• 생물정신의학
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• 제25권1호
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• pp.16-20
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• 2018

Objectives Psychological resilience is the ability to cope with stress. The genetic background behind psychological resilience is not much known. The serotonin transporter and dopamine transporter are implicated in stress related psychology and emotional processing. The aim of this study is to investigate a possible genetic role of functional polymorphisms of serotonin and dopamine transporters for psychological resilience. Methods A total of 951 healthy adult subjects were included. Psychological resilience was measured using Connor-Davidson Resilience Scale (CD-RISC). Genotyping was performed for serotonin transporter gene(SERT) promoter variable number tandem repeat (VNTR) and dopamine transporter gene(DAT1) 3'-untranslated region (UTR) VNTR. Genetic association analysis was conducted between genotypes and the CD-RISC score. Results No genetic association was observed for SERT promoter VNTR or DAT1 3'-UTR VNTR with CD-RISC score. No genetic interaction between SERT promoter VNTR and DAT1 3'-UTR VNTR with CD-RISC score was detected. Conclusions Either serotonin or dopamine transporter did not seem to play a significant role for psychological resilience in this sample.

• 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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• 제17권2호
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• pp.65-69
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• 2010

Gene-environment interactions are important in pathogenesis of suicide or suicidal behavior. Twin and adoption studies and family studies show that genetic factors play a critical role in suicide or suicidal behavior. Given the strong association between serotonergic neurotransmission and suicide, recent molecular genetic studies have focused on polymorphisms of serotonin genes, especially on serotonin transporter and tryptophan hydroxylase genes. Some studies have revealed a significant interaction between s allele of the serotonin transporter gene and the risk of suicide attempt associated with childhood trauma. In addition, the polymorphism of brain-derived neurotrophic factor gene also may influence the effect of childhood trauma in relation to the risk of attempting suicide. Future studies should explore genetic and environmental factors in suicide or suicidal behavior and examine for gene and environment interaction.

• 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.

• 생물정신의학
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• 제9권1호
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• pp.34-41
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• 2002

Background:Since serotonin neurotrasnmission plays an important role in the pathophysiology of depression, the drug that acts on serotonin transporter can be an effective antidepressant. The aim of this study was to investigate the relationship between serotonin transporter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. Method:The 175 depressive patients, who met DSM-IV criteria for major depressive disorder or dysthymic disorder were enrolled into three year study. The genotypes of the patients were investigated by polymerase chain reaction of genomic DNA with promoter regions of the serotonin transporter gene. The patients were assessed by the Clinical Global Impression Scale, at the 1st visit, 8th week, 16th week, 1st year, 2nd and 3rd year after the antidepressant treatment. Result:The genotypes of 138 patients were investigated and 128 of them finished this 1st year study and 107 remained in the study after 2-year treatment, and, 97 completed this 3-year study. The therapeutic response of each subset was not different at 8th, 16th week, but the subset with homozygote(l/l) of long variant showed a better antidepressant therapeutic response than heterozygote(l/s). The heterozygote(l/s) showed a better response than the subset with homozygote(s/s) of short variant at 1st, 2nd and 3rd year after the antidepressant treatment in CGI-global improvement score. Conclusion:This result shows that the serotonin transporter polymorphism may be related to the long-term effect of antidepressant treatment and there may be also ethnic difference.

• 생명과학회지
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• 제20권10호
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• pp.1451-1457
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• 2010

Serotonin (5-hydroxytryptamine (5-HT))는 신경계의 세포-세포 간의 신호전달의 주요한 신경전달물질이다. 세포막에 존재하는 serotonin transporter (SERT)는 연접간격에 존재하는 5-HT를 세포 내로 재흡수 하여 세포외부의 5-HT 농도를 조절하지만 그 기전은 아직 밝혀지지 않았다. 본 연구에서는 yeast two-hybrid system을 사용하여 SERT의 C-말단이 protein kinase C-$\varepsilon$ (PKC-$\varepsilon$)과 특이적으로 결합함을 알았다. PKC-$\varepsilon$는 PKC의 isotype으로 calcium 비의존적이며 phorbol ester/diacylglycerol 민감성 serine/threonine kinase이다. $Na^+/Cl^-$ 의존성 SLC6 gene family의 다른 수송체는 PKC-$\varepsilon$과 결합하지 않았다. Deletion mutant들을 사용하여 SERT는 PKC-$\varepsilon$의 C-말단부위와 결합함을 알았으며, 또한 이 단백질간의 결합을 GST pull-down assay로 확인하였다. PKC-$\varepsilon$는 in vitro에서 SERT의 N-말단의 펩티드를 인산화시켰다. 이러한 결과들은 PKC-$\varepsilon$에 의한 SERT의 인산화가 세포막에 존재하는 SERT의 활성을 조절하는 역할을 할 가능성을 시사한다.

• Journal of Acupuncture Research
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• 제19권1호
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• pp.111-117
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• 2002

목적 : 본 연구는 serotonin transporter (5-HTT) 유전자다형성이 중풍의 발병과 관련이 있는지 알아보기 위해 수행하였다. 대상 : 경희의료원 한방병원에 입원한 중풍환자 139명과 각 병원 중풍 기왕력이 없는 건강인 138명을 대상으로 하였다. 방법 : 각 그룹에서 개개인마다 DNA를 분리 정제한 후 Taq polymerase로 증폭하여 한천 겔에서 전기영동을 하여 잘려진 DNA fragment의 양상을 관찰하였다. 결과 : L/L, L/S, S/S의 세가지 유전자형이 검출되었으며 중풍군과 대조군 사이에 유의성 있는 차이는 발견되지 않았다. 개별 allele 빈도에 있어 중풍군과 건강인 사이에는 통계적인 유의성이 나타나지 않았다. 결론 : 이상의 결과를 통하여 5-HTT 유전자다형성은 중풍의 발병과는 직접적인 관련이 없는 것으로 사려되며 더 많은 환자를 대상으로 다른 환경요인 또는 유전자와 연관성에 대한 심도깊은 연구가 필요하다고 하겠다.

• 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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• 제11권2호
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• pp.136-145
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• 2004

Objectives:Genetic variations of the tryptophan hydroxylase(TPH) gene and the serotonin transporter linked polymorphic region(5-HTTLPR) polymorphism have been associated with its functional capacity. The authors investigated whether the allelic constitution of the TPH gene and 5-HTTLPR are associated in Korean panic patients. Methods:244 Korean patients with panic disorder and 227 normal healthy controls were tested for a genetic polymorphism of TPH A218C and 5-HTTLPR polymorphism. To assess the severity of panic disorder during the last one month, anticipatory anxiety, panic difficulty, panic distress, agoraphobic difficulty and agoraphobic distress were measured with visual analogue scale(VAS) score, STAI-S & T, BDI, SCL-90-R, ASI-R, CGI, PDSS, and HAMD. Results:There was no significant difference in genotype and allele frequencies of TPH A218C and 5-HTTLPR polymorphism between panic patients and controls. Although we observed some differences in genotype and allele frequencies of TPH A218C polymorphism among male subjects, these differences disappeared after Bonferroni correction. And there were no significant differences in clinical variables. Conclusion:Our results suggested that there are no association between the genetic polymorphism of TPH gene and 5-HTTLPR with panic disorder.

• 생물정신의학
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• 제16권2호
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• pp.121-126
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• 2009

Objectives : The serotonin transporter gene(SLC6A4) is one of the most widely studied candidate genes in autism spectrum disorder(ASD), but there have been conflicting results from studies into the association between SLC6A4 and ASD. The aim of this study was to evaluate the association between single nucleotide polymorphisms(SNPs) in the SLC6A4 gene and ASD in the Korean population. Methods : We selected 12 SNPs in SLC6A4 and observed the genotype of 151 Korean ASD trios. We tested the family-based association for each individual polymorphism and haplotype by using the standard TDT method in Haploview(http://www.broad.mit.edu/mpg/haploview/). Results : Through transmission-disequilibrium testing and haplotype analysis, we could not find any statistically significant transmitted allele or haplotype. In addition, a case-control association test with Korean HapMap data did not reveal any statistical significance. Conclusion : Although serotonin-related genes must be considered candidate genes for ASD, we suggest that common SNPs of SLC6A4 are not important markers for associations with Korean ASD.