• Korean Journal of Biological Psychiatry
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• v.13 no.3
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• pp.178-190
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• 2006

Objectives : We investigated the relationship of the alcohol withdrawal symptoms with genetic polymorphism among alcohol dependence patients. Method : The measuring instruments used in this study were the Clinical Institute Withdrawal Assessment for Alcohol(CIWA-Ar). We analyzed DRD2 TaqI A polymorphism, dopamine transporter(DAT 1) polymorphism, and catechol-O-methyltransferase(COMT) polymorphism in 108 male alcoholics and 76 healthy controls. Results : The major findings was as follows. No significant differences for genotype distribution or allele frequency were revealed comparing controls and alcoholic patients. DRD2 Taq I : The subscale score of auditory hallucination among CIWA-Ar scale in homozygote was significantly higher than in heterozygote(OR=1.34). The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. DAT1 : In the subject without DAT-9 gene allele, it was significantly higher of the subscale score of sweating, anxiety among CIWA-Ar scale than in the subject with DAT-9 gene allele. And The total score of CIWA-Ar scale in the subject without DAT-9 gene allele was significantly higher than in the subject with DAT-9 gene allele. COMT : The total score of CIWA-Ar scale in heterozygote was significantly higher than in homozygote. Conclusion : Our results suggest the relationship between specific genetic factors and the withdrawal symptoms of alcohol dependent patients. As the candidate gene of the severity of alcohol withdrawal syndrome, DRD2 Taq1 gene was recommended.

• Korean Journal of Biological Psychiatry
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• v.11 no.1
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• pp.33-39
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• 2004

Objective:Nitric oxide(NO) has been known to be associated with tolerance and preference to alcohol. It has also been known to affect various alcohol drinking behavior, alcohol withdrawal symptoms and alcohol- induced brain damage. The purpose of this study was to determine the difference, among alcohol dependence group, alcohol drinking group and abstinence group, in serum concentration of nitrite, a stable metabolite of NO, and it's relationship to clinical and biochemical markers of alcoholism. Methods:Forty subjects diagnosed as alcohol dependence according to DSM-IV diagnostic criteria were evaluated for the clinical characteristics and biochemical markers of alcohol dependence including nitrite with their CIWA-Ar scores checked just after admission. Thirty-nine healthy controls were also evaluated, divided into twenty-three alcohol drinking group and sixteen abstinence group. Clinical characteristics were evaluated by CIWA-Ar, CAGE and AUDIT questionnaires. Aspartate aminotransferase(AST), alanine aminotransferase (ALT), gamma glutamyltransferase(GGT) and mean corpuscular volume(MCV) were used as the biochemical markers of alcohol dependence. Serum nitrite concentrations were measured by Griess reaction. Results:1) The concentrations of nitrite in alcohol dependence patients were not different from those in the control subjects. 2) There were no significant association between the nitrite concentrations and the CIWA-Ar scores in alcohol dependence patients. 3) Nitrites are significantly increased in alcohol dependence group and alcohol drinking group compared with abstinence group. Conclusions:These findings suggest that serum nitrite concentration has no relation with alcohol withdrawal symptoms, but alcohol drinking increases serum nitrite concentration influenced by general condition of the body.

• Korean Journal of Psychosomatic Medicine
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• v.11 no.2
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• pp.196-204
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• 2003

Objectives: It is known that sedative hypnotics would make cross tolerance with alcohol and deteriorate quality of sleep in alcoholics. Light therapy is effective non-pharmacological intervention for sleep disturbance in circadian phase disorders, jet-lag, shift-work and age-related sleep disorders. Authors would investigate the effects of morning light therapy on sleep of patients with alcohol dependence during recovery state without withdrawal symptoms. Methods: 13 patients with alcohol dependence who have not any alcohol withdrawal symptom were recruited. Light therapy during 1 hour in the morning had been administered by 2500 Lux light box through serial 3 days. Sleep state of subjects were assessed by sleep log and the subjective satisfaction at sleep was by 100 mm visual analogue scale. Sleepiness, depressive mood, anxiety were evaluated by 100mm visual analogue scale at 8 AM, 2 PM and 8 PM. For assessment of performance ability that would be associated with sleepiness and vigilance, trail making test A, B and digit symbol substitution test were performed by two times on base line and 4th day. Univariate repeated-measures ANOVAs were performed for each measures except performance tests which were analysed by paired t-test. Results: Sleep latency and sleep efficiency were significantly improved with light therapy and satisfaction at sleep was. There was no significant difference in sleepiness at 2 PM with light therapy but sleepiness at 8 AM significantly decreased and at 8 PM increased. The time to complete Trail making test and digit symbol substitution test were significantly shortened at 4th day compared with baseline. Fatigue at 8 AM were not significantly changed with light therapy but at 2 PM and 8 PM significantly decreased. Depressive mood and anxiety were not significantly changed with light therapy. Conclusion: Although this study had some limitations, it showed that light therapy would be effective modality on sleep disturbance of patients with alcohol dependence who have recovered from alcohol withdrawal symptoms. It is proposed that short term light therapy could be used clinically for alcoholics with insomnia. In the future, long term controlled studies using more objective tools for sleep are required to further investigate the effect of light therapy in alcoholics.

• Journal of Life Science
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• v.19 no.4
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• pp.532-537
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• 2009

Previous studies reported that the N-methyl-D-aspartate (NMDA) receptor is related to alcohol dependence in terms of developing withdrawal or tolerance, however, it is controversial whether NMDA receptor antagonists are effective in preventing relapse in alcohol-dependent patients or not. The purpose of this study was to investigate the effect of memantine, an NMDA receptor antagonist, on alcohol intake in C57BL/6 mice, which prefer drinking hereditarily. Using limited access procedures in C57BL/6 mice in the state of alcohol dependence, vehicle, naltrexone 1.0 mg/kg or, memantine 5, 25, or 50 mg/kg i.p. was administered respectively for twelve days. Medication effects on 2-hours alcohol, 22-hour water, and 24-hour food intake and body weight were studied. Using repeated measure ANOVA, the naltrexone 1 mg/kg, memantine 5, 25, or 50 mg/kg, and vehicle groups showed significant medication by day interaction (naltrexone, df=4, F=11.827, p<0.01, memantine 5 mg/kg, df=4, F=7.999, p<0.01; memantine 25 mg/kg, df=4, F=6.199, p<0.05; memantine 50 mg/kg, df=4, F=10.522, p<0.01) in 2-hour alcohol intake. In 3 memantine groups, there was no significant medication by day interaction with the vehicle group in 22-hour water intake, 24-hour food intake, or body weight. The naltrexone and vehicle groups showed significant medication by day interaction in body weight, but not in 22-hour water or 24-hour food intake. From these results, it is suggested that memantine treatment can affect alcohol intake in mice. Therefore, it is possible that a pure NMDA receptor antagonist is effective in preventing relapse in alcohol-dependent patients.

• Korean Journal of Biological Psychiatry
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• v.6 no.2
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• pp.219-226
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• 1999

Objectives : The aims of this study were to evaluate changes in plasma superoxide dismutase(SOD) activities in alcohol depedence, to find out variables to influence on the SOD activities, and finally to identify the correlation of SOD activities with the alcohol-associated cognitive disorders. Methods : For 24 male alcoholics and 21 healthy male controls, plasma SOD activities were measured by spectrophotometry on 1-2 wks after alcohol withdrawal. Structured interviews and laboratory tests were also performed. Results : 1) Upon comparing SOD activities between controls and alcoholics, the SOD activities were significantly(p<0.01) lower in alcoholics($0.308{\pm}0.140$ units/mL) than in healthy controls($0.313{\pm}0.086$ units/mL). 2) Upon comparing SOD activities according to the presence of alcohol-related cognitive disorders, the SOD activities were significantly(p<0.05) lower in alcoholics with cognitive disorders($0.247{\pm}0.049$ units/mL) than in alcoholics without cognitive disorders($0.317{\pm}0.148$ units/mL). 3) Upon comparing SOD activities according to the presence of alcoholic polyneuropathy or alcohol withdrawal seizure, the SOD activities showed no significant differences between alcoholics with polyneuropathy or epilepsy and those without. 4) Upon analyzing variables influencing on the SOD activities in alcoholics, the SOD activities had the negative correlation with hemoglobin(${\gamma}=-0.433$) and severity of alcohol withdrawal symptoms(${\gamma}=-0.375$). 5) Upon comparing variables according to the presence of alcohol-related cognitive disorders, the occurrence of alcoholic polyneuropathy(p<0.05) and blood phosphorus concentrations(p<0.01) were significantly higher in alcoholics with cognitive disorders than those without. 6) Upon analyzing an association between SOD activities and variables in alcoholics with cognitive disorders, the SOD activities were positively correlated with the onset age(${\gamma}=0.995$), and negatively correlated with the severity of alcohol withdrawal symptoms(${\gamma}=-0.996$). Conclusions : Lower SOD activities in alcohol dependence suggested alcohol-associated cognitive disorders and alcohol withdrawal symptoms might be caused by oxidative stress.

• Korean Journal of Biological Psychiatry
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• v.5 no.1
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• pp.34-45
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• 1998

We provide the reader with a brief introduction to the neurobiology of neuropeptides. Several comprehensive reviews of the distribution and neurochemical, neurophysiological, neuropharmacological and behavioral effects of the major neuropeptides have recently appeared. In reviews of the large number of neuropeptides in brain and their occurance in brain regions thought to be involved in the pathogenesis of major psychiatric disorders, investigators have sought to determine whether alternations in neuropeptide systems are associated with schizophrenia, mood disorders, anxiety disorders, alcoholism and neurodegenerative disease. There is no longer any doubt that neuropeptide-containing neurons are altered in several neuropsychiatric disorders. One of the factors that has hindered neuropeptide research to a considerable extent is the lack of pharmacological agents that specifically alter the synaptic availability of neuropeptides. With the exception of naloxone and naltrexone, the opiate-receptor antagonists, there are few available neuropeptide- receptor antagonists. Two independent classes of neuropeptide-receptor antagonists has been expected to be clinically useful. Naltrexone, a potent ${\mu}$-receptor antagonist, has been used successfully to reduce the need for alcohol consumption. And cholecycstokinin antagonists are now in development as a new class of anxiolytics, which would be expected to be free from tolerance and physical dependence and lack of sedation. In this review, we deal with these two kinds of neuropeptide system, the opioid system and cholesystokinins in the brain. The role of opioid systems in the reinforcement after alcohol consumtion and that of cholesystokinins in the pathogenesis of anxiety will be discussed briefly. As we know, the future for neuropeptides in psychiatry remains bright indeed.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.1
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• pp.33-38
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• 2007

Recently, the lifetime prevalence rate of alcoholism in Korea shows to be quite higher than that in American, European and Asian countries indicating approximately 11 %. Also prevalence rate of male adult alcoholism in total inpatient of a polyclinic hospital shows to be very high indicating 16.5 % to 38.2 %, and from this result it is could be supposed that considerable physical diseases are related with alcoholic problem. According to the disorder related with alcohol is one of the most important hygienic problems in our society. In spite of the development of medicine, there is no certain medication or method in the field of the adult diseases or cancers under the actual circumstances that foods and drugs have been taking approximately for the purpose of prevention; and from this viewpoint, functional foods proved to be physically effective compared to general foods have been developing and the natural substances that could increase the effectiveness of general food have been produced. Alcohol addiction has been inducing several social problems and according to the increasing trend following the development of society it is strongly required to develop the medication. Therefore the research regarding to the treatment for the alcohol addiction has been performed widely, and especially the attempt to developof new medication using herbal medicine has been performing as in the development of the medication for other diseases. This study was designed to investigate the effect of Glycyrrhizae Radix which is the representative herbal medicine and has been used widely in the preparation of herbal medicine on alcohol intake and alcohol withdrawal syndrome.

• Korean Journal of Psychosomatic Medicine
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• v.16 no.2
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• pp.69-74
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• 2008

Delirium is an organic psychiatric syndrome characterized by an acute onset, prominent disturbance of consciousness and cognitive impairment with fluctuating course. Although there is not a clear consensus concerning the optimal classification system for delirium subtypes, Lipowski(1983) firstly classified delirium by psychomotor activity, namely hyperactive, hypoactive, and mixed. According results of several following studies, prevalence of hypoactive delirium were not less than that of hyperactive delirium. But a diagnosis of hypoactive delirium often missed, which is most frequently misdiagnosed as depression and dementia. Hyperactive delirium can be caused by alcohol or benzodiazepine withdrawal, would be related with excessive dopamine and cholinergic deficiency, and is more responsive to high-potency antipsychotics therapy. Hypoactive delirium would be caused by metabolic encephalopathy, and tends to present a less responsiveness to antipsychotics and poorer overall prognosis with a prolonged duration of admission than hyperactive delirium. Delirium is not a homogenous syndrome. Because of different subtypes, it may have dissimilar underlying pathogenetic pathways. So different treatment strategies between various subtypes may be needed.

• Journal of Trauma and Injury
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• v.21 no.2
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• pp.115-119
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• 2008

Purpose: Abrupt abstinence from alcohol in cause of chronic alcohol addiction can trigger alcohol withdrawal syndrome. The authors studied the effect of post-operative alcohol withdrawal syndrome in patients who require intensive care due to trauma. Methods: For the study group, we selected 70 patients who had undergone emergency surgery from May 2003 to March 2007 due to trauma and who had been treated with prophylactic thiamine. Data was collected retrospectively. We excluded those who extended their hospital stay for other than traumatic causes, those who died within 3 days of surgery after trauma, those who transferred to other institutions, and those who received a psychiatric diagnosis. Patient groups were determined by the existence or the non-existence of withdrawal syndrome. Age, sex, injury mechanism, mortality, complications, durations of hospital stay and intensive care, use of mechanical ventilator, and sedative use were investigated. A Chi-square test and The Mann-Whitney method were used for statistical analysis in this study. Results: Twenty-four (24) patients from the 58 who had an ISS of 16 or more showed alcohol withdrawal syndrome, and men were shown to be affected with the syndrome significantly more than women. Although ISS was higher in the group with alcohol withdrawal syndrome, statistically, the difference was not significant (P<0.08). The total hospital stay in the patient group with alcohol withdrawal syndrome was on average 10 days longer. However, the difference was not significant (P<0.054). The duration of intensive care in the patient group with alcohol withdrawal syndrome was significantly longer (P<0.029). The patients with alcohol withdrawal syndrome showed no significant difference in the duration of mechanical ventilator use (P<0.783), or in the duration of sedative use (P<0.284). Respiratory distress, pneumonia, upper airway infection, sepsis, acute renal failure, and mortality in the alcohol withdrawal syndrome group were investigated, but no statistically significant difference were noted. Conclusion: We found that the duration of intensive care in chronic alcohol abusers was longer due to the development of alcohol withdrawal syndrome. We also discovered that, when the patients overcame the symptoms of alcohol withdrawal syndrome after intensive care, no difference was found in the frequency of developing complications, the morbidity, and the mortality. Therefore, we conclude that intensive care in trauma patients who are chronic alcohol abusers decreases the incidence of complications found in patients with post-operative alcohol withdrawal syndrome and does not adversely impact the prognoses for those patients.