• 생물정신의학
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• 제12권2호
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• pp.107-113
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• 2005

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.

• 생물정신의학
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• 제4권2호
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• pp.225-233
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• 1997

The authors attempted to examine the allelic association between the A1 allele of Dopamine $D_2$ receptor and schizophrenia, alcoholism, drug addiction in Koreans. Schizophrenic patients(n=31), alcoholism(n=65), drug addiction(n=18) and controls(n=52) were examined by case-control study for distribution of the TaqI polymorphism of the dopamine $D_2$ receptor gene in Korean population to minimize the effect of racial differencies in gene frequencies. In schizophrenics, the numbers of schizophrenics with A1A1, A1A2, A2A2 were 9(29.0%), 15(48.4%) and 7(22.6%) respectively and in alcoholics with A1A1, A1A2, A2A2 were 14(21.5%), 36(55.4%) and 15(23.1%) respectively and in drug addiction with A1A1, A1A2, A2A2 were 2(11.1%), 10(55.6%) and 6(33.3%) respectively and in controls with A1A1, A1A2, A2A2 were 4(7.6%), 24(46.2%) and 24(46.2%) respectively. The prevalence of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 77%, 76.9%, 67% and 53.8% respectively. And the frequency of the A1 allele in schizophrenics, alcoholics, drug addiction and controls were 0.53, 0.49 0.39 and 0.31 respectively. There was significant difference in the frequency of the A1 allele between schizophrenics, alcoholics and controls. We also classified our alcoholic population. For classification by severity, we used the median MAST score 30 in our samples. There was also significant difference in the frequency of the A1 allele between less severe group(0.42) and more severe group(0.57). This data suggest that the A1 allele is associated with schizophrenia and alcoholism in Koreans. Furthermore the prevalence of the A1 allele increassed in more severely affected alcoholics. The authors conclude that our data support an allelic association between the A1 allele at dopamine $D_2$ receptor and schizophrenia, alcoholism. These results suggest the A1 allele of the $DRD_2$ gene is associated with a number of behavior disorders in which it may act as a modifying gene rather than as the primary etiological agent.

• 생물정신의학
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• 제4권1호
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• pp.43-47
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• 1997

The author attempted to examine the allelic association between the A1 allele of Dopamine $D_2$ receptor and alcoholism in Koreans. The allelic distribution of Taq I polymorphism of the $D_2$ dopamine receptor gene with alcoholism was examined in 67 Korean alcoholics and compared with 100 Korean controls. In alcoholics, the numbers of alcoholics with A1A1, A1A2 and A2A2 were 11(16.4%), 30(44.8%) and 26(38.8%) respectively and in controls with A1A1, A1A2 and A2A2 were 17(17.0%), 42(42.0%) and 41(41.0%), respectively. The prevalence of the A1 allele in alcoholics was 61.2% and 59.0% in controls. And the frequency of the A1 allele in alcoholics and controls were 0.39 and 0.38, respectively. There was not significant difference in the frequency of the A1 allele between alcoholics and controls. This data suggest that the A1 allele is not associated with alcoholism in Koreans. The author conclude that our data do not support an allelic association between the A1 allele at Dopamine $D_2$ receptor and alcoholism. Further systemized studies will be necessary to determine whether the role of allele of Dopamine $D_2$receptor is major effect gene or modifying effect gene in the pathogenesis of alcoholism.

• 생물정신의학
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• 제18권2호
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• pp.101-108
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• 2011

Objectives The aim of this study is to explore the association among DRD4 polymorphism, temperament and alcohol drinking behavior of Koreans in their early adulthood. Method Participants were 172 healthy Korean adults (mean age $28.1{\pm}0.8$). Their temperament was assessed with the Temperament and Character Inventory (TCI) and their alcohol drinking behavior were evaluated with a self-reported questionnaire including the CAGE and the Korean version of Alcohol Use Disorder Identification Test (AUDIT-K). DRD4 exon III 48 base pair variable number of tandem repeats (VNTR) was genotyped by PCR. Results No significant association was found between DRD4 polymorphism and TCI temperament dimension (novelty seeking, harm avoidance, reward dependence, and persistence) as well as alcohol drinking behavior scales. However, novelty seeking was significantly associated with alcohol drinking behavior. The higher level of novelty seeking was associated with the higher severity index of drinking (B = -0.225, p < 0.001) and problematic alcohol use on the CAGE and AUDIT-K [Odds Ratio (OR) = 1.111, 95% Confidence Interval (CI) 1.021-1.209, p = 0.015, OR = 1.087, 95% CI 1.009-1.170, p = 0.028]. Conclusion In our study, while there is no significant association of DRD4 polymorphism with temperament and alcohol drinking behavior, novelty seeking affects problematic alcohol use. Results suggest that novelty seeking may play an important role in problematic alcohol use in young Korean adults.

• 생물정신의학
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• 제9권1호
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• pp.15-24
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• 2002

Even though alcoholism is a multi-factorial psychiatric disorder, it is reasonable to suppose that genetic factors play a substantial role in the manifestation of this disorder. Because alcohol is the reinforcing substance which manifests its effects through activation of the mesolimbic dopaminergic reward pathway of the brain, the gene encoding dopamine receptor subtypes can be a major natural candidate gene. Since 1990, many association studies have identified strong evidence implicating the dopamine D2 receptor(DRD2) gene in alcoholism, specifically TaqI A minor(A1) allele. Association studies have also been conducted on other dopamine receptor(DRD3 & DRD4) polymorphisms but the results have yet to be confirmed. Through a number of other approaches, each dopamine receptor gene has been investigated in association with different phenotypes in alcoholism, but further researches will be needed. In conclusion, studies in the past decade have shown that the TaqI A1 allele of the DRD2 gene is associated with alcoholism in various subject groups. Other dopamine receptor genes have since been added to the list but yet to be identified. Thus, the knowledge of these genes and their functional significance will enhance the understanding of the underlying biological mechanisms of alcoholism. Furthermore, it could lead to more helpful prevention and treatment approaches to alcoholism.

• 생물정신의학
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• 제13권4호
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• pp.299-304
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• 2006

Objectives : The purpose of the present study was to investigate whether the TaqI A polymorphism of dopamine receptor D2 gene(DRD2) is associated with Tourette syndrome(TS) and chronic motor tic disorder(CMT) in Korean population. Methods : DRD2 TaqI A RFLP genotyping was carried out with DNA extracted from blood samples of 75 patients with tic disorders(47 with TS and 28 with CMT) and 90 healthy subjects. Genotype and allelic frequencies for the DRD2 gene polymorphisms of the tic disorder group as a whole were compared to those of the control group. Separating the TS group, thereafter, the frequency of genotypes and alleles were compared to those of the controls. Results : The results demonstrated that genotype and allele distributions for the DRD2 gene polymorphism in the tic disorder as a whole, TS, and control groups were not significantly different. Conclusion : No association was found for DRD2 gene, TS and CMT. The data suggest that DRD2 gene may not be a useful marker for the prediction of the susceptibility of tic disorder.

• 생물정신의학
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• 제7권2호
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• pp.152-158
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• 2000

정신분열병과 DRD4 다형성이 연관이 없다는 보고들이 있어왔다. 그러나 지금까지의 결과로부터 정신분열병과 DRD4가 연관이 없다고 결론 내리는 것은 성급한 것일 수도 있다. 정신분열병의 유전적 취약성은 여러 유전자좌(locus)들이 같이 상호작용(interaction) 또는 공작용(coaction)에 의한 것일 가능성이 크다. 저자들은 DRD4 유전자의 exon III 48-염기쌍 다형성 [D4E3]과 exon I 12-염기쌍 다형성[D4E1]의 조합과 정신분열병의 연관성에 관하여 연구하였다. 207명의 친척이 아닌 한국인 정신분열병 환자와 191명의 정상 대조군이 연구에 참여했다. DRD4 유전자형을 중합효소연쇄반응을 통하여 확인하였으며, 정신분열병 환자군과 정상 대조군의 유전자형과 대립유전자의 빈도간의 차이를 연구하였다. 두 군간에 다형성에 있어 통계적 유의한 차이는 보이지 않았으며, 모든 유전자형의 빈도는 Hardy-Weinberg equilibrium에서 예상되는 분포와 유의한 차이가 없었다. 정신분열병 환자군과 정상 대조군에서 DRD4 유전자의 다형성을 조합하여, D4E1과 D4E3 다형성의 조합의 분포에 있어 비교하였을 때, $A1A2^*2/4$의 분포에 있어 두 군간에 유의한 차이가 있었다(p<0.01). 이러한 소견은 D4E1과 D4E3 다형성의 조합중 하나인 $A1A2^*2/4$이 정신분열병의 취약성에 있어 방어적인 역할을 할 가능성을 시사하는 것이다.

• 대한핵의학회지
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• 제39권6호
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• pp.413-420
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• 2005

목적: 수용체 결합능 정량화를 위해서는 방사성추적자의 동태를 충분히 관찰하기 위해서 보통 뇌 PET 영상을 60-120분 정도 얻어야 한다. 이처럼 장기간 PET 영상을 얻게 되는 경우 보통 피험자의 수의적/불수의적 움직임을 피할 수 없고 이러한 피험자의 머리 움직임은 재구성된 PET 영상의 공간해상도를 저하시키고 측정된 방사능 농도의 정확성을 떨어뜨리는 요인이 된다. 이 연구에서는 동적 영상 정보만을 이용하여 피험자의 머리 움직임을 보정할 수 있는 방법을 개발하고 이를 피험자의 움직임이 불가항력적인 뇌활성화 도파민 D2 수용체 영상에 적용하여 움직임 보정이 리간드 결합능 및 외부 자극에 의한 도파민 유리(release) 정량화에 미치는 영향을 평가하였다. 대상 및 방법: 4명의 정상인 자원자에서 비디오 게임에 의한 도파민 유리를 평가하기 위한 실험으로 순간+연속 주입법을 이용하여 얻은 $[^{11}C]raclopride$ PET 영상을 이용하였으며 실제로 도파민 유리를 계산하기 위해서 필요한 프레임들만을 선별해서 영상 정합 기법을 적용하였다. 즉, $[^{11}C]raclopride$을 투여한 후 선조체에서의 리간드의 특이적 결합이 항정상태(steady state)에 최초로 도달하는 과제 수행 전 (30-50 분) 영역과, 비디오 게임 과제에 의해 도파민이 유리된 후 다시 항정상태에 도달하는 70-90분, 비디오 게임을 멈춘 후 다시 항정상태에 도달하는 110-120 분 데이터에만 움직임 보정 기법을 적용하는 방식이다. 각 항정상태 구간은 보통 2-4개의 프레임으로 구성되므로 먼저 이들 프레임들간의 영상정합을 수행(intra-condition registration)하여 평균 영상을 만들고 이들 평균 영상들을 정합하여 최종적으로 움직임 보정(inter-condition registration)을 하였다. 게임 수행 전후의 도파민유리를 평가하기 위하여 머리 움직임 보정 전후의 게임 과제 수행 전후의 결합능 백분율 변화를 구하였으며 각 조건에 대한 결합능 파라미터 영상을 구하고 움직임 보정 전후의 결합능 영상의 화소별 차이를 SPM2를 이용한 t-test(쌍체 검정)로 알아보았다. 결과: 움직임 보정 전후의 영상을 비교하였을 때, 움직임 보정 전 영상에서, 게임 수행시 영상이 게임을 위한 스크린 위치에 따른 시야 변동으로 게임 수행전 영상에 비하여 앞쪽 아래로 기울어져 있음을 알 수 있었으며 이러한 경향은 대상 피험자 모두에서 관찰되었다. 보정 전 영상으로부터 측정된 비디오 게임에 의한 도파민 유리는 putamen에서 29%, caudate head에서 57%, ventral striatum에서 17% 였으나, 보정 후 영상으로부터 구한 도파민 유리는 이들 영역에서 각각 3.9%, 14,1%, 0.6%로 움직임 보정을 하지 않은 경우 선조체 모든 구소물에서 결합능 감소, 즉 게임에 의한 도파민 유리가 과대평가됨을 알 수 있다. SPM 분석결과에서도 움직임을 보정하지 않은 영상을 이용한 경우, 선조체 구조물에서의 결합능 감소와 움직임에 의한 영상강도 저하가 복합적으로 영향을 주어 결합능 차이가 매우 유의하게 평가되었으나 움직임 보정 후 영상을 이용하여 비교한 경우, 결합능 변화가 선조체 영역에서 국한되어 나타나며 그 유의성이 움직임 보정 전에 비하여 낮음을 알 수 있었다. 결론: 뇌활성화 과제 수행시에 동반되는 피험자의 머리 움직임에 의하여 도파민 유리가 과대평가되었으며 이는 이 연구에서 제안한 영상정합을 이용한 움직임 보정기법에 의해서 개선되었다.

• 대한불안의학회지
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• 제4권2호
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• pp.142-147
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• 2008

Objective : Evidence from recent studies supports the role of genetic factors in the development of Posttraumatic Stress Disorder (PTSD). The primary aim of this study is to investigate the association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. The second aim is to examine the association between the DRD2 TaqI A polymorphism and clinical symptoms in patients with PTSD. Methods : We recruited 189 Vietnam veterans for participation in this study, among whom 99 were PTSD patients and 90 were control subjects. The presence of the DRD2 TaqI A polymorphism was determined by polymerase chain reaction (PCR). Several standardized research scales were used in the clinical assessment of PTSD, including the Combat Exposure Scale (CES), Clinician Administered PTSD Scale (CAPS), Beck Depression Inventory (BDI), and Clinical Global Impression (CGI). Results : There was no significant difference in the distribution of the DRD2 genotype, frequency and prevalence of the A1 allele, or the frequency of heterozygotes between the patients with PTSD and the controls. In the PTSD group, the patients with the A1 allele (A1A1, A1A2) scored higher on the CAPS-total (p=0.044), CAPS-avoidance symptoms (p=0.016) and BDI (p=0.024) than those without the A1 allele (A2A2). Conclusion : We could not find an association between the dopamine D2 receptor (DRD2) TaqI A polymorphism and PTSD. However, the A1 allele of DRD2 seemsto influence avoidance symptoms in patients with PTSD.

• 대한불안의학회지
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• 제2권1호
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• pp.45-49
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• 2006

Puropse : Disturbances of dopaminergic system might be related to the possible mechanism of panic disorder. This study was aimed to examine the association of DRD2 Taq 1 polymorphism and panic disorder. Methods : One hundred and fourteen patients with panic disorder (62 male (54.4%), mean age $40.96{\pm}0.11$ years) and 200 comparison subjects (114 male (57.0%), mean age $35.57{\pm}8.81$ years)were tested for DRD2 TaqI A polymorphism. We excluded panic patients with comorbid alcohol related disorders, bipolar disorders, and any kinds of psychotic disorders because there have been some reports about association of these disease and DRD2 TaqI A polymorphism. Results : There was significant difference in the frequency of the genotype in DRD2 polymorphism between patients and controls (${\chi}^2$=6.09, df=2, p=0.048). The A1+ allele (A1A1 and A1A2) frequency analysis also showed significant association (${\chi}^2$=4.08, df=1, p=0.043). In addition, we observed a more strong and specific association between panic disorder and the A1+ allele of the DRD2 TaqI polymorphism for men (${\chi}^2$=4.71, df=1, p=0.03), but not for women (${\chi}^2$=0.45, df=1, p=0.50). Conclusion : These results in our Korean sample suggest that the DRD2 TaqI A polymorphism may be associated with panic disorder. Furthermore, we found sex-specific association of DRD2 A1 allele with panic disorder.