• 생물정신의학
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• 제9권1호
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• pp.25-33
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• 2002

우울증 환자들에게 항우울제를 처방하는 임상의들이 흔히 겪게 되는 두 가지 어려움은 약물의 치료 반응 유무를 판단하기 위하여 처음 약물을 투여한 후 4~6주 이상을 기다려야 하는 것과 어떤 종류의 항우울제라도 처음 4~6주 이후에도 반응을 보이지 않는 환자들이 30~40% 이상이 된다는 것이다. 이와 같은 어려움을 극복하기 위해서는 환자 개개인의 항우울제에 대한 반응성을 미리 예측하는 것이 필요하다. 이 논문에서는 연구자들의 과거 실험들과 이미 발표된 연구들을 중심으로 하여 항우울제에 대한 치료 반응성을 예측하는데 약리유전학적 방법을 이용한 현재까지의 연구들과 연구 결과를 해석 할때 고려해야 할 사항을 살펴보고자 한다. 세로토닌 수송체(serotonin transporter, 5-HTT)는 항우울제가 신경세포에 작용하는 주요 작용부위 중 하나이다. 최근의 연구들에 의하면 5-HTT 유전자 promoter 부위의 기능적인 다형성(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR)이 항우울제에 대한 치료 반응성과 관련이 있는 것으로 알려져 있으며, 5-HTTLPR 유전형의 분포빈도는 인종들 간에서 차이가 있는 것으로 알려져 있다. 연구자들은 최근의 실험을 통하여 5-HTTLPR 유전형들의 endophenotype을 혈소판 막에 분포하는 5-HTT의 약동학적 특성으로 측정할 수 있음을 발견하였다. 흥미로운 사실은 5-HTTLPR 유전형의 분포가 인종적으로 다른 양상으로 나타났듯이, 그 endophenotype인 혈소판막의 5-HTT의 약동학적 특성 역시 전혀 반대되는 양상으로 나타났다. 하지만 이 endophenotype의 특성만으로 항우울제의 치료반응을 예측하는 것은 아직까지 한계가 있으며, 향후 이러한 과제를 해결하기 위한 방법중 약리유전학적 방법을 사용할 수 있음을 제안하였다. 예비적으로 시행한 실험을 통하여 연구자들은 세로토닌 수송체의 구조와 특징이 비슷한 생체아민 수송체들의 유전자 다형성들 간에 유의한 상관관계가 있음을 발견하였으며, 이들 유의한 상관관계가 있는 유전자형을 연합하여 조합할 때 세로토닌 수송체의 유전형만의 기여도보다도 항우울제에 대한 반응 예측도의 odds ratio가 유의하게 상승함을 발견하였다. 이러한 연구 결과들은 임상의가 항우울제를 처방 할 때에 환자들의 유전적 그리고 인종적인 배경을 고려하여 개별화된 전략을 사용하여야 한다는 가설을 뒷받침한다. 앞으로 항우울제의 작용기전과 그 대사과정에 관여하는 유전자들들 중심으로 유전자 간의 상호 작용을 밝히고 그 표현형이 약물의 치료 반응도에 미치는 기여도를 평가하는 작업들은 항우울제의 치료 반응과 그 부작용을 미리 예측할 수 있는 평가 도구를 개발할 수 있는 가장 최선의 길이 될 수 있을 것이다.

• 생물정신의학
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• 제10권2호
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• pp.159-167
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• 2003

Objective:Under the hypothesis that 5-HTTLPR polymorphism plays some role in the susceptibility or vulnerability of some subgroup of alcohol dependence, associations of 5-HTTLPR polymorphism with alcohol dependence were examined. Method:This association analysis included 109 Korean alcohol dependent and 113 Korean control subjects. DNA of all subjects were genotyped for the biallelic functional polymorphism in the 5-HTTLPR. Considering the likelihood of heterogeneity in the alcohol dependence phenotype, alcohol dependent subjects were subgrouped by onset age, family history of alcohol dependence and severity of withdrawal symptoms. Results:There were no significant differences in the frequencies of either the 5-HTTLPR genotype or the short vs. long allele in alcohol dependent and control subjects. The frequency of the S allele and S-carrier (LS or SS genotype) was significantly increased in the early onset alcohol dependent subjects and the familial alcohol dependent subjects compared with that in the control subjects. Conclusion:The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased susceptibility or vulnerability to develop early onset alcohol dependence and familial alcohol dependence, which characterize Cloninger's type 2 alcohol dependence.

• 생물정신의학
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• 제13권3호
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• pp.170-177
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• 2006

Objectives : Disturbances of serotonergic system might be related to the possible mechanism of social phobia. This study was to investigate the association of serotonin transporter gene and social phobia. Methods : Sixty nine patients with social phobia(51 male(73.9%), mean age $35.17{\pm}11.89$ years) and seventy four normal controls(54 male(73.0%), mean age $33.46{\pm}9.63$ years) were tested for serotonin transporter gene-linked polymorphic region(5-HTTLPR) polymorphism. Additionally, patients were grouped into 46 generalized(GEN) and 23 nongeneralized(NGEN) subgroups and 5-HTTLPR polymorphism was compared with that of normal controls. The genotypes and allele frequencies of the 5-HTTLPR polymorphism between social phobia and the control group were compared. Genomic DNA was extracted from their blood and 5-HTTLPR polymorphisms were determined by using polymerase chain reaction. Results : Significant association was observed between the S(ss) genotype and social phobia, by functional classification(p=.010). In allele frequency analysis, a significant association was also observed between the short allele and social phobia(p=.030). A significant associations between S genotype and each subgroup were observed(GEN p=.045 ; NGEN p=.033), but there were no differences in allele frequency. And, no differences in genotype and allele distribution between two subgroups were found. Conclusion : The results in our Korean sample suggest that S genotype of 5-HTTLPR may be associated with social phobia and s allele may be an important genetic factor that activates social phobic symptoms. But, further studies including large number of samples are necessary to elucidate these present findings.

• 생물정신의학
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• 제8권2호
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• pp.220-225
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• 2001

As numbers of serotonin's function are so many, studies of serotonin are numerous nowadays. In the beginning, concentration of metabolites such as 5-HIAA was a key issue, but recent studies have been challenged for serotonin receptor genes and their relation to mood disoder. Serotonin transporter(5-HTT) gene is a strong candidate gene of mood disoder for following reason. Serotonin transporter is a key protein in the serotonin pathway as it regulate the concentration of serotonin in the synaptic clept and essential pathophysiology of depression is dysregulation of 5-HTT so that all antidepressants have effect of 5-HTT antagonist. The decrease of 5-HTT in the platelet and in brain of the depressive patients is much consistent results in the studies of the pathophysiology of mood disorder till now. By this, we will be able to develop simple and easy marker for diagnosis, type, and treatment monitoring of depression. Many psychiatrists have sought the independent genes in relation to depression or schizophrenia. Obviously, the hereditary vulnerability contributes to etiology of mood disorders, but it is difficult to discriminate the independent genes because of many environmental factors. Moreover, in the hereditarily complex diseases such as mood disorder, the only vulnerability of gene can not sufficiently explain the etiology. In the future, to exclude the role of the gene-environmental interaction, the methods such as gene transfer can be considered. In the opposite direction, by using the gene destruction method, the role of target genes can be examined. As yet the concept of the gene expression, neural plasticity, neurogenesis and etc, is the elementary stage. The development of this field will help to establish the treatment strategy of chronic and refractory mood disorders.

• 생물정신의학
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• 제19권2호
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• pp.106-113
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• 2012

Objectives : The purpose of this study is to investigate the relationship between the triallelic serotonin transporter gene and stressful life events to determine their effect on depression with alcohol dependence. Methods : Ninety-five hospitalized patients with alcohol dependence (73 male, 22 female) were enrolled in this study. Thirty-two (33.7%) of the total patients were diagnosed with major depressive disorder and dysthymic disorder by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-IV. The characteristics of stress were evaluated using the stressful life events scale, and depressive symptoms were assessed using the depression scale (Beck Depression Inventory, BDI). Alcoholism with depression (n = 32) and alcoholism without depression (n = 63) were genotyped for the triallelic serotonin transporter gene ($L_A$ : higher expressing allele, $L_G$/S : lower expressing allele). Results : There was no significant difference in the allele frequency between the depression group and the non-depression group (${\chi}^2$ = 0.345, p = 0.619). $L_G$/S alleles had more comorbid depression in the higher score of stressful life events scale [Mental-Haenszel (MH)-${\chi}^2$ = 4.477, p = 0.034]. But there was no significant difference in the comorbidity according to the scores from the stressful life event scale in the $L_A$ alleles (MH-${\chi}^2$ = 0.741, p = 0.399). In the results, alcohol-dependent individuals with $L_G$/S alleles had more comorbid depression than those with $L_A$ alleles when they had experienced severe stressful life events (MH-odds ratio = 2.699, p = 0.028). Conclusions : These results suggest that there is no direct relationship between triallelic serotonin transporter gene and depression in the alcohol dependent patients. But alcohol dependent individuals with the lower expressing alleles of the serotonin transporter gene were more susceptible to depression than those with the higher expressing alleles in response to stressful life events.

• 정신신체의학
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• 제16권1호
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• pp.47-51
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• 2008

연구목적 : 최근 세로토닌-노르에피네프린차단제가 공황장애를 비롯한 불안장애에 효과가 있음이 알려지면서 불안증상의 발생에 있어서 노르에피네프린의 역할에 대한 관심이 늘어나고 있다. 본 연구는 노르에피네프린 수송체 T182C유전자 다형성과 불안관련특질의 연관여부를 탐색하고자 하였다. 방법 : 169명의 여고생을 대상으로 노르에피네프린 T182C유전자 다형성을 조사하였다. 불안관련특질과의 연관 여부를 확인하기 위해 불안민감성척도와 스필버그 상태-특성 불안척도의 특성불안척도를 작성하게 하여 유전자형에 따른 점수의 차이여부를 비교하였다. 결과 : 피험자는 전원여성으로 평균연령은 $16.73{\pm}0.7$세였다. 유전자 분석결과 TT형은 106명, TC형은 55명, CC형은 8명이였으며 이는 Hardy-Weinberg평형에 위배되지 않았다. 노르에피네프린 T182C유전자형에 따른 불안민감성의 차이는 관찰되지 않았다. 불안민감성척도의 하위척도와 특성불안척도에 대한 분석에서도 통계적으로 의미있는 차이는 관찰되지 않았다. C 대립유전자 보유여부에 따라 동일한 비교를 수행하였을 때 에도 유의한 차이는 나타나지 않았다. 결론 : 저자들의 연구에서는 노르에피네프린 수송체 T182C유전자 다형성과 불안민감성척도를 사용해 측정한 불안민감성 및 스필버그 상태-특성 불안척도를 사용하여 측정한 특성불안간의 유의한 연관을 관찰할 수 없었다.

• 생물정신의학
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• 제16권1호
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• pp.25-36
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• 2009

Objectives : The aim of this study was to investigate the association between Korean ADHD patients and the l/s polymorphism of serotonin transporter(5-HTTLPR). Methods : The study sample consisted of 189 Korean ADHD children diagnosed by Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Version-Korean Version(K-SADS-PL), both parents of ADHD children, and 150 normal children. DNA were extracted from the blood of all samples, and genotyping was done. Based on the allele and genotype information, not only the case-control analysis between ADHD and normal children but also the family-based association test among ADHD children and their parents. Transmission disequilibrium test(TDT) were performed for family-based associated test(number of trio=113). The results of the clinical rating and neuropsychological tests were compared according to the l/s genotype of ADHD children. Results : In case-control analysis, there were no statistically significant difference of l/s gene polymorphism between ADHD and normal children in various kinds of analysis condition. In family-based association study, TDT failed to detect linkage disequilibrium between l/s gene polymorphism and ADHD in whole ADHD families. However, in the families of ADHD inattentive type only(number of trio=23), I allele was transmitted more preferentially in the proband with ADHD even if the number of families was small(${\chi}^2$=4.57, p=.032). In the analysis of the results from the clinical scales and neuropsychological tests in ADHD children, the score of the Novelty- Seeking of ADHD children with l/l genotype was significantly lower than with the other genotypes(F=3.15, p=.047), and that of Self Transcendence was significantly higher(F=4.25, p=.017). Conclusion : The results of this study suggest there were no significant genetic association between the 5- HTTLPR gene polymorphism and Korean ADHD.

• 생물정신의학
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• 제25권3호
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• pp.79-87
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• 2018

Objectives Internet gaming disorder (IGD) is known to be related to stress and the serotonin-transporter-linked polymorphic region (5-HTTLPR) that is known to be associated with stress and has been studied to affect various psychiatric illness outbreaks. We tried to examine the relationship between stress, 5-HTTLPR and IGD. Methods A total of 59 participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria and 67 normal controls (NC) were enrolled. The IGD group and the NC were compared using chisquare test and independent sample t-test, and logistic regression analysis was used to examine the relationship between stress, the 5-HTTLPR, and IGD. Results The mean scores for anxiety, impulsivity and stress were significantly higher in the IGD group than in the NC. In addition, there was a significant association between stress and IGD [odds ratio (OR) = 1.172, 95% confidence interval (CI) = 1.008-1.362]. Conclusions This study showed that stress would affect IGD. Therefore, the evaluation and management of stress should be included in the diagnosis and treatment of IGD.

• 생물정신의학
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• 제11권1호
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• pp.49-53
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• 2004

Objective:A Comparison of QTc prolongation for various antipsychotics and an analysis of QTc prolongation for the various types of serotonin transporter polymorphism were performed. Method:EKG was checked, followed by QTc measurement as Bazett's correction, and the serotonin transporter polymorphism was examined in 110 chronic schizophrenia patients were performed EKG before 24 weeks ago. We defiened QTc prolongation as over 450ms. The risk factor of sudden cardiac death were defiend as QTc prolongation and or 60ms in delta value. Result:The prevalence of QTc prolongation in this study was 7.3%, and the prevalence of over 60ms was 4.5%. Patients who had the risk factors were 10(9.1%). 6/52 who prescribed atypical antipsychotics and 2/58 who prescribed haloperidol showed QTc prolongation. The prevalence who had the risk factor of sudden cardiac death were 16% in atypical antipsychotics group, 3.4% in haloperidol group. QTc prolongation were observed more frequently in l/l type than s/s type. l allele frequency were 50% in QTc prolongated group, 19% in not prolongated group. l allele had an association with QTc prolongation(p<0.01). Conclusion:The prevalence of QTc prolongatin was frequent in chronic schizophrenia patients who were prescribed atypical antipsychotics. It has strong association with l allele of 5-HTTLPR.