Dextromethorphan HBr의 남용과 중독증 3례

최인근,김경식 大韓神經精神醫學會 1983 신경정신의학 Vol.22 No.1

The authors experienced 3 cases of abuse and intoxication of abuse and intoxication of dextromethorphan HBr, nonnarcotic antitussive agents. A summary of the report is as follows: dextromethorphan HBr was supposed to be abused as an euphoriant. The abusers showed toxic symptoms which were similar to those of amphetamine of anticholinergic intoxication syndromes. The symptoms of the abuse and intoxication either disappeared spontaneously or were improved by chlorpromazine in 3 to 6 days.

마약과 환각제의 분류 및 약리학

崔仁根 대한의사협회 1998 대한의사협회지 Vol.41 No.4

측두하악 장애의 정신생리학적 측면에 대한 예비적 연구

손봉기,이정구,최인근 大韓神經精神醫學會 1991 신경정신의학 Vol.30 No.6

This study was designed to investigate the psychophysiologic aspects of temporomandibular disorder. Using various test batteries, 67subjects(33 of TMD patients and 34 of controls) were evaluated and the responses were analyzed through SPSS program. The results were as follows : 1) The score of social readjustment rating scale was significantly higher in the female patient group than in the female control group. 2) The patient group was less responsive to the pressure from financial difficulties, and the male patient group was less responsive to the changes in relationship and the pressure from financial difficulties than their respective control group. 3) Compared with the control group, the patient group was unfamiliar with the three coping strategies, namely shared concern, redefinition, and acting-out. Female patients were unfamiliar especially with the redefinition and acting-out, but very familiar with the compliance. 4) The patient group and the female patient group attained significantly higher score in Zung's self-rating depression scale than the control groups, respectively. 5) The scores of Hs. D, and Hy scales of MMPI of the patient group were significantly higher than those of the control group, and 1-3-2 type was most frequently noted in the patient group, though not significant.

한국어판 DIS-IV의 개발과 표준화

서국희,손현균,최상섭,이미경,이중서,최인근,방현숙,연병길 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.5

연구목적 : DSM-Ⅲ-R의 개정판이라기 보다는 새로운 진단 기준으로 간주될 정도였던 DSM-Ⅳ의 출현은 정신장애의 진단분류체계에 매우 큰 영향을 미쳤다. DSM-Ⅳ의 변화를 반영하여 정신과적 진단을 내릴 수 있도록 DIS-Ⅲ를 개정하여 DIS-Ⅳ가 개발되었다. 본 연구는 국내에서의 정신의학적 연구를 더욱 활성화하고 활발하게 국제 공동연구가 이루어질 수 있도록 DIS-Ⅳ 한국어판을 개발하고 이를 표준화하는 데 그 목적이 있다. 방 법 : 번역 위원회에서 번역, 역번역, 어의적 정확성 확인, 한국어 용법에 맞도록 수정한 후 예비 연구를 거쳐 한국어판 DIS-Ⅳ가 완성되었다. 의과대학생 4명에게 Washington University DIS-Ⅳ training course와 동일한 내용과 방법으로 교육을 실시하였다. 두 명의 조사요원들이 한 환자를 DIS-Ⅳ를 사용하여 동시에 검사한 후의 진단을 비교하여 검사자간 신뢰도를 측정하고, 정신과 의사가 독립적으로 DIS-Ⅳ를 사용하여 검사한 후의 진단과 비교하여 절차 타당도를 평가하였다. 조사 대상은 2000년 1월부터 8월까지 2개 대학 병원 정신과 및 국립감호정신병원에서 치료중이던 환자 124명이었다. 결 과 : 평가자간 신뢰도의 kappa값 평균은 0.74였다. 양극성 Ⅰ장애, 범불안장애, 우울장애, 강박장애, 반항장애, 동통장애, 병적 도박, 외상후 스트레스 장애, 특정공포증 및 대부분의 물질 사용 혹은 관련 장애의 kappa값이 0.7 이상이었다. 정신과 의사의 진단과 조사요원의 진단의 일치도를 비교한 절차 타당도를 살펴보면 다음과 같다. 전체적인 sensitivity는 67.6%, specificity는 98.3%, kappa 값은 0.69이었다. 물질 사용 장애 및 물질 관련 장애의 SE는 79%, SP는 98.6%, kappa 값은 0.77이었다. 이를 제외한 나머지 정신 장애의 SE는 60.5%, SP는 98%, kappa 값은 0.64이었다. 본연구의 결과는 Robins 등에 의해 최초로 보고된 DIS의 신뢰도 및 타당도와 거의 비슷한 수준이었다. 결 론: 한국어판 DIS-Ⅳ가 높은 신뢰도와 타당도를 지닌 것으로 생각된다. 이 도구를 통해 물질 사용 및 관련 장애를 타당도와 신뢰도 높게 진단할 수 있다는 점이 매우 중요하다. 향후 정신장애의 진단 능력을 향상시키고 임상연구를 활성화하고 국제적인 학술적 교류를 늘리는데 일조할 수 있을 것이다. Objective : Appearance of DSM-Ⅳ has influenced greatly on the nosological classification of mental disorder, not considered as revised one of DSM-Ⅲ-R but a new criteria. DIS-Ⅳ has been developed after revision of DIS-Ⅲ in consideration of various changes in DSM-Ⅳ. This study is to develop and validate the DIS-Ⅳ, Korean version to activate Korean psychiatric research much more and to modivate more frequent international collaborative study. Method : Translation committee produced DIS-Ⅳ, Korean version through all the procedures of translation, back-translation, confirmation of retained original meaning of the English version, adaptation to Korean linguistic usage and preliminary study. Four medical students were trained during DIS-Ⅳ training course that retained the same contents and methods as of Washington University. Inter-rater reliability was measured by comparison between two diagnoses made from two interviewer who rated one patient at the same time. Procedural validity was measured by comparison between lay-interviewer's diagnosis and psychiatrist's diagnosis which were made after independent DIS-Ⅳ using interview. Subjects were 124 patients who were being treated at two University Hospital and National Forensic Psychiatric Hospital between January, 2000 and August, 2000. Results : Average kappa value of inter-rater reliability was 0.74. Diagnoses showing over 0.7 in kappa value were bipolar I disorder, generalized anxiety disorder, depressive disorder, obsessive-compulsive disorder, oppositional defiant disorder, pain disorder, pathological gambling, post-traumatic stress disorder, specific phobia and almost all substance use disorder or substance-related disorder. Procedural validity, that compared lay-interviewer's diagnosis and psychiatrist's diagnosis, were as follows: For all diagnoses, sensitivity, specificity and kappa were 67.6%, 98.3% and 0.69. For diagnoses of substance use disorder or substance- related disorder, sensitivity, specificity and kappa were 79%, 98% and 0.77. For other diagnoses except substance use disorder or substance- related disorder, sensitivity, specificity and kappa were 60.5%, 98% and 0.64. This results are almost at the same level as that of Robins and her colleagues who tirst reported reliability and validity of DIS. Conclusion : We think that DIS-Ⅳ, Korean version has higher reliability and validity. It is very important that diagnoses of substance use disorder and substance-related disorder can be made reliably and validly by this instrument. We expect that it can help to improve diagnosability of mental disorder, activate clinical research and increase international scientific communication.

정신분열병과 N-Methyl-D-Aspartate 수용체 유전자와 연관된 VNTR 표지자인 D9S158 다형성의 연합

김종원,채영규,정은기,김길숙,박강규,이영호,최인근,양병환,한진희 大韓神經精神醫學會 1998 신경정신의학 Vol.37 No.5

정신분열병과 NMDA 수용체와 연관된 D9S158 유전적 표지자와의 연관성을 알아보기 위해 75명의 정신분열병 환자군과 87명의 정상대조군을 대상으로 중합효소연쇄반응을 이용하여 연합연구를 시행하여 다음과 같은 결론을 얻었다. D9S158 유전좌위에는 모두 8개의 대립유전자가 있었고, 각 대립유전자는 cytosine-adenine염기가 반복되는 217염기쌍에서 233염기쌍의 형태였다. 먼저 정신분열병 환자와 정상대조군의 대립유전자의 빈도를 비교해 본 결과 통계적으로 유의한 차이를 보이지 않았다(p〉.05). 환자군을 좀 더 동질적으로 만들기 위해 정신분열병의 가족력 유무, 음성 및 양성증상, 연성신경학적 징후, DSM-IV 임상아형에 따라 환자군을 나누어 대립유전자의 빈도를 비교해 본 결과, 특정 임상양상과 관련이 있는 대립유전자를 발견하지 못하였다. 결론적으로 본 연구에서는 D9S158 유전좌위와 정신분열병의 연관성을 입증하지 못하였으나 NMDA 수용체 유전자주위의 다른 표지자나 좀 더 유전적으로 동질한 환자군을 대상으로 한 추후연구가 필요할 것으로 생각된다. An association study with Korean schizophrenic patients(N=75) and normal controls(N=87) was performed to find the relationship between D9S158 polymorphism and schizophrenia using polymerase chain reaction. Eight different alleles of a dinucleotide polymorphism on D9S158 locus were observed in both group. When we compared the frequencies of alleles between schizophrenics and normal controls, there was no significant difference between two groups. To increase homogeneity of schizophrenic group, we divided schizophrenic group by clinical phenotypes such as family history, negative and positive symptoms(PANSS), soft neurologic signs(NES-K) and DSM-IV diagnostic subtypes. Then we compared the frequencies of alleles among subgroups of clinical phenotypes, and there were no significant differences between subgroups(p〉.05). Although our findings fail to provide an evidence of association between schizophrenia and D9S158 locus, further investigation of other loci that are linked to NMDA receptor gene may be needed in genetically homogeneous subgroups of schizophrenia.

24주간 추적하는 임상 연구에서 한국인 남자 알코올 의존 환자의 비재발률

강철중,김성곤,남궁기,조동환,이병욱,최인근,최용성,박성봉,제영묘,김현경,김성연 大韓神經精神醫學會 2006 신경정신의학 Vol.45 No.1

Objetives : In order to provide useful data tbr the further clinical studies with Korean alcohol-dependent patients, enrollment and non-relapse rates were investigated while alcohol-dependent patients wcre followed up for 24 weeks. Methods : The subjects of this study were alcohol-dependent male patients who, for the first time, visited a hospital among 3 groups of hospitals, University Hospital, General Hospital or Mental Hospital, or those who needed to be followed up after discharge from those hospitals. After assigning 12 subjects to each hospital, we investigated enrollment and non-relapse rates while cognitive-behavioral therapy and pharmacotherapy were provided. Results : 1) Forty-eight patients were enrolled and the rate of enrollment was 36.4%. The enrollment rate in the University Hospital group was 52.1%, in the General Hospital group 50.0%. and in the Mental Hospital group 10.4%. 2) In 48 patients, non-relapse rate was 27.1% at 12 week and 18.8% at 24 weeks after starting follow-up. It was 24.4% and 20.0% at 12 and 24 weeks, repectively, in the University Hospital group while the General Hospital group showed 33.3% and 16.7%, respectively, and the Mental Hospital Group showed 20.0% at both 12 and 24 weeks. Conclusion : These results provide important data for further clinical studies of Korean alcohol-dependent patients.

정신분열병과 Neurotensin 수용체 유전자 다형성의 연합 연구

이유상,김형배,한진희,채영규,이정식,이혜순,주연호,김형섭,최인근,양병환 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.6

연구목적: Neurotensin(NT)은 NT수용체와 결합하여 그 효과를 나타내는 neuromodulator 혹은 neurotransmitter로서 대뇌에서 도파민의 분비를 조절하는데 중요한 역할을 한다. 근래의 연구에 의하면 NT와 그 수용체는 대뇌에서 항정신병 약물의 효과를 매개하는 것으로 생각되고 있으며 약물치료를 받지 않은 정신분열병 환자의 뇌척수액에서 NT의 양이 적으로 보고되고 있어 이들은 정신분열병과 깊은 관련을 가지고 있을 것으로 추정된다. 최근 NT수용체의 유전자의 3`인접영역에서 정보가치가 높은 4 염기반복 다형성이 발견되어 이를 유전 표지자로 하여 정신분열병과의 연합을 알아보았다. 방 법: 서로 혈연관계에 있지 않은 정신분열병 환자 120명(남자 91명, 여자 29명)과 정상 대조군 106명(남자 84명, 여자 22명)을 대상으로 하였다. PANSS를 사용하여 양성 및 음성을 알아보았다. 말초혈액에서 DNA를 분리한 후에 중합효소연쇄반응을 사용하여 3`인접영역에 있는 4 염기 반복 다형성을 증폭하였고 silver staining한 후에 유전자형을 관찰하였다. chi-square 검증과 Bonferroni`s correction을 사용하여 환자군과 정상 대조군간의 대립유전자 빈도의 차이를 알아보았다. 또한 양성 및 음성 환자군으로 나누어 차이를 알아보았다. 결 과: 총 23개의 대립유전자가 관찰되었으며, 399bp의 대립유전자(A10)의 빈도가 환자군보다 정상대조군에서 통계적으로 유의하게 높았다(χ²=16.49, df=1, p<0.001). 음성 정신분열병 환자군과 정상대조군 사이의 비교에서는 정상대조군의 A10의 빈도가 환자군보다 유의하게 높았다(χ²=21.33, df=1, p<0.001). 성별 비교에서 남자 정신분열병 환자군은 대조군에 비하여 A10의 분포가 유의하게 적었다. (χ²=13.71, df=1, p<0.001) 결 론: NT 수용체 유전자와 정신분열병사이에 음성연합이 관찰되었다. NT 수용체 유전자가 일부 정신분열병의 발병과정에서 확실하지는 않지만 어떤 종류의 보호기능을 할 수도 있다는 것을 암시한다. Objectives: Neurotensin(NT), of which functions are evoked by its interaction with neurotensin receptors(NTR), coexists with mesolimbic dopamine and regulates endogenous dopamine release. Recent studies have shown that NT with NTR exerts neuroleptic-like activity within the central nervous system and may play an important role in the pathogenesis and in the treatment of schizophrenia. We have examined the gentic association between schizophrenia and tetranucleotide repeat polymorphism in the 3-flanking region of the NTR gene to investigate the possible contribution of the NTR gene to the schizophrenia susceptibility. Methods: Among 23 alleles identified, the subjects were 120 patients(male 91, female 29)with schizophrenia and 106 normal healthy controls(male 84, female 22). They were unrelated native Korean. PANSS was used to determine positive or negative subgroup in the schizophrenic patients. Using polymerase chain reaction and polyacrylamide gel electrophoresis, tetranucleotide repeat polymorphism(CCTT and CTT) in the 3`-flanking region of NTR gene was observed. For a comparison of NTR gene`s allelic frequencies between patients with schizophrenia and normal healthy controls, chi-square test and Bonferroni`s correction was performed. Results: The frequency of A10 allele(base pair size=399)was significantly higher in normal healthy controls than schizophrenia(χ²=16.4902, df=1, p<.000). In the comparison between schizophrenic patients with negative symptoms and normal controls, the frequency of A10 allele was significantly higher in normal healthy control subjects than patients with schizophrenia(χ²=21.33, df=1, p<0.001). In the case of male, the frequency of A10 allele of schizophrenia was significantly higher than normal controls(χ²=13.71, df=1, p<0.001). Conclusions: NTR gene was negatively associated with schizophrenia. NTR gene`s tetranucleotide repeat polymorphism may provide some protective function against schizophrenia.

Scanning of genetic effects of alcohol metabolism gene (ADH1B and ADH1C) polymorphisms on the risk of alcoholism

Choi, Ihn-Geun,Son, Hyun-Gyun,Yang, Byung-Hwan,Kim, Seok Hyeon,Lee, Jun-Suk,Chai, Young-Gyu,Son, Bong Ki,Kee, Baik Seok,Park, Byung Lae,Kim, Lyoung Hyo,Choi, Yoo Hyun,Shin, Hyoung Doo Wiley Subscription Services, Inc., A Wiley Company 2005 Human mutation Vol.26 No.3

<P>Alcoholism is a multifactorial and polygenic disorder involving complex gene-to-gene and gene-to-environment interactions. Alcohol metabolism is one of the biological determinants that could significantly be influenced by genetic polymorphisms in alcohol-metabolism genes. These genetic polymorphisms are believed to influence drinking behavior and development of alcoholism. Direct DNA sequencing of whole ADH1B and ADH1C genes revealed 36 sequence variants, including six nonsynonymous and 14 novel polymorphisms. Seventeen polymorphisms among them were selected for genotyping in a larger study (n=352) based on linkage disequilibria (LDs) among SNPs, locations, and frequencies. Hardy-Weinberg equilibrium (HWE) analyses of polymorphisms revealed severe deviations only in alcoholics, which strongly suggest that a selection bias (or pressure) may be involved. The analyses of genotype distribution in alcoholics (n=106) and normal controls (n=246) showed dramatic associations with the risk of alcoholism. Fourteen polymorphisms in ADH1C and ADH1B showed a series of different strengths of association and magnitudes of risk. Based on referent and subgroup analysis, it was strongly suggested that the genetic effects come from the ADH1B*47Arg/*47Arg genotype, and that the positive signals from other sites are just tracking the genetic effect of ADH1B His47Arg. In this article we present summaries of previous studies and of the present study, to give an overview of the worldwide effects of ADH1B His47Arg on the risk of alcoholism. The information derived from this study could be valuable for understanding the genetic factors involved in the risk of alcoholism and facilitate further investigation in other ethnic groups. Hum Mutat 26(3), 224–234, 2005. © 2005 Wiley-Liss, Inc.</P>

알코올리즘의 약물 치료:

최인근(Ihn-Geun Choi) 한국중독정신의학회 1998 중독정신의학 Vol.2 No.2

GABA (γ-aminobutyric acid) is the most important inhibitory neurotransmitter in central nervous system. The toxic, amnesic and ataxic effects of alcohol are related with GABAergic activity. The GABAergic drugs being used for alcoholism can 1) block different manifestations of ethanol intoxication, 2) affect alcohol craving or 3) alleviate different signs of physical dependence. RO15-4513, a partial inverse agonist binding to the (GABA)A-receptor regulated chloride channel, antagonizes the effects of ethanol on the channel, and reverses ethanol-induced intoxication. Calcium acetylhomotaurinate(acamprosate), structurally related to glutamate and GABA, decreases ethanol ingestion and relapse rate in ethanol dependent individuals. Drugs enhancing GABAergic activity can be used for adequate inhibition of alcohol withdrawal syndrome. Gamma-vinyl-GABA (vigabatrin, GABA-transaminase inhibitor) could have a potential role in the treatment of alcoholism and in some of the problems of ethanol withdrawal. Benzodiazepines are the treatment of choice in alcohol withdrawal. Sufficient dosage of benzodiazepine should be used for improving alcohol withdrawal symptoms on the first day of treatment.

알코올 의존 환자에서 혈청 아질산염 농도와 일부 생물학적 지표와의 관련성

최인근(Ihn-Geun Choi),신형직(Hyong-Jik Shin),송동근(Dong-Keun Song),고재광(Jae-Kwang Koh),김상국(Sang-Kook Kim),손현균Hyun-Gyun Son),서국희(Guk-Hee Suh) 한국중독정신의학회 2003 중독정신의학 Vol.7 No.2

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 the alcohol-induced brain damage. The purpose of this study was to determine the difference between alcohol dependence group and healthy control group in concentration of the nitrite, a stable metabolite of NO, and it’s relationship to clinical and biochemical markers of alcohol dependence. Methods:Thirty-four subjects diagnosed as alcohol dependence according to DSM-IV diagnostic criteria were evaluated for the clinical characteristics and biochemical markers of alcohol dependence when their CIWA-Ar scores had reached zero after the alcohol withdrawal treatment with benzodiazepine. Thirtyfour healthy controls were also evaluated. Clinical characteristics were evaluated by CAGE and AUDIT questionnaire. 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 alcoholics were not different from those in the controls. 2) There were no significant associations between the nitrite concentration and the clinical and biological markers of alcohol dependence. 3) There was a negative correlation between the nitrite concentration and the days after last drink. Conclusion:These findings suggest that NO may be neither a causative agent nor trait marker of alcohol dependence. Rather, NO may be a state marker of recent alcohol drinking and alcohol withdrawal.