• Korean Journal of Biological Psychiatry
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• v.23 no.4
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• pp.166-172
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• 2016

Objectives We investigated whether the catechol-O-methyltransferase (COMT) and serotonin related gene polymorphisms may be associated with agoraphobia in patients with panic disorder in Korea. Methods The COMT gene (rs4680), 5-hydroxytryptamine (serotonin) transporter linked polymorphic region (5-HTTLPR) gene (rs25531), serotonin receptor 1A (HTR1A) gene (rs6295) genotypes were analyzed in 406 patients with panic disorder and age-sex matched 206 healthy controls. Patients with panic disorder were dichotomized by the presence of agoraphobia. The following instruments were applied : the Beck Depression Inventory, the Beck Anxiety Inventory, the Panic Disorder Severity Scale. Results There was a significant difference in the distribution of 5-HTTLPR genotype between panic patients with agoraphobia and without agoraphobia (p = 0.024). That is, the panic patients with agoraphobia had a significant excess of the less active 5-HTTLPR allele (S allele). (p = 0.039) Also, we replicated previous western reports which indicated a significant difference in the distribution of COMT genotype between the patients with panic disorder and the healthy controls (p = 0.040). However, no significant associations of agora-phobia or panic disorder with HTR1A gene polymorphisms were found. Conclusions This result supports that the COMT polymorphisms may be associated with panic disorder and suggests that the 5-HTTLPR polymorphisms may play a role in the pathogenesis of agoraphobia in the Korean patients with panic disorder.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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• pp.88-93
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• 2004

Background:Serotonin transporter gene-linked polymorphism region(5-HTTLPR) and catechol-O-methyltransferase( COMT) genes are thought to be important factors in some personality traits and the etiology of anxiety disorder. The goal of this study was to determine the role of these genes in personality traits. Method:The participants included 116 healthy adults with no history of psychiatric disorders and other physical illness for the last 6 months. All participants were tested by Temperament and Character Inventory(TCI). The 5-HTTLPR, COMT val158met gene polymorphisms were analyzed with PCR(Polymerase Chain Reaction). Differences on TCI dimensions and sub-scales among groups were examined with t-test and ANOVA. Result:There were possible relationships of the 5-HTTLPR with self-transcendence(P=0.050) and COMT val158met polymorphism with cooperativeness(P=0.053). Conclusion:We found associations between 5-HTTLPR, COMT polymorphisms and the some TCI character dimensions. Further studies of polymorphisms of other genes and their interactions may clarify the complex relationship between personality and genes.

• Korean Journal of Biological Psychiatry
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• v.14 no.4
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• pp.268-273
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• 2007

Objectives : Findings from behavioral genetics which demonstrate the high heritability of personality traits have stimulated the search for the specific genes underlying personality. A large number of association studies have investigated a correlation between serotonin transporter-linked promoter region(5-HTTLPR) polymorphism and personality traits but the results have been inconsistent. So, the aim of this study is to investigate in a large sample with homogenous background about ethnicity, gender, occupation, and age. Methods : The participants included 247 healthy Korean female adults(mean age=23.12, SD=3.22)with no history of psychiatric disorders and other physical illnesses. Genomic DNA was extracted from peripheral blood, and genotyping was performed by PCR. Personality assessment was done with the Temperament and Character Inventory(TCI). Results : Genotype Frequencies are l/l 3.6%, l/s 32.8% and s/s 63.6%(l allele:20%, s allele:80%). This low frequency of the l allele and l/l genotype was different from Caucasian results. No significant association was observed between 5-HTTLPR polymorphism and personality traits in a Korean female population. Conclusions : This study investigated the association between 5-HTTLPR polymorphism and personality traits in Korean female subjects, a large sample with homogeneous background about ethnicity, gender, occupation, and age. No significant association was observed between 5-HTTLPR polymorphism and personality traits in a Korean female population.

• Korean Journal of Biological Psychiatry
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• v.25 no.3
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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.

• Korean Journal of Biological Psychiatry
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• v.10 no.2
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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.

• Korean Journal of Biological Psychiatry
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• v.13 no.3
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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.

• Korean Journal of Biological Psychiatry
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• v.11 no.2
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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.

• Korean Journal of Biological Psychiatry
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• v.9 no.1
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• pp.25-33
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• 2002

Serotonin transporter(5-HTT) is one of the major action site of antidepressants in neuronal cells. According to the recent studies, it is known that the functional polymorphism in the promoter region of the 5-HTT gene(5-HTT linked polymorphism repetitive element in promoter region, 5-HTTLPR) is associated with antidepressant responsiveness, and the distributions of 5-HTTLPR is various among the different populations. Our preliminary study suggested that it is possible to measure the endophenotype of 5-HTTLPR genotype by examining the pharmacodynamic research of the 5-HTT in platelet membranes. However, there are limitations to predicting the antidepressant responsiveness only from the endophenotypic characteristics of 5-HTT gene promoter polymorphism, and therefore we propose to use the pharmacogenomic methods for overcoming these limitations. We found that the significant correlations existed among the genetic polymorphisms of biogenic amine transporters whose structure and characteristics are similar to the 5-HTT, and the predictable odds ratio of antidepressant responsiveness are increased significantly by combining the effect with other associated polymorphisms, compared to the effect of 5-HTT promoter polymorphism only. These results support the hypothesis that antidepressant treatment has to be individualized according to the genetic and ethnic background of depressed patients. It would be possible to develope the evaluation tools to predict the antidepressant responsiveness and its side effect profile, if scientists reveal the genes related to the action mechanism as well as the metabolism of antidepressants so as to discover the interaction of those genes and contribution of endogenotypes toward antidepressant responsiveness.

• Korean Journal of Biological Psychiatry
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• v.11 no.1
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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.

• Korean Journal of Biological Psychiatry
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• v.9 no.1
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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.