Rim1α and Neurexin3 Regulate Synaptosomal Dopamine Release

Sang Kyeong Lee(이상경),Joo-Cheol Shim(심주철),Young-Hoon Kim(김영훈),Bo-Geum Kong(공보금),Dae-Hyun Seog(석대현) 한국생명과학회 2009 생명과학회지 Vol.19 No.9

신경전달물질의 분비는 시냅스전 신경말단의 active zone에 있는 다양한 단백질들에 의해 조절된다. 도파민은 정신분열병, 약물중독과 같은 여러 가지 행동, 정신질환의 병태생리와 연관된 필수적인 신경전달물질이다. 저자들은 본 연구에서 신경전달물질 분비와 관련된 주요 유전자가 결여된 knockout (KO) 생쥐의 시냅토좀(synaptosome) 도파민 분비를 측정하였다. 시냅토좀 도파민 흡수와 분비는 [³H]-도파민과 관류실험을 이용하여 시행, 측정하였다. 17 KO 생쥐 가운데 3 종류의 생쥐에서 그들의 littermate 대조군과 비교하였을 때 변화된 도파민 분비를 보였다. Rim1α KO에서 세포막 탈분극에 의한 [³H]-도파민은 유의하게 감소되었으며, 또한 Rim1α의 도파민 신경에서의 조건 KO에서는 생리적 완충용액에 의한 기본적인 도파민 분비 및 세포막 탈분극에 의한 도파민 분비 모두가 유의하게 감소되어 있었다. neurexin3의 도파민 신경에서의 조건 KO에서는 세포막 탈분극에 의한 도파민 분비의 증가를 보였다. 이 데이터들은 도파민 분비와 글루타메이트, GABA와 같은 전통적 신경전달물질 분비의 유사성과 차별성을 설명한다. 결론적으로, Rim1α와 neurexin3는 시냅스전 도파민 분비의 중요한 조절자이며 신경계 질환과 연관될 가능성이 있다. Neurotransmitter release is regulated by various proteins of the active zone in the presynaptic nerve terminals. Dopamine (DA) is an essential neurotransmitter associated with the pathophysiology of diverse behavioral and mental illness such as schizophrenia and drug addiction. We measured synaptosomal DA release of knockout (KO) mice which lacked major genes related to neurotransmitter release. Synaptosomal DA uptake and release were performed and measured using [³H]-DA and superfusion experiments. 3 of the 17 KO mice exhibited altered DA release compared to their littermate controls. In Rim1α KO, [³H]-DA release evoked by membrane depolarization significantly decreased. Both basal (physiological buffer-evoked) and membrane depolarization-evoked DA release significantly decreased in dopaminergic conditional KO of Rim1αβ. Dopaminergic conditional KO of neurexin3 demonstrated a significant increase of membrane depolarization-evoked DA release. These data explain the similarities and distinctions between DA and other classical neurotransmitters such as glutamate and GABA (γ-aminobutyric acid) release. In conclusion, Rim1α and neurexin3 may be important regulators of presynaptic DA release and related to disorders of the nervous system.

조현병 환자에서 QT 간격 지연과 흡연의 연관성

박민경(Min-Kyung Park),심주철(Joo-Cheol Shim),공보금(Bo-Geum Kong),강제욱(Je-Wook Kang),문정준(Jung-Joon Moon),신혜경(Hye-Kyung Shin),김현정(Hyun-Jung Kim),김정민(Jung-Min Kim),오민경(Min-Kyung Oh),정도운(Do-Un Jung) 대한생물치료정신의학회 2012 생물치료정신의학 Vol.18 No.2

Objectives:Abnormalities in the QT interval have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is no clear correlation between cigarette smoking and QT interval prolongation in schizophrenia. The purpose of this study is to evaluate the effects of cigarette smoking on the QT interval and estimate the prevalence of prolonged QT interval in schizophrenic patients who take antipsychotics. Methods:We studied 106 schizophrenic patients taking antipsychotics and age- and sex-matched 106 people in control group. A prolonged QTc interval was defined as >450 msec in men and >470 msec in women. The demographic data and clinical characteristics of subjects were collected from medical records. The correlations between QTc interval and other variables were assessed using a regression analysis. Results:There was no significant association between cigarette smoking and QT interval. The mean QT interval was not significantly influenced by antipsychotic dose and type of antipsychotics. However, there was significantly prolonged QT interval in schizophrenic patients(421.1±25.7 msec) compared to control group(412.1±17.1 msec) (p=0.003). The prevalence of prolonged QT interval in schizophrenic patients was 6.6%(7 of 106 patients). Five patients( 71.4%) were smoker and six patients(85.7%) had obesity. By contrast, nobody had a prolonged QT interval in control group. Conclusions:The prevalence of prolonged QT interval was relatively high among middle aged schizophrenia patients. And there was significantly prolonged QT interval and higher body mass index in schizophrenia patients.

조현병 환자에서 정신병리와 인지 기능과의 연관성

김성진(Sung-Jin Kim),심주철(Joo-Cheol Shim),공보금(Bo-Geum Kong),강제욱(Je-Wook Kang),문정준(Jung-Joon Moon),임지섭(Ji-Seop Lim),김임규(Im-Gyu Kim),김연수(Yeon-Sue Kim),오민경(Min-Kyung Oh),정도운(Do-Un Jung) 대한생물치료정신의학회 2013 생물치료정신의학 Vol.19 No.2

Objectives:Cognitive dysfunction is one of the major symptoms of schizophrenia, and has a diverse effect on the prognosis and course of schizophrenia. Several studies have been done about the correlation between cognitive dysfunction and clinical symptoms of schizophrenia, but the results of those studies were not clear. This study was performed to confirm the correlation between cognitive dysfunction and clinical symptoms of schizophrenia. Methods:We studied 117 patients with schizophrenia. We assessed clinical symptoms and the cognitive function of the patients, and analyzed the statistical correlation between clinical symptoms and the cognitive function. For clinical symptoms, Positive and Negative Syndrome Scale(PANSS), Clinical Global Impression-Severity(CGI-S) and Hamilton Depression Rating Scale(HDRS) were performed. For cognitive function, Digit Span Test, Visual Span Test, Stroop Color Word Test(SCWT), Continuous Performance Test(CPT), Wisconsin Card Sorting Test(WCST), and Digit Symbol Substitution Test(DSST) were performed. Results:There was significant correlation between CPT and clinical symptoms. The WCST revealed that Categories Achieved(CA) have significant correlation with disorganization symptoms among 5-factor model of PANSS (p<0.05). DSST revealed that the total score(p<0.01), negative syndrome(p<0.01), general psychopathology(p<0.01) among 3 kind major area classification of PANSS and disorganization symptoms of 5-factor model of PANSS(p<0.001) have significant correlation. Conclusion:This study revealed the correlation between the cognitive function and a part of clinical symptoms in patients with schizophrenia, as shown through the CPT, WCST and DSST.

60세 이상 노인 인구에서 인지기능과 우울증, 자살사고, 혈청지질농도와의 연관성

문정준,이봉주,김정은,김우진,김민효,박민경,송태홍,심주철,김경미,이정구,김영훈,Moon, Jung-Joon,Lee, Bong-Ju,Kim, Jeong-Eun,Kim, Woo-Jin,Kim, Min-Hyo,Park, Min-Kyong,Song, Tae-Hong,Shim, Joo-Cheol,Kim, Gyung-Mee,Lee, Jung-Goo,Kim, Young 대한생물정신의학회 2010 생물정신의학 Vol.17 No.4

Objectives : We investigated a correlation of cognitive function, depression, suicidal idea and serum lipid levels in Korean elderly over 60 years old to find risk factors of deprssion and cognitive decline. Methods : 834 persons participated in this study. Clinical evaluation was done at a point by using Mini-Mental State Examination in the Korean version of CERAD assessment packet(MMSE-KC). We also evaluated 165 persons that agreed to our exact examination for Geriatric Depression Scale(GDS), Scale for Suicidal Ideation(SSI), Hachinski Ischemic Score and serum lipid profile. Correlation analysis was used to evaluate correlation among serum lipid levels, MMSE-KC and SSI. One-way ANOVA was used for comparison of serum lipid levels and cognitive function, depression and SSI. We did a post-hoc analysis. Results : Depression and suicidal ideation were related with cognitive impairment in Korean elderly over 60 years old. Those who have more severe cognitive impairment and depressive symptom, have higher Hachinski ischemic score. We can see high HDL cholesterol levels only in the normal control group. Low total, HDL, LDL cholesterol were related with depression. Conclusion : There was high prevalence of depression in the Korean elderly over 60 years old and low serum lipid level was related with severity of depression and high suicidal ideation. In the normal control group, we can see high HDL cholesterol levels. To confirm this result, we need well-designed and wide range study.

조현병 환자에서 Paliperidone Extended Release의 효능, 안전성 및 내약성 : 48주 개방형, 전향적 연구의 24주 중간 분석

최유라,정동청,김은영,김세현,이현정,이남영,장성만,심주철,주은정,김재진,이상혁,정영철,김용식,안용민,Choi, You Ra,Jung, Dong Chung,Kim, Eun Young,Kim, Se Hyun,Lee, Hyun Jeong,Lee, Nam Young,Chang, Sung Man,Shim, Joo Cheol,Joo, Eun Jeong,Kim, Jae 대한생물정신의학회 2013 생물정신의학 Vol.20 No.1

Objectives We investigated the tolerability, safety, and treatment response to flexible-dose paliperidone ER in patients with non-acute schizophrenia in whom previous antipsychotic drugs were ineffective. Methods This 24-week interim analysis of the 48-week multicenter, prospective, open-label study assessed effectiveness using the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression-Schizophrenia-Severity (CGI-SCH-S) Scale, Personal and Social Performance (PSP) and Drug Attitude Inventory (DAI). Safety and tolerability were assessed using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) and Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS). Results Effectiveness was assessed in 169 patients. Significant improvement in the PANSS total score was observed by week-1 and continued until week-24. The response rate was 33%. The CGI-SCH-S and PSP total scores significantly improved during 24 weeks ; however, no change occurred in the total DAI. Fifty-nine percent of patients reported adverse events, of which extrapyramidal symptoms were the most frequent (19.0%). The DIEPSS and LUNSERS scores were improved after 24 week. Conclusions Switching to the flexible-dose paliperidone ER from an ineffective antipsychotic drug was safe, tolerable, and showed a good treatment response in Korean patients with schizophrenia.

알코올 의존 환자에서의 12단계 척도의 신뢰도와 타당도 연구

정성수(Sung Soo Jung),하태민(Tae Min Ha),김경승(Kyung Seung Kim),이성근(Seong Keun Lee),심주철(Joo Cheol Shim),공보금(Bo Geum Kong),정도운(Do Un Jung) 대한생물치료정신의학회 2014 생물치료정신의학 Vol.20 No.1

Objectives:This study is aimed to assess the reliability and validity of the Twelve Step Scale which are newly developed to observe the direct effect of the twelve step facilitation therapy that has been widely used for the treatment of patients with alcohol dependence. Methods:110 patients who were diagnosed with alcohol dependence by psychiatrists using DSM-TR criteria agreed to participate in the study. Subjects were assessed by questionnaires including demographic data and alcohol related clinical rating scales such as Twelve Step Scale, Korean version of Alcohol Use Disorders Identification Test, Alcohol Dependence Scale, Hanil Alcohol Insight Scale when informed consents were acquired. Four weeks later after initial assessment, Twelve Step Scale was reassessed for subjects who were treated over 3 months at the same hospital without recent admission or discharge for a month. Results:The average of the Twelve Step Scale was higher in female patients than in male. In addition, there is positive correlation between HAIS and Twelve Step Scale. According to factor analysis, Twelve Step Scale has two factors. The results showed significant internal consistency reliability(Cronbach’s α=0.92) but did not show reasonable test-retest reliability. Conclusion:This study showed that the Twelve Step Scale had reasonable reliability and validity except test-retest reliability. Thus the Twelve Step Scale can be used to assess the direct effects of twelve step facilitation therapy, which in turn might contribute to enhance twelve step facilitation therapy in the future.

알콜리즘에서 Buspirone에 대한 Cortisol과 Prolactin 반응

심주철,이정구,김정익,이유철,김영훈 大韓神經精神醫學會 2001 신경정신의학 Vol.40 No.2

연구목적: 본 연구는 buspirone에 대한 cortisol과 prolactin 반응을 통해 알콜리즘에서 5-HT1A 수용체기능을 조사하고자 하였다. 방법: 알콜리즘 환자군은 DSM-IV의 알콜리즘 진단기준에 부합되고 금주기간이 최소 3개월 이상이며 우울 및 불안증상이 없는, 한 정신병원 알콜 센터에 입원한 22명의 남자 환자였다. 대조군은 정상성인 남자 15명이었다. 이들에게 오전 9시에 5-HT□ 효현제인 buspirone 30mg을 경구 투여한 후 0, 30 , 60, 90, 120, 150분의 혈청 cortisol과 prolatine 농도를 측정한다. 결과: 환자군과 대조군간에 cortisol 기저치에는 유의한 차이가 없었다. Buspirone 투여 후 혈청 cortisol 농도는 정상대조군에서는 기저치에 비해 유의한 증가를 보였으나(p<0.01) 환자군에서는 유의환 증가가 없었다. 혈중 cortisol 농도는 buspiron 투여 60분 이후부터 환자군에서 정상 대조군에 비해 유의하게 저하되어 있었다(p<0.05). Buspirone에 대한 혈청 prolactin 반응은 환자군과 정상대조군간에 유의한 차이가 없었다. 결론: Buspirone 투여 후 둔마된 혈청 cortisol 반응을 통해 알콜리즘에 5-HT1A 수용체 반응성이 둔마되어 있음을 확인할 수 있었다. Objectives: The purpose of this study was to evaluate the prolactin and cortisol responses to 5-HT1A receptor activation by buspirone in alcoholics. Methods: The subjects were twenty two male alcoholic patients meeting the DSM-IV criteria for alcohol dependency and abstaining for more than 3 months. Patients were free from overt anxiety and depressive symptoms. Controls were fifteen male normal volunteers, with no psychiatric and medical illness. Blood samples for the measurement of serum cortisol and prolactin levels were drawn 0, 30, 60, 90, 120, 150 minutes after oral administration of 30mg buspirone hydrochloride at 9:00a.m. Results: The baseline cortisol levels were not significantly different between alcoholics and controls. Serum cortisol levels of controls after buspirone administration were significantly increased over time(p<0.01), but those of alcoholics did not increased. After 60 minutes following buspirone administration, cortisol levels were significantly lower in alcoholics than in contrlos(p<0.05). Prolactin responses to buspirone were not significantly different between the two groups. Conclusions: Our results suggested that 5-HT1A receptor function is decreased in alcoholic patients.

정신분열병 환자 가족을 위한 한 정신교육적 가족치료 모형의 효과

이영호,심주철,이상경,서영수,김용관,김규수,김영훈 大韓神經精神醫學會 2000 신경정신의학 Vol.39 No.3

연구목적 : 본 교실에서 정신분열병 환자 가족을 대상으로 시행 중인 장기 정신교육적 가족치료모형을 소개하고, 이모형이 가족의 대처방식과 우울증상, 환자가 자각하는 가족의 정서적 지지와 우울증상, 재입원율 및 사회재활상태에 미치는 영향을 평가하였다. 방 법 : 연구대상은 DSM-IV 진단기준에 의해 정신분열병으로 진단받고 외래 통원치료를 받고 있는 환자와 그 보호자였다. 교육군은 전체 19회 교육 중 최소 ⅔이상 참여한 11명의 환자와 가족이었고 비교육군은 부산소재의 종합병원에서 가족교육을 받지 않고 통원치료만을 받았던 11명의 환자와 가족이었다. 정신교육적 가족치료 모형의 효과는 가족의 대처방식과 우울증상, 환자가 자각하는 가족의 정서적 지지와 우울증상, 재입원율, 사호재활 실태로 나누어 평가했다. 평가도구는 The Ways of Coping Checklist의 국내번안용, Family Emotional Support Questionnaire for Transaction. Beck Depression Inventory를 이용했다. 재입원율 및 사회재활 실태에 대한 평가는 환자 및 가족과의 면담을 통해 조사했다. 결 과 : 본 연구의 정신교육적 가족치료 모형 실시 후 가족의 대처방식 중 적극적 대처는 교육군운 의미있게 증가한 반면 비교육군에서는 변화가 없었다. 소극적 대처 교육군은 의미있게 감소했으나 비교육군에서는 변화가 없었다. 가족치료모형 실시 전 가족들은 양군 모두 심한 우울증상을 갖고 있었다. 가족치료모형 실시 후 가족의 우울증상은 교육군에서 감소, 비교육군은 증가를 보였으나 통계적 유의성은 없었다. 환자가 지각하는 가족의 정서적 지지 평가척도점수는 교육군은 의미있는 증가를 보였으나 비교육군에서는 변화가 없었다. 환자의 우울증상의 교육군에서는 현저한 감소를 보인 반면 비교육군은 상반되게 증가했다. 가족의 적극적 대처가 환자가 자각하는 정서적 지지의 증가 및 우울증상 감소와 의미있는 상관관계를 나타냈다. 또한 교육군의 환자들이 비교육군의 환자들보다 장기가족교육 종료시점과 9개월 경과 후의 추적 평가에서 재입원율이 현저히 낮았고, 사회재활상태도 좋았다. 결 론 : 본 연구에서 실시된 장기 가족교육모형은 가족의 대처방식을 향상시키고, 우울증상의 감소를 가져오며, 환자가 자각하는 가족의 정서적 지지 향상 및 우울증상의 호전을 가져오고, 재입원율의 저하 및 사회재활의 향상을 보이는 것으로 나타났다. Objectives : This study was performed to introduce a psychoeducational family therapy model for the families of schizophrenic patient and to investigate the effect of this model on the changes in coping style and depressive symptoms of the family members, and in perception of emotional support by families and depressive symptoms of patients. Methods : Subjects were schizophrenic out-patients, who fufilled DSM-IV diagnostic criteria, and their families. The members of "education group" were 11 families and patients who participated in more than two thirds of 19 sessions of the program. The members of "non-education group" were 11 families and patients who had no experience of family education and were treated in a general hospital in Pusan. Clinical ratings were performed using by The Ways of Coping Checklist, Family Emotional Support Questionnaire for Transactions, and Beck Depression Inventory. Results : Coping style was changed positively, in education group but not in non-education group. The depressive symptoms of families were decreased in educated group and increased in non-educated group, although there were no statistical significance. In education group, patients felt much better emotional support by their families than patients in non-education group did. At the same time, their depressive symptoms were significantly reduced. The patients from education group were on more successful rehabilitation than those from non-education group were. Conclusion : Our results suggest that this psychoeducational family therapy model would be helpful to induce the positive changes in coping styles and reduce the depressive symptoms of family members, and it could also induce the reduction of depressive symptoms of schizophrenic patients and help their rehabilitation.

항정신병약물을 처음으로 사용하는 초발 정신증 환자에서 나타나는 체중 및 대사성 지표의 변화 : 후향적 연구

김우진,심주철,공보금,강제욱,문정준,김정은,김민걸,박민경,김성진,김현정,정도운 대한생물치료정신의학회 2011 생물치료정신의학 Vol.17 No.2

Objectives:This study was to identify weight & metabolic changes in first-episode psychotic patients with antipsychotics use and investigate the differences of weight & metabolic changes between first-episode psychotic patients and controls with antipsychotics use. Method:In this retrospective study, twenty eight first-episode psychotic patients and twenty eight controls with schizophrenia, schizoaffective or bipolar disorder defined by DSM-IV criteria were included. Information about demographic and clinical characteristics of the subjects was gathered from the medical records. Also body weight, sBP, dBP, fasting glucose, lipid profile and WBC count were evaluated before and after antipsychotics use. Rogistic regression was conducted to assess factors associated with weight gain. Results:First-episode psychotic patients showed more weight and BMI changes than controls after antipsychotics use, and these changes continue over 12 months. On the other hand, there were no significant factors associated with weight gain. Conclusion:The results of present study suggest that antispychotics is one of the major causes inducing weight gain of psychotic patients and antipsychotics-induced weight gain is more vulnerable to drug-naive first-episode psychotic patients.