The 5-HT2A receptor is of great interest for research into schizophrenia and psychopharmacology in light of the observation that schizophrenic patients has 5-HT cortical-subcortical imbalance and atypical antipsychotic clozpine has 5-HT2A antagonists properties. An significant association between schizophrenia and the T102C polymorphism of the gene for 5-HT2A receptor has been reported. In this study, we investigated an association between schizophrenia and the T102C polymorphism of the gene for 5-HT2A receptor in Korean schizophrenic patients. The subjects consisted of 139 schizophrenic patients and 88 normal controls. Genomic DNA was amplified by PCR and digested with MsPI. The uncutt product identified allele 1(nucleotide sequence TCT) ; digested products of 216bp and 156bp identified allele 2(nucleotide sequence TCC). The allele frequencies and the genotypic distribution of 5-HT2A receptor gene were not significantly different between schizophrenic patients and normal controls. Since allele frequencies of the T102C polymorphism may differ between individuals of different ethnic backgrounds, it needs to be conducted in an advanced research.
Alleles ; DNA ; Gene Frequency ; Humans ; Polymerase Chain Reaction ; Psychopharmacology ; Receptor, Serotonin, 5-HT2A ; Schizophrenia* ; Serotonin ; Serotonin 5-HT2 Receptor Antagonists

OBJECTIVES: Recently, polymorphisms of several serotonin genes have been suggested to be associated with suicide, but the results are still unclear. We examined whether the T102C polymorphisms of the serotonin 2A receptor gene and the G861C polymorphisms of the serotonin 1B receptor gene were associated with suicidal behavior using drug intoxication. METHODS: The subjects were 52 patients who visited emergency room with suicidal behaviors. Fifty controls were selected from healthy volunteers matched for sex and age to the suicide subjects. The polymorphisms were analyzed with TaqMan(R) assay using primers based on previous studies. RESULTS: The T102C polymorphism of the serotonin 2A receptor gene showed no significant difference between the suicidal attempters and controls in both genotype and allele frequency analyses(p=0.179 and p=0.422, respectively). There was no statistically significant difference between the suicidal attempters and the controls in the G861C polymorphism of the serotonin 1B receptor gene and any significant effect of the genotype distributions or the allele frequencies was not observed(p=0.092 and p=0.987, respectively). CONCLUSION: These findings suggest that the T102C polymorphism in serotonin 2A receptor gene and the G861C polymorphism in serotonin 1B receptor gene are not related to the susceptibility to suicide attempts using drugs. To clarify the genetic influences of the serotonergic system on suicidal behavior, the polymorphisms of other candidate genes in the serotonergic system should be studied with larger numbers of subjects.
Emergency Service, Hospital ; Gene Frequency ; Genotype ; Healthy Volunteers ; Humans ; Receptor, Serotonin, 5-HT1B ; Receptor, Serotonin, 5-HT2A ; Serotonin* ; Suicide

Many neurotransmitters other than dopamine, such as serotonin, glutamate, etc, have been implicated in the pathophysiology of schizophrenia. The atypicality of new antipsychotics has been attributed to the relatively more potent 5-HT2A receptor antagonism compared to D2 receptor blocking action. However, dopamine still seems to be a cornerstone in terms of the pathophysiology of schizophrenia and mode of action of antipsychotics. Therefore, we reviewed all the relevant papers about the dopamine hypotheses for schizophrenia and reclassified into 3categories: 1) Regional classification of dopamine hypothesis ; 2) Dopamine gating (filtering) hypothesis ; and 3) Time-course classification of dopamine hypotheis. How they are developed and the implications of each hypothesis will be described in detail. In the future, dopamine hypothesis at molecular or cellular levels will be investigated more extensively though its current status is very primitive.
Antipsychotic Agents ; Classification ; Dopamine* ; Glutamic Acid ; Neurotransmitter Agents ; Receptor, Serotonin, 5-HT2A ; Schizophrenia* ; Serotonin

OBJECTIVES: This study was designed to investigate the association between 5-HT 2A receptor gene promoter -1438A/G polymorphism and bipolar disorder in a Korean population. METHOD: 5-HT2A receptor gene promoter -1438A/G polymorphism were typed with Polymerase Chain Reaction in 120 patients with bipolar disorder and 120 normal controls. RESULT: The distributions of the genotype in the bipolar disorder with A/A, A/G, G/G were 14 (12%), 66(55%), 40(33%), and in the controls were 30(25%), 59(49%), and 31(26%). The allele frequencies of the bipolar disorders with A and G were 94(39.2%), 146(60.8%), and in the controls were 119(49.6), and 121(50.4), respectively. There were significant differences in genotype distributions and allele frequencies of -1438A/G between patients with bipolar disorder and normal controls. CONCLUSION: These results suggest that 5-HT2A receptor gene promoter -1438A/G polymorphism may be related to the development of bipolar disorder in a Korean population.
Bipolar Disorder* ; Gene Frequency ; Genotype ; Humans ; Polymerase Chain Reaction ; Receptor, Serotonin, 5-HT2A* ; Serotonin

Blonanserin is a newly developed agent which is approved for the treatment of schizophrenia in Japan and Korea. This agent has high affinity to dopamine D2 receptor and serotonin 5-HT2A receptor. Blonanserin was as effective as risperidone in the treatment of schizophrenia, and showed greater efficacy in negative symptoms than haloperidol. Blonanserin was well tolerated in both the short- and long-term studies, and the frequency and intensity of EPS is generally similar with risperidone. For other side effects, blonanserine seems to have better safety profiles compared with other atypicals, and showed less prolactin elevation than risperidone. These findings suggest that blonanserin is useful in the treatment of schizophrenia.
Haloperidol ; Japan ; Korea ; Piperazines ; Piperidines ; Prolactin ; Receptor, Serotonin, 5-HT2A ; Receptors, Dopamine D2 ; Risperidone ; Schizophrenia ; Serotonin

OBJECTIVE: There are several lines of evidence suggested that a serotonergic dysfunction is involved in the susceptibility to suicide. Recently, the T102C polymorphism of the serotonin 2A receptor gene has been suggested to be associated with suicide, but the results of genetic study are still controversial. The purpose of this study was to test whether the T102C polymorphism of the serotonin 2A receptor gene indicates susceptibility to suicidal behavior. METHODS: The genotype and allele frequencies in the T102C polymorphism of the serotonin 2A receptor gene were studied by using TaqMan(R) assay to compare 80 Korean suicidal attempters with 125 Korean healthy controls. RESULTS: The genotype and allele frequencies did not differ between suicidal attempters and control subjects. And, there were no significant associations between the genotypes and violence or non-violence. We also did not find the significant association between the allelic frequencies and violence or non-violence. CONCLUSION: These findings suggest that the T102C polymorphism in serotonin 2A receptor gene is unlikely to play a role in the genetic susceptibility to suicidal behavior, violence or non-violence in Korean suicidal patients.
Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Receptor, Serotonin, 5-HT2A* ; Serotonin* ; Suicide ; Violence

OBJECTIVE: The aim of this study was to investigate the relationship between the -1438A/G polymorphism of serotonin receptor 2A (5HTR2A) and anxiety-related traits in Korean adolescent females. METHODS: A total of 174 Korean adolescent females were tested for the -1438A/G polymorphism of 5HTR2A using polymerase chain reaction (PCR)-based methods. Anxiety-related traits were evaluated using the Anxiety Sensitivity Index (ASI) and the trait form of the Spielberg State-Trait Anxiety Inventory (T-STAI). RESULTS: There was no difference between the genotypes with respect to scores pertaining to anxiety-related traits. Although the G allele carriers (GG or AG genotype) scored lower on the psychological subscale of the ASI (4.76+/-3.00 vs 5.98+/-4.00, p=0.038), this difference was not significant after Bonferroni correction. CONCLUSION: These findings suggest that the -1438A/G polymorphism of 5HTR2A might not be associated with anxiety sensitivity or trait anxiety.
Adolescent ; Alleles ; Anxiety ; Female ; Genotype ; Humans ; Polymerase Chain Reaction ; Receptor, Serotonin, 5-HT2A ; Serotonin*

OBJECTIVE: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. METHODS: One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). RESULTS: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. CONCLUSION: Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.
Antidepressive Agents ; Counseling ; Depression ; Depressive Disorder, Major ; Genotype ; Humans ; Psychotherapy ; Receptor, Serotonin, 5-HT1A ; Receptor, Serotonin, 5-HT2A ; Serotonin ; Serotonin Plasma Membrane Transport Proteins

OBJECTIVES: This study was designed to investigate the association between the silent mutation, 102T/C and the substitution of histidine by tyrosine at position 452, 452His/Tyr polymorphism of the 5HT2A receptor gene and schizophrenia in korean population. METHOD: 102T/C and 452His/Tyr polymorphism of the 5-HT2A receptor gene was typed with PCR in 93 patients with schizophrenia and 93 healthy controls. RESULTS: 1) Genotype of 102T/T, 102T/C, 102C/C were 37(40%), 34(36%), and 22(24%), res-pectively in the patients with schizophrenia. Genotype of 102T/T, 102T/C, 102C/C were 31(33%), 41(44%), and 21(23%), respectively in the controls, Allele frequencies of 102T in the patients with schizophrena was 0.58 and that in the controls was 0.55. Allele frequencies of 102C in the patients with schizophrena was 0.42 and that in controls was 0.45. There were no differencies in genotype and allele frequency of 102T/C between the patients with schizophrenia and the controls. 2) 452His/Tyr polymorphism of the 5-HT2A receptor gene was not founeded in the patients with schizophrenia and in the controls. CONCLUSION: These results suggest 102T/C and 452His/Tyr polymorphisms of the 5-HT2A receptor gene are not causally related to the development of schizophrenia in Korean population.
Gene Frequency ; Genotype ; Histidine ; Humans ; Polymerase Chain Reaction ; Receptor, Serotonin, 5-HT2A* ; Schizophrenia* ; Tyrosine

OBJECTIVE: The purpose of this study was to investigate the association between the T102C polymorphism in the serotonin 2A receptor gene and attention-deficit/hyperactivity disorder (ADHD) in Korean patients. METHODS: A total of 189 Korean children with ADHD as well as both parents of the ADHD children and 150 normal children participated in this study. DNA was extracted from blood samples from all of the subjects, and genotyping was conducted. Based on the allele and genotype information obtained, case-control analyses were performed to compare the ADHD and normal children, and Transmission disequilibrium tests (TDTs) were used for family-based association testing (number of trios=113). Finally, according to the significant finding which was showed in the case-control analyses, the results of behavioral characterastics and neuropsychological test were compared between ADHD children with and without the C allele. RESULTS: In the case-control analyses, statistically significant differences were detected in the frequencies of genotypes containing the C allele (chi2=4.73, p=0.030). In the family-based association study, TDTs failed to detect linkage disequilibrium of the T102C polymorphism associated with ADHD children. In the ADHD children, both the mean reaction time and the standard deviation of the reaction time in the auditory continuous performance test were longer in the group with the C allele compared to the group without the C allele. CONCLUSION: The results of this study suggest that there is a significant genetic association between the T102C polymorphism in the serotonin 2A receptor gene and ADHD in Korean children.
Alleles ; Case-Control Studies ; Child ; DNA ; Genotype ; Humans ; Linkage Disequilibrium ; Neuropsychological Tests ; Parents ; Reaction Time ; Receptor, Serotonin, 5-HT2A ; Serotonin