G861C Polymorphism Research Articles

Association between 5-HT1A receptor C-1019G, 5-HTTLPR polymorphisms and panic disorder: a meta-analysis.

HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging. A meta-analysis was conducted to test whether C-1019G polymorphism and 5-HTTLPR were involved in the etiology of PD. Articles researching the link between C-1019G, 5-HTTLPR polymorphisms, and PD were retrieved by database searching and systematically selected on the basis of selected inclusion parameters. 21 studies were included that examined the relationship of rs6295,5-HTTLPR polymorphisms with PD risk susceptibility (rs62957 polymorphism - 7 articles, and 5-HTTLPR polymorphism - 14 articles). A significant association was seen between the rs6295 polymorphism and PD pathogenesis, especially in Caucasian PD patients. No significant genetic linkage was found between the 5-HTTLPR polymorphism and PD. C-1019G polymorphism was involved in the etiology of PD in Caucasian patients. The 5-HTTLPR polymorphism was not a susceptibility factor of PD.

Association of HTR1A gene polymorphisms with obsessive–compulsive disorder and its treatment response: the influence of sex and clinical characteristics

Objective: There have been controversial results in the literature on the association between HTR1A polymorphisms (rs10042486, C-1019G, and Gly272Asp) and obsessive–compulsive disorder (OCD). Here, the plausibility for such genetic and pharmacogenetic association was investigated by assessing a sample of Iranian OCD patients.Method: OCD patients had fulfilled the criteria for DSM-IV-TR with Y-BOCS scores higher than 9. A total of 207 controls and 205 patients’ blood samples were genotyped by means of PCR-RFLP.Results: The results showed that there was no association between these three SNPs and the treatment response. The distribution of rs10042486 genotypes was significantly different in the patients compared to the controls. The association analyses of the C-1019G showed significant differences in the genotypic frequency of the patients with or without a positive family history of psychiatric disorders. Similar differences in female patients were also observed. We found that the age of onset also associates with the C-1019G polymorphism but only in the female patients. No association of Gly272Asp polymorphism and OCD was observed in this study.Conclusion: We concluded that among the HTR1A polymorphisms, only the association of rs10042486 CT genotype and OCD was statistically significant. The association of C-1019G with OCD by considering the age of onset and family history was just significant in the female patients. No significant association between the studied HTR1A SNPs with treatment response was observed. Acquiring both positive and negative pharmacogenetic outcomes in each population helps to select the appropriate medication for a particular patient with fewer side effects.

Escitalopram Response in Panic Disorder is Not Associated with Three 5-HT1A Receptor Gene Polymorphisms (Rs6295, Rs10042486, or Rs1364043) in Chinese-Han Patients

Background: Prior studies have implicated 5-HT1A receptor gene (HTR1A) polymorphisms in the etiology of panic disorder (PD) as well as in the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). A functional HTR1A C-1019G polymorphism (rs6295) in the promoter region and two non-synonymous polymorphisms (rs10042486 and rs1364043) were previously found to be associated with SSRI pharmacogenetics. However, no studies have examined this relationship in Chinese-Han PD patients. Methods: Seventy-seven patients with PD according to DSM-IV criteria were recruited. All of them with a minimum score of 8 on the seven item Panic Disorder Severity Scale, Chinese version (PDSS-CV). In this study, we evaluated the association between three single nucleotide polymorphisms (SNPs) of HTR1A (rs6295, rs10042486, and rs1364043) and the clinical effects of escitalopram in Chinese-Han PD patients. Results: The C/C genotype of C-1019G carriers showed better responses to escitalopram compared to the C/G or G/G genotypes. However, after Bonferroni correction, the effect was not statistically significant. Similarly, no significant associations were noted between rs10042486 or rs1364043 and the escitalopram clinical response. Conclusion: Our results suggest that these three single nucleotide polymorphisms (SNPs) in 5-HT1A genes examined here may not influence the escitalopram response in Chinese-Han PD patients.

A family-based association study of the HTR1B gene in eating disorders.

Objective:To explore the association of three polymorphisms of the serotonin receptor 1Dβ gene (HTR1B) in the etiology of eating disorders and their relationship with clinical characteristics.Methods:We analyzed the G861C, A-161T, and A1180G polymorphisms of the HTR1B gene through a family-based association test (FBAT) in 245 nuclear families. The sample was stratified into anorexia nervosa (AN) spectrum and bulimia nervosa (BN) spectrum. In addition, we performed a quantitative FBAT analysis of anxiety severity, depression severity, and Yale-Brown-Cornell Eating Disorders Scale (YBC-EDS) in the AN and BN-spectrum groups.Results:FBAT analysis of the A-161T polymorphism found preferential transmission of allele A-161 in the overall sample. This association was stronger when the sample was stratified by spectrums, showing transmission disequilibrium between the A-161 allele and BN spectrum (z = 2.871, p = 0.004). Quantitative trait analysis showed an association between severity of anxiety symptoms and the C861 allele in AN-spectrum participants (z = 2.871, p = 0.004). We found no associations on analysis of depression severity or preoccupation and ritual scores in AN or BN-spectrum participants.Conclusions:Our preliminary findings suggest a role of the HTR1B gene in susceptibility to development of BN subtypes. Furthermore, this gene might have an impact on the severity of anxiety in AN-spectrum patients.

Serotonin gene polymorphisms and lifetime mood disorders in predicting interferon-induced depression in chronic hepatitis C

BackgroundIFN-induced depression is a suitable model for investigating vulnerability to depression. We aimed at investigating the role of two vulnerability factors, lifetime mood disorder (LMD) and 5-HT-related gene polymorphisms in treated patients with infection by Hepatitis C Virus (HCV). MethodsDepressive symptoms of 130 consecutive HCV patients with no current psychopathology were measured during treatment with interferon and ribavirin. At baseline, LMD and 3 genotypes (5-HTTLPR, HTR1A, and TPH2) were also assessed. ResultsSubgroups of 43 patients with LMD, 96 with HTR1A-G allele, and 12 with both LMD and HTR1A-G homozigosity scored significantly higher to depression compared to the remaining patients during antiviral therapy. At the multiple regression analysis, LMD and HTR1A-G, whether separately or combined together, explained a similar amount of 10–22% of depression score variance, after controlling for the associated variables (age and gender). LimitationsHCV patients referred to a tertiary care center are not representative of all patients with chronic hepatitis C. Mediating factors, including proinflammatory cytokines and other potentially relevant gene polymorphisms, could not be evaluated. Patients were not stratified by degree of liver inflammation. LMD diagnoses were not cross-checked with medical records and IFN-induced depression was measured with a self-report scale only. ConclusionsHistory of mood disorders and HTR1A G allele variation, the C-1019G polymorphism of the transcriptional control region of the 5-HT1A receptor, independently predicted the incidence of IFN-induced depression in HCV patients, whether separately or jointly considered and although not reciprocally associated.

The association between romantic relationship status and 5-HT1A gene in young adults.

What factors determine whether or not a young adult will fall in love? Sociological surveys and psychological studies have shown that non-genetic factors, such as socioeconomic status, external appearance, and personality attributes, are crucial components in romantic relationship formation. Here we demonstrate that genetic variants also contribute to romantic relationship formation. As love-related behaviors are associated with serotonin levels in the brain, this study investigated to what extent a polymorphism (C-1019G, rs6295) of 5-HT1A gene is related to relationship status in 579 Chinese Han people. We found that 50.4% of individuals with the CC genotype and 39.0% with CG/GG genotype were in romantic relationship. Logistic regression analysis indicated that the C-1019G polymorphism was significantly associated with the odds of being single both before and after controlling for socioeconomic status, external appearance, religious beliefs, parenting style, and depressive symptoms. These findings provide, for the first time, direct evidence for the genetic contribution to romantic relationship formation.

Nonresponders to daily paroxetine and another SSRI in men with lifelong premature ejaculation: a pharmacokinetic dose-escalation study for a rare phenomenon.

PurposeNonresponse to any selective serotonin reuptake inhibitor (SSRI) treatment is rare. In this study, we aimed to investigate ejaculation delay nonresponse to paroxetine treatment in men with lifelong premature ejaculation (PE) who were also known to be nonresponders to other SSRIs.Materials and MethodsFive males with lifelong PE who were known nonresponders to paroxetine and other serotonergic antidepressants and eight males with lifelong PE who were specifically recruited were included. Blood sampling occurred 1 month and 1 day before the start of treatment and at the end of three consecutive series of 4 weeks of daily treatment with 10-, 20-, and 30-mg paroxetine, respectively. Blood samples for measurement of leptin and paroxetine were taken at 8:30 AM, 9:30 AM, 10:30 AM, and 11:30 AM, respectively. At 9:00 AM, one tablet of 10-, 20-, or 30-mg paroxetine was taken during the first, second, and third month, respectively. Intravaginal ejaculatory latency time (IELT) was measured with a stopwatch. The main outcome measures were the fold increase in the geometric mean IELT, serum leptin and paroxetine concentrations, body mass index (BMI), 5-HT1A receptor C-1019G polymorphism, and CYP2D6 mutations.ResultsBetween the 7 paroxetine responders and 6 nonresponders, the fold increase in the geometric mean IELT was significantly different after daily 10-mg (p=0.003), 20-mg (p=0.002), and 30-mg paroxetine (p=0.026) and ranged from 2.0 to 8.8 and from 1.1 to 1.7, respectively. BMI at baseline and at the end of the study was not significantly different between responders and nonresponders. Serum leptin levels at baseline were similar in responders and nonresponders and did not change during treatment. The serum paroxetine concentration increased with increasing dosage and was not significantly different between responders and nonresponders. There was no association between the fold increase in the geometric mean IELT and serum paroxetine levels during the three treatment periods nor between leptin levels during the treatment periods and serum paroxetine levels. For the 5-HT1A receptor C-1019G variation, all responders had the CC genotype and all nonresponders had the GC genotype, respectively.ConclusionsComplete absence of paroxetine-induced ejaculation delay is presumably related to pharmacodynamic factors and perhaps to 5-HT1A receptor gene polymorphism.

Genetic association of 5-HT1A and 5-HT1B gene polymorphisms with migraine in a Turkish population

Migraine, a very common headache disorder, is regarded as a polygenic disease and serotonergic pathways appear to play a major role in its pathogenesis. The present study was designed to explore the associations of polymorphisms of 5-hydroxytryptamine (serotonin) receptor 1A (5-HT1A) and 5-hydroxytryptamine receptor 1B (5-HT1B) genes in Turkish migraine patients. 5-HT1A C-1019G (rs6295) promoter and 5-HT1B G861C (rs6296) exon polymorphisms in 203 migraine patients and 202 healthy subjects were analyzed by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Allele and genotype frequencies were not significantly different between migraine patients and healthy subjects for both the 5-HT1A C-1019G promoter and 5-HT1B G861C exon polymorphisms. Our data do not support the hypothesis that 5-HT1A C-1019G and 5-HT1B G861C polymorphisms have effects on migraine.

Sertraline (Zoloft) response in major depressive disorder is not associated with three 5-HT1A receptor gene polymorphisms (rs6295, rs10042486, or rs1364043) in Chinese-Han patients

The 5-HT1A receptor gene (HTR1A) polymorphisms have been implicated in the etiology of major depressive disorder and in the therapeutic response to selective serotonin reuptake inhibitors (SSRIs). Previous studies have investigated the potential association of a functional HTR1A C-1019G polymorphism (rs6295C/G) in the promoter region with SSRIs pharmacogenetics in Caucasian (Serretti et al., 2004; Parsey et al., 2006; Levin et al., 2007), Japanese (Kato et al., 2009), and Chinese (Hong et al., 2006); however, the results have been inconsistent. In addition, Kato et al. (2009) found that two nonsynonymous polymorphisms (rs10042486C/T and rs1364043G/ T) were associated with greater response to antidepressants in Japanese. In this study, we investigated whether these three HTR1A polymorphisms are related to the antidepressant effects of sertraline (Zoloft) in ChineseHan patients.

Association between the 5-HT1A receptor gene polymorphism (rs6295) and antidepressants

Previous studies have implicated 5-HT1A receptor gene (HTR1A) polymorphisms in the therapeutic response to antidepressants, especially selective serotonin reuptake inhibitors. A functional HTR1A C-1019G polymorphism (rs6295) in the promoter region was found to be associated with antidepressant pharmacogenetics in different populations. However, inconsistent and inconclusive results have been obtained. In this study, we tested whether rs6295 genetic variants are related to antidepressant effects using a meta-analysis method. The relevant literature was acquired through deliberate searching and selection based on the established inclusion criteria for publications. A total of 10 articles were identified, all of which evaluated the HTR1A C-1019G polymorphism and antidepressant response. Dominant and recessive models were tested in the analyses, and the results revealed no association between the HTR1A C-1019G polymorphism and antidepressant response.

Interaction between Serotonin Transporter and Serotonin Receptor 1 B genes polymorphisms may be associated with antisocial alcoholism

BackgroundSeveral studies have hypothesized that genes regulating the components of the serotonin system, including serotonin transporter (5-HTTLPR) and serotonin 1 B receptor (5-HT1B), may be associated with alcoholism, but their results are contradictory because of alcoholism’s heterogeneity. Therefore, we examined whether the 5-HTTLPR gene and 5-HT1B gene G861C polymorphism are susceptibility factors for a specific subtype of alcoholism, antisocial alcoholism in Han Chinese in Taiwan.MethodsWe recruited 273 Han Chinese male inmates with antisocial personality disorder (ASPD) [antisocial alcoholism (AS-ALC) group (n = 120) and antisocial non-alcoholism (AS-N-ALC) group (n = 153)] and 191 healthy male controls from the community. Genotyping was done using PCR-RFLP.ResultsThere were no significant differences in the genotypic frequency of the 5-HT1B G861C polymorphism between the 3 groups. Although AS-ALC group members more frequently carried the 5-HTTLPR S/S, S/LG, and LG/LG genotypes than controls, the difference became non-significant after controlling for the covarying effects of age. However, the 5-HTTLPR S/S, S/LG, and LG/LG genotypes may have interacted with the 5-HT1B G861C C/C polymorphism and increased the risk of becoming antisocial alcoholism.ConclusionOur study suggests that neither the 5-HTTLPR gene nor the 5-HT1B G861C polymorphism alone is a risk factor for antisocial alcoholism in Taiwan’s Han Chinese population, but that the interaction between both genes may increase susceptibility to antisocial alcoholism.

Endophenotypes and serotonergic polymorphisms associated with treatment response in obsessive-compulsive disorder

OBJECTIVES:Approximately 40-60% of obsessive-compulsive disorder patients are nonresponsive to serotonin reuptake inhibitors. Genetic markers associated with treatment response remain largely unknown. We aimed (1) to investigate a possible association of serotonergic polymorphisms in obsessive-compulsive disorder patients and therapeutic response to selective serotonin reuptake inhibitors and (2) to examine the relationship between these polymorphisms and endocrine response to intravenous citalopram challenge in responders and non-responders to serotonin reuptake inhibitors and in healthy volunteers.METHODS:Patients with obsessive-compulsive disorder were classified as either responders or non-responders after long-term treatment with serotonin reuptake inhibitors, and both groups were compared with a control group of healthy volunteers. The investigated genetic markers were the G861C polymorphism of the serotonin receptor 1Dβ gene and the T102C and C516T polymorphisms of the serotonin receptor subtype 2A gene.RESULTS:The T allele of the serotonin receptor subtype 2A T102C polymorphism was more frequent among obsessive-compulsive disorder patients (responders and non-responders) than in the controls (p<0.01). The CC genotype of the serotonin receptor subtype 2A C516T polymorphism was more frequent among the non-responders than in the responders (p<0.01). The CC genotype of the serotonin receptor subtype 1Dβ G681C polymorphism was associated with higher cortisol and prolactin responses to citalopram (p<0.01 and p<0.001, respectively) and with a higher platelet-rich plasma serotonin concentration among the controls (p<0.05). However, this pattern was not observed in the non-responders with the same CC genotype after chronic treatment with serotonin reuptake inhibitors. This CC homozygosity was not observed in the responders.

Serotonin gene polymorphisms and psychiatry comorbidities in temporal lobe epilepsy

Neuropsychiatric comorbidities are frequent in temporal lobe epilepsy (TLE). It is biologically plausible that alterations in serotonin-related genes may be involved in higher susceptibility to psychiatric disease in these individuals. Here we report results of an association study of serotonin gene polymorphisms and psychiatry comorbidities in TLE. Case-control study of 155 patients with temporal lobe epilepsy. We evaluate the influence of 5-HTTLPR and 5-HTTVNTR polymorphisms in the 5-HTT gene and the C-1019G polymorphism in the 5-HT1A gene in psychiatric comorbidities of TLE. After logistic regression, female sex (OR=2.34; 95% CI 1.06-5.17; p=0.035) and the presence of C allele of 5-HT1A C-1019G polymorphism (OR=2.77; 95% CI 1.01-7.63; p=0.048) remained independent risk factors for anxiety disorders in temporal lobe epilepsy. C allele of 5-HT1A C-1019G polymorphism might be an independent risk factor for anxiety disorders in temporal lobe epilepsy. We believe that other studies in this venue will shade some light on molecular mechanisms involved in psychiatric comorbidities in epilepsy.

Effect of Serotonin-Related Gene Polymorphisms on Pathogenesis and Treatment Response in Korean Schizophrenic Patients

Serotonin has been implicated in the pathophysiology of several psychiatric disorders including schizophrenia. Serotonergic system-related genes may be good candidates in investigating the genetic basis of schizophrenia. We aimed to investigate the associations of HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T variants with schizophrenia. A total of 202 patients with schizophrenia and 165 normal controls were genotyped for HTR1A C-1019G, HTR2A-1438A/G, TPH1 218A/C, and TPH2-703G/T single nucleotide polymorphisms (SNPs). In order to assess the severity of a patient's psychiatric symptoms, the brief psychiatric rating scale (BPRS), the positive and negative symptom scale (PANSS), and the Calgary depression scale for Schizophrenia (CDSS) were administered. Genotype and allele frequencies were compared between groups via χ(2) statistics. Associations between the genotypes of candidate SNPs with the severity of symptoms were examined with ANOVA by comparing the mean scores of BPRS, PANSS, and CDSS according to genotype. No significant differences in the genotype distributions and allele frequencies of four SNPs were found between patients with schizophrenia and normal controls. There was a trend towards association of HTR1A C-1019G polymorphism with negative symptom. Negative symptom score of PANSS was lower in the patients with CC genotype than in the G allele carriers. These results suggested that C allele might be associated with lesser negative symptom. More studies are needed to confirm these findings. In the future, we plan to study the associations between schizophrenia and other genetic polymorphisms.

Association study between genetic monoaminergic polymorphisms and OCD response to clomipramine treatment

In the present paper, we investigated the 5HTTLPR and STin2 polymorphisms in the promoter region of the serotonin transporter gene (SLC6A4), the G861C polymorphism (rs6296) of the serotonin receptor 1D beta (HTR1B), the T102C (rs6113) and C516T (rs6305) polymorphisms of the serotonin receptor gene subtype 2A (HTR2A), the DAT UTR, DAT intron 8 and DAT intron 14 of the dopamine transporter gene (SLC6A3), the Val-158-Met (rs4680) polymorphism of the COMT and the silent mutation G1287A (rs5569) in the norepinephrine transporter gene (SLC6A2). We genotyped 41 obsessive-compulsive disorder (OCD) outpatients, classified as good-responders (n=27) and poor-responders (n=14) to treatment with clomipramine according to the Yale Brown Obsessive-Compulsive Scale (YBOCS). Patients who achieved a reduction in symptoms of 40% or more in YBOCS after 14 weeks of treatment were considered good-responders. Genotypes and alleles distribution of the investigated polymorphisms were compared between both groups. We did not find association between the studied polymorphisms and clomipramine response in our sample.

Meta‐analyses suggest association between COMT, but not HTR1B, alleles, and suicidal behavior

Several studies have suggested that suicidal behavior is at least partially determined by genetic factors, supporting a search for related genes. Two genes that have been highlighted in the literature as being involved are HTR1B, which codes for the serotonin 1B receptor, and COMT, which is related to the inactivation of catecholamines. In order to assess the combined evidence for the numerous studies that have been published relating suicidal behavior to these two genes, two different random effects meta-analyses were conducted utilizing seven studies related to HTR1B and six studies related to COMT. For HTR1B, the combined evidence from 789 case and 1,247 control subjects/participants, suggested that there was no significant association between the HTR1B G861C polymorphism and suicidal behavior. For COMT, based on the combined data from 519 cases and 933 control subjects, there was evidence of a significant association between the COMT 158Met polymorphism and suicidal behavior. Although the results for COMT were not influenced by publication bias, the significance of the combined results was not robust and was related to the gender of the case and control subjects. The results for COMT support past literature that has found a relationship between suicidal behavior and COMT, and has also found that the relationship differs for males and females. Given that in the United States a higher proportion of females attempt suicide, and the higher proportion of males successfully commit suicide, it is possible that COMT is related to the lethality of suicide attempts.

Functional polymorphisms of the 5-HT1A and 5-HT1B receptor are associated with clinical symptoms in migraineurs

Migraine is regarded as a polygenic disease and serotonergic pathways appear to play a major role in its pathogenesis. In the present study, the role of the 5-HT1A and 5-HT1B receptors in migraine was evaluated. The human 5-HT1A receptor gene transcription is modulated by a functional C-1019G promoter polymorphism. The 5-HT1B receptor is the main effector of vasoconstriction in meningeal and cerebral arteries and its functional G861C promoter polymorphism was investigated. We report a positive association of the GG genotype of the 5-HT1A promoter polymorphism with avoidance of physical activity during a migraine attack in comparison to the CC genotype (p = 0.008). Moreover, a positive association of the CC genotype of the G861C polymorphism of the 5-HT1B receptor with the reported intensity of the headache attack on the visual analogue scale was observed (CC 8.3 +/- 1.5 vs. GG 6.9 +/- 1.8; p < 0.05). An association of either polymorphism with migraine with or without aura could not be found. For the first time, our results indicate a role of allelic variation of the 5-HT1A receptor in motion related discomfort in migraineurs and a role of the 5-HT1B receptor polymorphism in headache intensity.

Association study of two serotonin 1A receptor gene polymorphisms and fluoxetine treatment response in Chinese major depressive disorders

The firing rate of dorsal raphe serotonergic neurons is modulated by somatodendritic 5-hydroxytryptamine 1A (HTR1A) autoreceptors. Evidence from animal and clinical studies has suggested that desensitization of HTR1A is implicated in the antidepressant therapeutic mechanism of selective serotonin reuptake inhibitors (SSRIs). Recent studies, including our recent findings, have reported that a functional HTR1A C-1019G polymorphism in the promoter region, as well as a nonsynonymous polymorphism, Gly272Asp, may be associated with SSRI pharmacogenetics. In this study, we tested whether Gly272Asp genetic variants are related to a 4-week fluoxetine antidepressant effect in 222 Chinese major depressive patients. We also tested the linkage disequilibrium (LD) measurement between HTR1A Gly272Asp and C-1019G polymorphisms, and haplotype analysis was conducted to assess the association between the two markers within the HTR1A gene and fluoxetine antidepressant response. The results show that the HTR1A Gly272Asp polymorphism was not associated with fluoxetine therapeutic response. The two markers are in strong LD and the HTR1A haplotype of the two polymorphisms is associated with fluoxetine therapeutic response. This association is gender-specific and mostly arises from the effect of HTR1A C-1019G polymorphism: female patients with -1019C/C genotype showed a better response than -1019G carriers. These findings need to be confirmed in other ethnic populations.

Higher 5-HT1A Receptor Binding Potential During a Major Depressive Episode Predicts Poor Treatment Response: Preliminary Data from a Naturalistic Study

Serotonin 1A (5-HT1A) binding potential (BP) as assessed by positron emission tomography (PET) is higher in major depressive disorder (MDD) in association with the higher expressing GG genotype of the 5-HT1A C-1019G polymorphism. We hypothesize that higher 5-HT1A BP and the GG genotype predict remission failure on antidepressant treatment. We determined 5-HT1A BP by PET and 5-HT1A C-1019G genotype in 43 controls and 22 medication-free MDD subjects. MDD was treated naturalistically and remission was defined as >50% reduction and a score of <or=10 on the 24 item Hamilton Scale 1 year after initiation of treatment after scanning. Despite equivalent treatment, nonremitters have higher pretreatment cortical BP and the GG genotype is over-represented compared with remitters. Higher 5-HT1A BP, perhaps due to greater gene expression, may predict antidepressant medication nonremission. The findings should be tested in a controlled prospective treatment study.

Response to fluoxetine and serotonin 1A receptor (C-1019G) polymorphism in Taiwan Chinese major depressive disorder

Serotonin systems appear to play a key role in the pathogenesis of major depression and the therapeutic mechanisms of antidepressants. The firing rate of dorsal raphe serotonergic neurons is controlled by somatodendritic 5-hydroxytryptamine 1A (HTR1A) autoreceptors, and desensitization of these receptors is implicated in the antidepressant mechanism of selective serotonin reuptake inhibitors. We tested whether a functional polymorphism (C-1019G) in the promoter region of the HTR1A gene and serotonin-related genetic variants are related to fluoxetine antidepressant effect. We genotyped the HTR1A C-1019G polymorphism as well as polymorphisms in the serotonin transporter gene-linked polymorphic region (SERTPR), variable-number tandem-repeat polymorphisms in intron 2 (STin2) of the serotonin transporter gene, serotonin 2A receptor (T102C), tryptophan hydroxylase (A218C), and G-protein beta3 subunit (C825T) in 224 Chinese patients from southern Taiwan with major depression, who accepted 4-week fluoxetine treatment and therapeutic evaluation. Our results demonstrated that the HTR1A -1019C/C carriers (P=0.009) and SERTPR l/l carriers (P<0.001) showed a better response to fluoxetine, while other polymorphisms were not associated with fluoxetine therapeutic response. The major limitation of this study is the lack of a placebo control. Future prospective study with placebo control may help to predict and individualize antidepressant treatment.