알코올 의존과 파킨슨병 병태생리에서의 살소리놀(Salsolinol)

정인원,정성훈,김진영 大韓神經精神醫學會 2008 신경정신의학 Vol.47 No.3

Salsolinol, a dopamine-derived tetrahydroisoquinoline, is one of the endogenous alkaloids structurally related to morphine. It has been implicated in the pathophysiology of alcohol dependence and Parkinson's disease since it’s first discovery in 1970’s. Salsolinol is involved in many neurophysiological processes, including modulation of dopamine activity, facilitation of prolactin release and reinforcement of additive substance craving. In addition, salsolinol exerts highly neurotoxic effects on dopaminergic neurons ultimately leading to apoptosis, which is mediated by inhibition of endogenous antioxidants and, thereby, production of reactive oxygen species (ROS). These properties are considerably based in alcohol dependence and several neurodegenerative disorders including Parkinson's disease. Salsolinol is synthesized by the condensation of dopamine with acetaldehyde or Pyruvate through enzymatic or non-enzymatic processes in the dopamine-rich neurons. Acute alcohol ingestion increase the level of acetaldehyde and salsolinol is structurally related to endogenous opioids. Therefore, it has been suggested that salsolinol may be the missing link between alcohol ingestion and the activation of reward pathway in the mesolimbic brain. The reinforcing effect of both alcohol and salsolinol in self-administration setting also strongly supports this hypothesis. N-methylsalsolinol, the major metabolite of salsolinol, is highly neurotoxic and responsible for the selective destruction of dopaminergic neurons in Parkinson's disease. In contrast to this, several structural analogs of salsolinol act as endogenous anti-parkinsonism substances. Delicate Structural differences may underlie this peculiar properties. It may become possible to introduce fine structural modifications, even stereo-specific manipulations, to develop entirely newer kinds of antiparkinsonism drugs. Although the implication of salsolinol in the pathophysiology of alcohol dependence had been suggested long ago, the progression of the related research was at most very limited up to now. Even now, this important chemical, deeply involved in a wide range of essential neurophysiological processes, still is relatively neglected by psychiatric researchers. However, it is expected that the accumulating knowledge of salsolinol's neuromodulatory and neurotoxic effects will give new insights into the many dopamine related psychiatric disorders including substance dependence, parkinsonism and schizophrenia. We expect that many psychiatrists will give proper attention to this highly promising research subject.

위 유문동 평활근 세포에서 Caffeine에 의해 활성화되는 이온 전류에 관한 연구

정인원,이무열,방효원,엄대용,이상돈 중앙대학교 의과대학 의과학연구소 1992 中央醫大誌 Vol.17 No.3

In order to clarify the existence of the non-selective cationic channel of CI^- -channel in gastric antral smooth muscle cells which suggested to play a critical role in generation and maintenance of depolarization and exitability, the whole cell mode of patch-clamp experiment was conducted. Following results were obtained ; 1. Puff injection of caffeine induced the increase of inward currents in the hyperpolarized holding potential ranges, and the increase of outward currents in the hypopolarized range. 2. In the case of blocking of all known currents, these current components were observed. 3. These current components were disappeared when known as a Cl^- -channel blocking agent was treated and intracellular EGTA concentration was increased. The above results could be concluded that these current components strongly suggested as a Ca^2+ -dependent Cl^- current in the gastric antral smooth muscle cells.

정신보건센터의 주간 및 직업재활 프로그램에 등록한 정신분열병 환자의 연령군간 특성

정인원,김헌,손정우,이선영,김혜영,서동우 大韓神經精神醫學會 2004 신경정신의학 Vol.43 No.1

항정신병약물이 정신분열병 증상에 미치는 영향 : 리스페리돈과 할로페리돌의 임상적 효과 비교

정인원 충북대학교 의과대학 충북대학교 의학연구소 1999 忠北醫大學術誌 Vol.9 No.2

연구목적: 비정형 항정신병약물과 정형 항정신병약물을 비교하기 위해서 risperidone과 haloperidol의 임상효과와 부작용에 대한 후향성 개방 연구를 수행하였다. 대상 및 방법: 20명의 정신분열병환자를 대상으로 나이와 성별을 일치시켜 두 치료집단을 나누어 4주간 정신 증상을 측정하였다. 환자의 정신 증상은 정신분열병의 양성 음성 증후군 척도(PANSS), 단기 정신증 척도(BPRS), 해밀턴 우울 척도(HAMD), 해밀턴 불안 척도(HAMA), 전반적 공격성 척도(OAS), 예일-브라운 강박 척도(YBOCS)등을 사용하였다. 약물의 부작용은 추체외로 증상 평가 척도(ESRS)와 비정상적 불수의 운동 척도(AIMS)로 측정하였다. 결과: 두 치료 집단 모두에서 임상 증상의 호전을 보였다. 그러나 집단간에 증상 호전의 차이는 보이지 않았다. 그 외 추체외로 증상 및 부작용도 차이를 보이지 않았다. 결론: 비정형성 항정신병약물인 risperidone은 정신분열병환자의 치료에서 적어도 4주간의 치료 초기에는 정형 항정신병약물인 haloperidol에 비하여 우월한 임상 효과를 보이지 않았다. Purpose: A retrospective open clinical study was conducted to evaluate the clinical efficacy and the side effect of atypical antipsychotics in comparison with conventional antipsychotics. Materials and Methods: Twenty schizophrenic patients were divided to two groups and assessed the psychopathology once a week for four weeks. The symptoms were assessed by means of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), the Brief Psychotic Rating Scale (BPRS), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A), the Overt Aggression Scale (OAS) and the Yale-Brown Obsessive Compulsive Scale (YBOCS). The side effects were assessed by the Extrapyramidal Symptom Rating Scale (ESRS) and the Abnormal Involuntary Movement Scale (AIMS). Results: The results indicated that two antipsychotics, risperidone and haloperidol showed improvements of clinical symptoms for four weeks of treatment. And any differences between two groups were not found. Conclusion: This study suggests that the superiority of risperidone over haloperidol is not apparent during the initial period of antipsychotic treatment.

알코올 의존과 후보 유전자들간의 연관성 연구

정인원,김헌,홍주봉,지경환,이규영 大韓神經精神醫學會 2002 신경정신의학 Vol.41 No.6

연구목적 : 알코올 대사와 중추신경계내의 알코올 작용부위와 관련한 일부 후보유전자들이 알코올 의존과 관련이 있는지를 확인하고자 하였다. 방 법 : DSM-IV로 진단된 알코올 의존 환자 128명과 정상 대조군 128명을 대상으로 후보 유전자들의 다형성을 중합효소 연쇄반응과 제한효소처리법을 이용하여 동정하였다. 여기서 분리된 대립유전자와 유전자형에 따른 빈도의 차이를 유전자별로 각각 비교하였으며, 알코올 의존에 작용하는 서로 다른 유전자들에 의한 영향력을 배제하기 위하여 logistic regression 분석을 적용하였다. 결 과 : 알코올 의존군에서는 ALDH_2 유전자의 NN(wild type)형이 정상대조군에 비하여 유의하게 많았다(chi-square test, p<0.001). logistic regression analysis를 통하여 다른 유전자들에 의한 영향을 보정한 상태에서 ALDH_2가 NN(wild type)인 경우 다른 아형에 비하여 알코올 의존에 대한 odds ratio는 130.312이며 그 신뢰구간은 (17.22, 986.43)이었다. 한편, ASA는 N-glycosylation 부위에 변이형 대립유전자를 갖고 있는 경우(AG or GG)는 wild type에 비하여 알코올 의존에 대한 위험도는 2.344배이며 그 95% 신뢰구간은 (1.128, 4.871)이었다. 결 론 : 알코올 의존과 ALDH_2 유전자간에는 밀접한 연관성이 확인되었다. 또한 다른 유전자들은 개별 연관분석에서 의미있는 연관성이 관찰되지는 않았지만 logistic regression analysis를 통하여 N-glycosylation 부위에 다형성이 있는 ASA 유전자가 알코올 의존과 관련이 있음을 시사하였다. Objectives : This study was to explore the association between alcohol dependence and five candidate genes related to the metabolism of alcohol and the enzymes of the suspected sites in CNS. Methods : The genotype and allele frequencies of five candidate genes in 128 male hospitalized patients who met DSM-IV criteria for alcohol dependence were compared with 128 age-matched healthy male control subjects using polymerase chain reaction and restriction fragment length polymorphism. A logistic regression analysis was applied in order to exclude the reciprocal interactions among five candidate genes. Results : The NN genotype frequency of the ALDH_2 gene was significantly higher in alcoholic patients than in control subjects(chi-square test, p<0.001). No difference in frequency was found in the other four genes. In a logistic regression analysis, the odds ratio for alcohol dependence in the NN genotype of the ALDH_2 gene and AG or GG genotypes of the N glycosylation site on the ASA gene were 130.312(95% confidence interval, 17.22-986.43) and 2.344(95% confidence interval. 1.128-4.871), respectively. Conclusion : The result reiterates the association of the ALDH_2 gene polyporphism and the alcohol dependence. Logistic regression analysis additionally suggested that the N-glycosylation site on the ASA gene was associated with alcohol dependence.

충북대학교 병원 응급실을 방문한 자살 기도자의 사회경제학적 특성 연구

김재진,박정래,정인원 충북대학교 의과대학 충북대학교 의학연구소 1996 忠北醫大學術誌 Vol.6 No.1

중소도시인 청주지역의 자살기도자들의 이상적 특성을 조사할 목적으로, 1995년 4월 1일부터 1996년 3월 31일까지 자살기도를 주소로 청주소재의 충북대학교병원 응급실에 내원하였던 102명의 자살기도자에 대한 인구학적 특성과 자살기도의 양상을 조사하여 다음과 같은 결과를 얻었다. 1. 자살기도자의 남녀비는 1:1.9로 여자가 많았고, 연령분포는 20-29세가 46.1%로 가장 많았다. 2. 자살기도자의 생활수준은 중류가 48.6%로 가장 많았고, 교육수준은 고졸이상의 고학력자가 71.2%로 가장 많았으며, 직업 분포에서는 Skilled와 Nonskilled 모두 48.6%를 차지하였다. 3. 자살기도자의 결혼상태에서는 결혼이 50.0%로 가장 많았고, 이혼자의 비율은 단지 5.5%였으나 충북인구 전체의 이혼자 비율인 0.6%와 비교하면 상대적으로 높았다. 4. 자살기도자의 종교 분포에서는 종교 없음이 58.3%로 가장 많았고, 특히 천주교도의 비율이 전체의 1.4%로 청주인구 전체의 천주교도비율인 5.8%보다 낮았다. 5. 자살기도 장소는 자가에서 88.9%, 시간은 오후 6시부터 밤12시 사이에 56.9%, 계절은 여름(6월-8월)에 43.1%의 비율로 각각 가장 높은 비율을 나타내었고, 자살기도의 동기는 애인이나 배우자와의 애정불화가 61.0%로 가장 많았다. 6. 자살기도의 방법에서는 신경안정제나 농약을 음독한 경우가 82.4%로 가장 많았고, 남자보다 여자가 보다 심각하지 않은 방법으로 자살기도를 하는 경향을 보였다. 7. 자살기도자의 정신과적 진단은 우울성 적응장애가 43.2%로 가장 많았다. 8. 정신과 의사에 대한 자문율은 71%였고, 자문이 되지 않은 이유는 타과 및 응급실의사가 자의로 귀가 조치한 경우가 43.3%로 가장 많았다. The object of this study was to investigate demographic characteristics and behavior patterns of the suicidal attempters in small urban area. The subjects were 102 persons who attempted suicide and came to the emergency room of Chungbuk National University Hospital from Aprill 1, 1995 to March, 31, 1996. The results were as follow: 1. Female outnumberd males(male/female ratio 1:1.9) and the most common age group was twenties(46.1%). 2. Large parts of the suicidal attempters were investigated to be middle(48.6%) in economic state, high-school and college graduates(71.2%) in educational state, and no religion(58.3%) in religious state. 3. Divorced proportion of suicidal attempters was relatively high(5.5%) as compared with that(0.6%) of general population of Chungbuk. 4. The most frequent attempts occurred in their own home(88.9%), at 6:00 PM to midnight(56.9%), in summer(43.1%), and because of the conflict with the lover or spouse(61.0%). 5. The most frequent suicidal method was sedative-hypnotics overuse(46.0%), but most method of successive suicide was paraquat ingestion(8/9). Female suicidal attempters tended to use more non serious suicidal method. 6. The most common psychiatric diagnosis of suicidal attempters was adjustment disorder with depression(43.2%). 7. Those who were consulted to psychiatrist were 71% of 102 attempters.

향정신성 약물의 맞춤형 약물치료

정인원,이규영 대한정신약물학회 2002 대한정신약물학회지 Vol.13 No.3

The pharmacotherapeutic responses such as clinical efficacy and adverse events exhibit wide variabilities in individuals and even in different races and populations. The human genetic diversity has been known as the one of the main factors in the variations of drug responses expressed in the area of pharmacokinetics and pharmacodynamics. Polygenetic implications have been suggested in the pathophysiology of psychiatric disorders. The risks in psychiatric disorders could be explored by combining the polymorphisms of multiple candidate genes. This suggests that drug therapy should be tailored to the genetic make-up of the individual. The emerging field of pharmacogenomics could be a landmark for the development of more effective clinical efficacy and less adverse events by individually tailored drugs.

알코올 의존과 일부 후보 유전자들간의 연관성 연구

정인원,김헌,홍주봉,지경환,이규영 대한신경정신의학회 2002 신경정신의학 Vol.41 No.6

항정신병약물에 의한 안구운동발작과 발작성 지각변화 증후군

정인원,김임열,윤탁,정성훈,정희연,김용식 대한조현병학회 2018 대한조현병학회지 Vol.21 No.1

During antipsychotic drug treatment, clinicians occasionally encounter sudden attacks of oculogyric crisis (OGC) and/or paroxysmal perceptual alteration (PPA) which occur mostly in the afternoon or early evening lasting for minutes to hours and are eventually remitted with rests or short sleep and/or medications such as benzodiazepines, anticholinergics and so forth. Moreover, these attacks are usually accompanied with psychiatric symptoms such as various modalities of hallucinations and illusions, delusions, obsessive thoughts, panic attacks, agitation as well as autonomic symptoms. These accompanying psychiatric symptoms can be perceived as a worsening of psychiatric symptoms if the clinician does not understand the symptoms due to the side effects of antipsychotic drugs, which may result in increasing the dosage of antipsychotics instead of reducing doses or switching to less offending drugs. On the other hand, patients could easily recognize the symptoms as the adverse effects of drugs. This literature review and case-series study is aimed to raise awareness of OGC and PPA by providing clinical cases and author’s views with the literature reviews about concepts, recognitions and managements from the works of Japanese authors who first reported the clinical importance of these attacks, particularly PPA.

초발정신분열병

홍주봉,정인원 충북대학교 의과대학 충북대학교 의학연구소 1997 忠北醫大學術誌 Vol.7 No.2

초발(first episode)정신분열병에 대한 연구는 다음과 같은 장점을 가지고 있다. 1) 정신분열병의 질병경과에 의해 생긴 문제나 약물치료에 의해 생기는 교란효과를 최소화 할 수 있으며, 2) 발병시기에 질병의 원인이나 정신병리학적으로 중요한 역할을 하는 생물학적 또는 심리적 요인을 찾아낼 가능성이 높으며, 3) 원인, 경과, 예후에 대한 전향성 연구를 할 기회를 가질 수 있다 그래서 이런 장점들 때문에 초발정신분열병에 대한 연구가 활발해지고 있다. 저자들은 이 초발정신분열병에 대해 연구한 결과들을 정리해 정신분열병을 좀더 이해하는데 도움이 되고자 하였다. 이 소고에서는 만성정신분열병과 비교하여 초발정신분열병의 자연적 경과, 뇌의 형태와 기능, 예후를 알아보았다. Study of first episode schizophrenia has several advantages; 1) the confounding effects of chronicity and pharmacotherapy can be minimized, 2) the biological or psychological fators that are etiologically or pathophysiologically significant may be detected more at illness onset, 3) the opportunity to carry out prospective studies of biology, course, and outcome can be increased. The natural course, brain dysfunction, and outcome in first episode schizophrenia were reviewed in comparison with multiple treated schizophrenia.