=0.001). Major genotypes of rs25917 (p=0.002, odd ratio: 3.13, 95% CI: 1.54-6.38) and rs11790959 (p=0.002, odd ratio: 3.22, 95% CI: 1.52-6.81) showed significantly higher odds ratios associated with AD than minor genotypes in logistic regression. DISCUSSION These results suggest that CAMKIV might be a candidate AD gene. Further research is needed to determine the precise relationship between CAMKIV and AD and the function of each SNP.