흰쥐의 중추성 Serotonin 고갈이 강제수영 중 부동자세 시간, 불안 및 수동적 회피 학습에 미치는 효과

박제민,김종백,강철중 大韓神經精神醫學會 1996 신경정신의학 Vol.35 No.3

흰쥐에서 p-chlorphenylalanine(PCPA)로 인한 강제수영 중 부동자세 시간의 단축이 불안이나 수동적 회피 학습 능력의 변화와 관련된 것인가를 검증하고자 하였다. 흰쥐에게 PCPA 300mg/kg 혹은 생리식염수를 하루 한 번 연속 3회 복강내 주사하였다. 마지막 주사 24시간 후에 공간에서의 활동성(ACT0), 높은 십자 통로 실험에서 개방 통로에 머무는 시간(ANX0), 왕복 회피상자에서 통과 지연 시간(STL0) 등을 측정하고 0.5mA 전기자극을 3초간 주어 회피 반응을 학습시켰다. 그리고 15분간 강제수영시켰다. 다음 날 같은 방법으로 활동성(ACT1), 불안(ANX1), 수동적 회피 반응 학습 정도(STL1), 5분간의 강제수영 중 총 부동 자세 시간 등을 측정하였다. 마지막 약물 혹은 대조액 투여 7일 후 수동적 회피 학습 유지 정도(STL7)를 다시 측정하였다. 결과는 아래와 같다. 1) 전체 대상군에서 ACT1은 ACT0보다 감소하였다. PCPA는 개방공간에서의 활동성에 영향을 주지 않았다. 2) PCPA 군은 높은 십자 통로 실험에서 ANX0와 ANX1 둘 다 대조군 보다 유의하게 길었다. 3) STL1은 PCPA군과 대조군 모두 STL0 보다 유의하게 지연되었다. PCPA는 STL0 이나 STL1에 영향을 주지 않았다. 그러나 대조군은 수동적 회피 학습 7일 후에도 통과 지연 시간이 유의하게 연장되어 있는데 반하여 PCPA군은 STL7이 STL0과 유의한 차이가 없었다. 4) 강제수영 중 부동자세 시간은 PCPA군이 대조군보다 유의하게 짧았다. 이상의 결과에서 PCPA 투여로 인한 강제수영 중 부동자세 시간의 단축은 PCPA가 비특이적 신체 활동을 증가시키거나 수동적 회피 반응 습득을 방해함으로써 일어나는 현상이 아니며, 진정 작용없이 탐색 행동을 증가시키거나, 스트레스 하에서의 행동 억제 현상을 차단함으로써 강제수영 중 부동자세 시간을 단축시킨다고 추론한다. 아울러 PCPA가 기억 고정 과정을 방해할 가능성이 있음을 제안한다. Purpose : The test if p-chlorophenylalanine(PCPA) induced decrease of immobility time during forced swimming test in rats is an epiphenomenon related with PCPA-induced changes in anxiety level or learning ability. Methods : 22 male rats(Sprague Dawley, weighting 180-280gm) were randomly assigned to PCPA or control group and treated with 300mg/kg of PCPA or saline i.p. at -72, -48, and -24 hrs. Number of segment(ACT0) entered with 4 limbs on the open field(L100×W100×H40cm, 25 segments), time(ANX0, sec) spent on the open arm(L110×W10cm, 50cm from the ground) in the elevated plus maze, and step-through latency(STL0, cut-off time : 300sec) in the shuttle box(L76.2×W34.3×H50.8cm, 7.5w electric bulb in the light chamber, 0.5mA for 3 sec in the dark chamber) were measured consequently at 24hrs after the last injection of PCPA or saline. After 20min of rest, animals were forced to swim for 15 min(cylinder : φ18×H40cm ; water : H15cm, 25℃). On the next day, the second trial of open field test(ACT1), elevated plus maze test(ANX1), passive avoidance learning test(STL1), and measurement of total immobility time(IT, sec) during the 5min of forced swim were done in the same manner as the first trial except that electrical shock was not given to the animals in the passive avoidance learning test and duration of forced swimming was shortened from 15min to 5min. To evaluate longterm effect of PCPA on maintenance of memory, measurement of step-through latency was repeated 7 days after the first trial(STL7). Result: 1) ACT1 was significantly decreased in the pooled sample, but the effect of PCPA on the general motor activity was not significant. 2) PCPA significantly prolonged the time spent on the open arms in the elevated plus maze test. 3) Comparing to STL0, STL1 was significantly prolonged in both groups. PCPA did not affect STL0 or STL1. STL7 was significantly prolonged in the control group, but not in the PCPA group. 4) PCPA shortened IT significantly. Conclusion : PCPA-induced decrease of immobility time during the forced swimming test in rats seems to be related with disinhibition of stress-related behavioral suppression. PCPA does not affect acquisition and short-term maintenance of passive avoidance learning, but necessity of further studies about its effect on long-term maintenance on memory is raised.

섬망에서 Risperidone의 치료효과

강철중 부산대학교 병원 암연구소 2002 부산대병원학술지 Vol.- No.12

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.

여성 알코올 의존과 μ 아편계 수용체 유전자형과의 연관 연구

강철중,김성곤,변원탄,김윤진,황인복,김성연 대한정신약물학회 2005 대한정신약물학회지 Vol.16 No.6

Objectives: Previous studies have shown that the endogenous opioid system, which plays an important role in drinking behavior, might be related to the genetic etiology of alcohol dependence. And a recent study reported that the affinity of μ opioid receptor, which is closely related to the endogenous opioid system activity, is affected by the genotype of μ opioid receptor gene(OPRM1) A118G. To investigate the gender difference in genetic etiology of alcohol dependence, this study examined the association of the genotype of OPRM1 A118G with female alcohol dependence in Koreans. Methods: The author studied the genotype of OPRM1 A118G in 106 male and 35 female Korean with alcohol dependence and 80 male and 60 female healthy Koreans as control. Results: 1) A statistically significant increase in A/G or G/G (G+) genotype of OPRM1 A118G was observed in women with alcohol dependence compared to the controls. 2) Among men with alcohol dependence, no significant difference in OPRM1 A118G polymorphism was observed relative to the age at which drinking started, age of onset of alcohol-related problems, age of first admission to psychiatric hospital for alcohol-related problems, drinking days per month, drinks per drinking day, family history of alcohol dependence in the first-degree relatives or history of severe alcohol withdrawal symptoms. But the drinking days per month is significantly less in those who have A/G or G/G genotypes of OPRM1 A118G. Conclusion: These results suggest that G+ genotypes of μ opioid receptor gene A118G are important genetic factors in the etiology of female alcohol dependence.

정신분열병환자에서 Taq I A 도파민 $D_2$ 수용체 다형성과 항정신병약물의 치료반응과의 연관

강철중,Kang, Cheol Joong 대한생물정신의학회 2005 생물정신의학 Vol.12 No.2

Purpose:In an attempt to predict the interpersonal differences of therapeutic response to antipsychotic drugs on pharmaco-genetic bases, this study was designed to investigate the relationship between the therapeutic response to antipsychotic drugs and Taq I A dopamine $D_2$ receptor polymorphism in schizophrenic patients. Methods:The subjects were 158 patients diagnosed with schizophrenia(DSM-IV). The therapeutic response to antipsychotic drugs was evaluated using the Treatment Response Scale(TRS) retrospectively. Patients were divided into two groups, dopamine receptor antagonist responders, and serotonin-dopamine antagonist responders. The patients' Taq I A dopamine $D_2$ receptor polymorphism was determined by polymerase chain reaction(PCR) and restriction fragment length polymorphism(RFLP). Results:The dopamine receptor antagonist responders had the A1 allele in significantly higher incidences (${\chi}^2$(1)=4.875, p=0.027, two-tailed). No significant difference was found among the serotonin-dopamine antagonist responders between those with or without the A1 allele. Conclusions:The patients with the A1 allele responded better to dopamine receptor antagonists than those with no A1 allele. Based on these results, it is suggested that the pharmacological effect of dopamine receptor antagonists can be predicted depending on the presence of the A1 allele in schizophrenic patients.

경계성 인격 장애 환자의 정신치료 상황에서의 거리문제

강철중,박숙현 부산대학교 병원 암연구소 2006 부산대병원학술지 Vol.- No.20

From the first contact between therapist and patient, establishing optimal distance is a high priority. Borderline patients repeatedly test the professional boundaries of the relationship and often directly or indirectly express a wish for a parent rather than a therapist. Early in the psychotherapy process, the therapist often feels a sense of floundering and an inner urgency to act rather than reflect. Because of the potential for pharmacotherapy to be contaminated by countertransference responses, a rational and systematic approach to medication, based on target symptoms and trait vulnerabilities, must be part of the overall treatment plan. Establishing a therapeutic frame and a contractual understanding is a useful way to construct an analytic space with the patient in which psychotherapy can take place. Matters such as fee payment, the length of sessions, the handling of vacations, the frequency of sessions, the need for psychiatric hospitalization, the management of suicidal crises, and a policy on phone calls should be part of this contract. On the other hand, a good deal of countertransference enactment can hide behind the rigid adherence to an inflexible structure. The balance between flexibility and boundaries parallels the therapist’s oscillation between playing the role of a new object in the present and an old object from the past.

高麗 時代 律賦 硏究

姜哲中 慶尙大學校 南冥學硏究所·韓國漢詩學會 1999 硏究發表大會 Vol.- No.9

한국인 남녀 알코올 의존 환자에서의 알코올 대사 효소 유전자 다형성에 관한 연구

강철중(Cheol-Joong Kang),김성곤(Sung-Gon Kim),김현경(Hyeun-Kyeung Kim),황인복(In-Bok Hwang),변원탄(Won-Tan Byun) 대한생물치료정신의학회 2006 생물치료정신의학 Vol.12 No.1

Objective : Alcohol is metabolized in hepatocyte through alcohol dehydrogenase(ADH), microsomal ethanol oxidizing system (MEOS) and catalase. In cases of alcohol dependence, the activity level of the MEOS increases, especially Cytochrome P₄?? 2E1 (CYP2E1). The goal of this study was to investigate whether the CYP2E1 polymorphism is associated with alcohol dependence, and to investigate gender differences in the frequencies of CYP2E1 genotypes and allels. Method : The subjects were Korean male(n=104) and female(n=40) alcohol dependent patients diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-Ⅳ). Control groups were healthy Korean male(n=79) and female(n=59) subjects who do not drink over five standard drinks per month. Subjects' CYP2E1 polymorphisms(RsaⅠ+PstⅠ, OraⅠ and TaqⅠ) were determined by a polymerase chain reaction(PCR) and restriction fragment length polymorphism (RFLP). Results : 1) In male subjects, there was no association between alcoholics and control groups in the genotype frequency and the allele frequency of the three polymorphisms of CYP2E1. 2) In female alcoholics, the frequency of the A1A1 and A1A2 genotypes of the Taql polymorphism was significantly higher than in the female control groups(df=2, χ²=6.42, p=0.04), while other frequency levels of genotypes and alleles were not significant. Conclusion : These findings suggest genetic associations between CYP2E1 polymorphism and female alcohol dependence but not male. 목적 : 알코올 의존의 발생에서 유전적 원인이 남녀간에 다를수 있음을 보여주는 선행 연구 결과들이 있다. 따라서 알코올 대사 효소 유전자들의 유전적 중요성이 남녀간 차이가 있을 것이라는 가설 하에 한국인 알코올 의존 환자와 정상인을 대상으로 cytochrom P4502El(CYP2E1) 유전자의 5’ -flank 부위(제한효소 Rsa Ⅰ과 Pst Ⅰ), intron 6 부위 (제한효소 DraⅠ) 및 intron 7 부위 (제한효소 Taq Ⅰ)의 유전자형의 빈도를 조사하고 남녀 각각 차이가 있는지를 비교 분석하였다. 방법 : 알코올 의존 환자 144명 (남자 104명, 여자 40명)과 정상인 138영(남자 79명, 역자 59명)을 대상으로 CYP2E1유전자의 5’ -flank 부위(제한효소 Rsa Ⅰ과 Pst Ⅰ) 의 c1c1과 c1c2 및+c2c2(이하 c2+) 유전자형, intron 6 부위(제한효소 Dra Ⅰ) 의 DD와 DC+CC(이하 C+) 유전자형 및 intron 7 부위(제한효소 Taq Ⅰ) 의 A2A2와 A2A1+A1A1(이하 A1+) 유전자형에 빈도를 남녀 각각 비교하였다. 유전자형의 분석은 말초혈액 백혈구에서 DNA를 분리한 후 PCR-RFLP 방법을 이용하여 실시하였다. 결과 : CYP2E1 유전자의 5’ -flank 부위의 유전자형의 빈도와 intron 6 부위 유전자형의 빈도에서는 남자 혹은 여자 알코올 의존환자 모두 남자 혹은 여자 정상대조군과 유의한 차이가 없었다. 한편, intron 7 부위 유전자형의 빈도에 있어서는 여자 알코올 환자가 여자 정상대조군에 비하여 A1A1, A1A2의 빈도가 유의하게 높게 나타났으나, 남자는 유의한 차이가 없었다. 결론 : 이러한 결과는 여성에서의 알코올 의존 발생에 CYP2E1 유전자의 intron 7 부위(제한효소 Taq Ⅰ) 유전적 다형성이 중요하다는 것을 제시하고 있다.

한국민담 "바늘 상자 속에 넣어 둔 눈알"에 대한 분석심리학적 해석

강철중 ( Cheol Joong Kang ) 한국분석심리학회 2008 心性硏究 Vol.23 No.1

The Korean fairytale `Eyes in the Sewing Box` is a story about a boy who was abandoned by his mother and searches to find own father. The father was exiled to a distant place and the boy lived with his stepmother. One day, his stepmother told him that his father got a serious disease and he needed fresh human eyes for a cure. The boy took out his eyes and gave them to his mother. But the story was a lie and it was her plan to abandon her son. She put her son`s eyes into her silk pouch and kept them in her sewing box. The boy`s stepmother abandoned the boy and brought him to a riverside very far from their home. Because of his blindness, he could not find where to go. He was completely lost and finally he fell into a river. But fortunately he landed on an island. He found a bamboo grove and heard some beautiful sounds which came from the bamboo. He wanted to find where the sound came from. He grabbed the bamboo one by one, finally he found it. Then he cut the bamboo and made a flute. He sat there and played the bamboo flute every day, all day long. The sound was extremely beautiful and emotional. Everybody who heard the sound was touched by it. One day, a local judge heard the sound and ordered his servant to find the person who played the flute. The servant brought the boy in front of the judge. The judge asked him about his story, how he became blind, and why he played the bamboo flute. The boy told him his entire story. Just then, his father heard the story of the boy in the crowd. Finally the boy and his father met again. They went back to their home and found his eyes. The boy`s vision was restored and he forgave his mother. They lived together happily ever after. This story is about a boy who loses his father and who is reunited with his father again. Immature consciousness cannot stand individually, so it is helpless under the influence of negative mother archetype. Additionally, it takes out the vision of consciousness. The consciousness isolated in the lonely island, and surrounded by unconsciousness. But the island is individual space, though it is very small and lonely. From there, the sound is produced spontaneously. That is the sound of the Self. The consciousness does not ignore the sound from the Self, finally it gets back its` paternity and achieves higher consciousness.

알코올 의존환자에서 갈근이 알코올 갈망과 대뇌 국소혈류량의 변화에 미치는 영향

강철중,김명정,김성곤,김인주 大韓神經精神醫學會 1997 신경정신의학 Vol.36 No.5

알코올 의존 환자에서 갈근이 알코올 갈망을 감소시킨다는 보고가 있고 알코올 갈망에 관여하는 대뇌부위가 전두엽-시상-선조체-측좌핵을 포함하는 회로라는 학설이 있다. 저자는, 갈근이 이러한 부위의 혈류량에 어떤 영향을 미치는지 알아보기 위해 연구를 실시하였다. 알코올 의존으로 입원하여 급성중독과 금단증상에서 회복된 환자를 대상으로 실험 제 1일에 알코올 갈망, 불안 및 기분을 측정한 후 단일광자광출전산화단층촬영술을 이용하여 양측 미상핵 두부, 양측 시상 및 양측 안와전두엽의 국소 혈류량을 측정하였다. 실험 제 3일에 소량의 알코올음료를 마시게 한 후에 제 1일의 실험을 반복하였다. 제4일부터 제13일까지 건조 갈근과립 12gram을 1일 2회 분복시키고 제11일과 제13일에 각기 제1일과 제3일의 실험을 동일한 방법으로 실시하였다. 그 결과는 아래와 같다. 1) 갈근 투여 전에는 음주 전에 비해서 음주 후에 알코올 갈망이 유의하게 증가하였으며 이때 우측 미상핵의 두부에서 혈류량이 유의하게 증가하였다. 2) 음주하지 않은 상태에서 갈근 투여 전과 후를 비교한 결과, 갈근 투여 후에는 알코올 갈망이 유의하게 감소하였으며 이때에 우측 미상핵의 두부와 좌측 안와전두엽에서 유의한 혈류량의 증가를 보였다. 3) 음주한 상태에서, 갈근 투여 전과 후를 비교하면, 갈근 투여 후에는 양측 미상핵 두부와 양측 시상에서 유의한 혈류량의 감소를 보였다. 4) 갈근 투여 후에는 음주 전에 비해서 음주 후에 알코올 갈망의 증가를 보이지 않았으며, 양측 미상핵 두부의 혈류량은 감소하였다. 저자는 이러한 결과에서, 갈근이 알코올 의존환자에서 기초 음주 욕구를 감소시키고 음주 후에 유발되는 알코올 갈망의 증가를 차단하며 이러한 음주욕구의 변화와 변연계선조체 특히 미상핵의 국소 혈류량의 변화 사이에 의미있는 연관성이 존재할 것으로 시사한다. In light of recent reports of the effectiveness of Radix puerariae in the alcoholics and recent formulation of a hypothesis that craving for alcohol in the alcohol-dependent individual is mediated by a limbic circuit involving the fronto-thalamic and fronto-striatoaccumbal region, the authors studied the effect of Radix puerariae on craving for alcohol and cerebral blood flow(rCBF) of these regions. The subjects were hospitalized patients with alcohol dependence recovered from acute intoxication and withdrawal symptoms. On the first day of experiment, rCBF in the areas of caudate nuclei, thalamus and orbitofrontal cortices was measured by Single-Photon Emission Computed Tomography. On the third day, the same procedure was repeated after intake of a small priming dose of alcohol. Radix puerariae in dose of 12gm/day for 10 days was given from fourth day of experiment to the thirteenth day and on the eleventh and thirteenth days, the measurements of rCBF were repeated in the same method as in the first and third day, respectively. Immediately before measurements of the rCBF in each experiment, craving for alcohol was measured by means of Visual Analogue Sale. The results were as follows : 1) Before the treatment of radix puerariae, the alcohol-dependent patients developed a significant alcohol-induced alcohol craving and a concomitant increase of rCBF in the right head of caudate nucleus. 2) Radix puerariae significantly lowered alcohol craving and significantly increased rCBF in the right head of caudate nucleus and the left orbitofrontal cortex in alcohol-free, basal condition. 3) After the treatment of radix puerariae, the rCBF after alcohol intake in bilateral caudate nuclei and bilateral hemithalami was significantly decreased. 4) Radix puerariae did not induce post-alcohol craving for alcohol and significantly decreased post-alcohol rCBF in bilateral caudate nuclei. From these results, it is suggested that Radix puerariae decreases basal alcohol craving in the alcohol-dependent patients, and further that there may exist a significant association between these changes of alcohol craving and concomitant changes of rCBF in the limbic striatim, especially caudate nucleus.