• Korean Journal of Biological Psychiatry
• /
• v.23 no.4
• /
• pp.166-172
• /
• 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
• /
• v.11 no.2
• /
• pp.88-93
• /
• 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
• /
• v.13 no.3
• /
• pp.170-177
• /
• 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
• /
• v.11 no.2
• /
• pp.136-145
• /
• 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
• /
• v.10 no.2
• /
• pp.159-167
• /
• 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.

• Molecular & Cellular Toxicology
• /
• v.4 no.1
• /
• pp.1-4
• /
• 2008

The 5-HTT gene is a candidate gene for influencing the clinical response to antidepressant treatment. The purpose of this gene study was to determine the relationship between serotonin transporter gene polymorphism at the SLC6A4 and the response to citalopram in a Korean population with major depressive disorder (MDD). Citalopram was administered for 8 weeks to the 80 patients who completed this study. The severity of depression was assessed with the 21-item Hamilton Depression Rating scale, and the 5-HTTLPR genotypes in the patients were determined using the polymerase chain reaction. Our result did not showed significant differences in, allele, and carrier distribution between the normal group and MDD patients. This study suggest that polymorphism of the 5HTT gene was not associated with citalopram response to MDD in the Korean population.

• Korean Journal of Biological Psychiatry
• /
• v.9 no.1
• /
• pp.25-33
• /
• 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
• /
• v.9 no.1
• /
• pp.34-41
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.16 no.1
• /
• pp.25-36
• /
• 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.

• Korean Journal of Biological Psychiatry
• /
• v.8 no.2
• /
• pp.226-232
• /
• 2001

The pharmacotherapy of depression has reduced morbidity and improved outcome for many depressive patients. A wide range of classical and new antidepressants are available for their treatment. However, 30-40% of all patients do not respond sufficiently to the initial treatment and present adverse effects. Pharmacogenetics studies the genetic basis of an individual's ability to respond to pharmacotherapy. Recently, some reports on serotonin transporter gene polymorphisms and their influence on the response to antidepressive therapy provide an interesting diagnostic tool in assessing the chances of response to antidepressants. We also investigated the relationship between serotonin transprter polymorphisms(5-HTTLPR) and the long-term effect of the antidepressant treatment. 128 depressive patients were enrolled into 2nd 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 therapeutic response to antidepressant than the heterozygote(l/s) of long and short variant, which showed a better therapeutic response than the subset with homozygote (s/s) of short variant at 1st year and 2nd year after the antidepressant treatment. This result shows that the serotonin transporter polymorphisms may be related to the long-term effect of antidepressant treatment. The potential for pharmacogenomics, the use of genetic information to guide pharmacotherapy and improve outcome by providing individualized treatment decisions, has gained increasing attention. pharmacogenomics will contribute to individualize drug choice by using genotype to predict positive clinical outcomes, adverse reactions, and levels of drug metabolism. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual molecular profile, will impact the antidepressant therapy and this approach will replace the traditional trial-and-error practice of medicine.