HTR2A Polymorphisms Research Articles

Impact of Pharmacogenetic Testing on Clozapine Treatment Efficacy in Patients with Treatment-Resistant Schizophrenia.

Managing schizophrenia with clozapine poses a significant challenge due to prevalent therapeutic failures. The increasing interest in personalized medicine underscores the importance of integrating pharmacogenetic information for effective pharmacotherapeutic monitoring in patients. The objective of this study was to explore the correlation between DRD2, HTR2A, SLC6A4, CYP1A2, and ABCB1 polymorphisms and clozapine response in 100 patients with Treatment-Resistant Schizophrenia. Different scales such as the Positive and Negative Syndrome Scale (PANSS), the Warwick-Edinburgh Mental Wellbeing Scale (SWEMWBS), the Global Assessment of Functioning Scale (GAF), the Brief Negative Symptom Scale (BNSS), and pharmacokinetic parameters were used to analyse the efficacy of the treatment. Patients who exclusively responded to clozapine compared to the patients with augmentation strategies exhibited distinctive features, such as lower doses, plasma levels, and presented less-pronounced symptomatology. Genetic associations were explored, highlighting SLC6A4, HTR2A, and the *1F/*1F polymorphism for the CYP1A2 gene.

ЗВ'ЯЗОК ПОЛІМОРФІЗМУ Т102C (rs6313) ГЕНУ РЕЦЕПТОРУ СЕРОТОНІНУ HTR2A З РОЗВИТКОМ ДЕПРЕСИВНИХ РОЗЛАДІВ У ДІТЕЙ З СОМАТОФОРМНОЮ ВЕГЕТАТИВНОЮ ДИСФУНКЦІЄЮ ДИХАЛЬНОЇ СИСТЕМИ

This text is the thesis of the VI scientific and practical conference with international participation "PSYCHOSOMATIC MEDICINE: SCIENCE AND PRACTICE", which will be held on November 2-3, 2023 in the format of online broadcasting. The following is devoted to the study of the relationship between the T102C (rs6313) serotonin receptor gene HTR2A polymorphism and the risk of developing somatoform vegetative dysfunctions of the respiratory system.

Association of HTR2A and HTR2C gene polymorphisms and the efficacy of rehabilitation measures in narcology patients

In recent years, there has been an increase in the number of patients with combined addiction to several psychoactive substances, as well as with addiction to psychostimulants. Meanwhile, there are no methods of rehabilitation of these patients based on clinical characteristics and the state of patients’ genetic biomarkers within the personalized approach. It seems relevant to study the influence of some pathogenetic biomarkers on the efficacy of rehabilitation measures in patients with combined addiction to several psychoactive substances and psychostimulant addiction in order to improve the quality of medical care for these patients. The aim of the study was to determine the association of HTR2A and HTR2C gene polymorphisms and the effectiveness of rehabilitation measures in patients with combined addiction to several psychoactive substances and psychostimulant addiction. Materials and methods. The study included 325 patients with combined addiction to several psychoactive substances and psychostimulant addiction. Methods: clinical and psychopathological, anamnestic, catamnestic, molecular genetics, and statistical methods. The effectiveness of rehabilitation work was assessed by the number of patients who chose treatment in the conditions of inpatient or outpatient rehabilitation due to primary motivational work with them and by the duration of remission as a result of the program. The results of the study. The patients were divided into 3 groups: patients with only psychostimulant addiction, patients with combined addiction to several psychoactive substances, and those with psychostimulant addiction and comorbid psychiatric pathology. The association of polymorphism of genes controlling the work of the serotonin system of the brain (HTR2A and HTR2C) and the efficacy of motivational work aimed at undergoing a rehabilitation program and the duration of remissions was revealed. Conclusion. Based on the analysis of the obtained results, the association of some clinical characteristics and HTR2A and HTR2C gene polymorphisms with the effectiveness of rehabilitation measures in patients with combined addiction to several psychoactive substances, psychostimulant addiction, and with comorbid psychiatric pathology was established.

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the chinese Han population

BackgroundLifelong premature ejaculation (LPE) is one of the most common ejaculatory dysfunctions in men. The serotonin (5-HT) synthesis rate-limiting enzyme (TPH2) and receptor (HTR1A) in the 5-HT regulatory system may play a key role in the pathogenesis of LPE. However, there are few studies on the effects of TPH2 and HTR1A polymorphisms on LPE risk. We speculated that TPH2 and HTR1A polymorphisms may affect the occurrence and development of LPE in the Chinese Han population.MethodsIn this study, 91 patients with LPE and 362 normal controls aged 18 to 64 years were enrolled in the male urology department of Hainan General Hospital in China from January 2016 to December 2018. The SNPs in HTR1A and TPH2, which are related to 5-HT regulation, were selected as indexes to genotype the collected blood samples of participants. Logistic regression was used to analyze the correlation between SNPs of HTR1A and TPH2 with LPE susceptibility, as well as the relationship with leptin, 5-HT and folic acid levels.ResultsThe results revealed that HTR1A-rs6295 increased LPE risk in recessive model. Rs11178996 in TPH2 significantly reduced susceptibility to LPE in allelic (odds ratio (OR) = 0.68, 95% confidence interval (95% CI) = 0.49–0.96, p = 0.027), codominant (OR = 0.58, 95% CI = 0.35–0.98, p = 0.040), dominant (OR = 0.58, 95% CI = 0.36–0.92, p = 0.020), and additive (OR = 0.71, 95% CI = 0.52–0.98, p = 0.039) models. Grs11179041Trs10879352 could reduce the risk of LPE (OR = 0.44, 95% CI = 0.22–0.90, p = 0.024) by haplotype analysis.ConclusionHTR1A-rs6295 and TPH2-rs11178996 are associated with LPE risk in the Chinese Han population based on the finding of this study.

Platelet Serotonin (5-HT) Concentration, Platelet Monoamine Oxidase B (MAO-B) Activity and HTR2A, HTR2C, and MAOB Gene Polymorphisms in Asthma.

The complex role of the serotonin system in respiratory function and inflammatory diseases such as asthma is unclear. Our study investigated platelet serotonin (5-HT) levels and platelet monoamine oxidase B (MAO-B) activity, as well as associations with HTR2A (rs6314; rs6313), HTR2C (rs3813929; rs518147), and MAOB (rs1799836; rs6651806) gene polymorphisms in 120 healthy individuals and 120 asthma patients of different severity and phenotypes. Platelet 5-HT concentration was significantly lower, while platelet MAO-B activity was considerably higher in asthma patients; however, they did not differ between patients with different asthma severity or phenotypes. Only the healthy subjects, but not the asthma patients, carrying the MAOB rs1799836 TT genotype had significantly lower platelet MAO-B activity than the C allele carriers. No significant differences in the frequency of the genotypes, alleles, or haplotypes for any of the investigated HTR2A, HTR2C and MAOB gene polymorphisms have been observed between asthma patients and healthy subjects or between patients with various asthma phenotypes. However, the carriers of the HTR2C rs518147 CC genotype or C allele were significantly less frequent in severe asthma patients than in the G allele carriers. Further studies are necessary to elucidate the involvement of the serotonergic system in asthma pathophysiology.

Association of GABRG3, GABRB3, HTR2A gene variants with autism spectrum disorder

Autism spectrum disorder (ASD) is a neurodevelopmental and neurobehavioral disorder characterized by impaired social communication, repetitive and restricted patterns of behavior, activity, or interest, and altered emotional processing. Reported prevalence is 4 times higher in men and it has increased in recent years. Immunological, environmental, epigenetic, and genetic factors play a role in the pathophysiology of autism. Many neurochemical pathways and neuroanatomical events are effective in determining the disease. It is still unclear how the main symptoms of autism occur because of this complex and heterogeneous situation. In this study, we focused on gamma amino butyric acid (GABA) and serotonin, which are thought to contribute to the etiology of autism; it is aimed to elucidate the mechanism of the disease by investigating variant changes in the GABA receptor subunit genes GABRB3, GABRG3 and the HTR2A gene, which encodes one of the serotonin receptors.200 patients with ASD between the ages of 3–9 and 100 healthy volunteers were included in the study. Genomic DNA isolation was performed from peripheral blood samples taken from volunteers. Genotyping was performed using the RFLP method with PCR specific for specific variants. Data were analyzed with SPSS v25.0 program.According to the data obtained in our study; In terms of HTR2A (rs6313 T102C) genotypes, the homozygous C genotype carrying frequency in the patient group and the homozygous T genotype carrying frequency in the GABRG3 (rs140679 C/T) genotypes were found to be significantly higher in the patient group compared to the control group (*p: 0.0001, p: 0.0001). It was determined that the frequency of individuals with homozygous genotype was significantly higher in the patient group compared to the control group and having homozygous genotypes increased the disease risk approximately 1.8 times. In terms of GABRB3 (rs2081648 T/C) genotypes, it was determined that there was no statistically significant difference in the frequency of carrying homozygous C genotype in the patient group compared to the control group (p: 0.36).According to the results of our study, we think that the HTR2A (rs6313 T102C) polymorphism is effective in modulating the empathic and autistic characteristics of individuals, and that the HTR2A (rs6313 T102C) polymorphism is more distributed in the post-synaptic membranes in individuals with a higher number of C alleles. We believe that this situation can be attributed to the spontaneous stimulatory distribution of the HTR2A gene in the postsynaptic membranes because of T102C transformation.In genetically based autism cases, carrying the point mutation in the rs6313 variant of the HTR2A gene and the C allele and the point mutation in the rs140679 variant of the GABRG3 gene and accordingly carrying the T allele provide a predisposition to the disease.

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the Chinese Han population

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the Chinese Han population

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the Chinese Han population

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the Chinese Han population

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the Chinese Han population

Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the Chinese Han population

Associations between Anxiety, Depression, Chronic Pain and Oral Health-Related Quality of Life, Happiness, and Polymorphisms in Adolescents’ Genes

Adolescence is marked by changes and vulnerability to the emergence of psychological problems. This study aimed to investigate associations between anxiety/depression/chronic pain and oral health-related quality of life (OHRQoL)/happiness/polymorphisms in the COMT, HTR2A and FKBP5 genes in Brazilian adolescents. A cross-sectional study was conducted with ninety adolescents 13 to 18 years. Anxiety, depression and chronic pain were evaluated using the RDC/TMD. The Oral Health Impact Profile was used to assess oral OHRQoL. The Subjective Happiness Scale was used to assess happiness. Single-nucleotide polymorphisms in COMT (rs165656, rs174675), HTR2A (rs6313, rs4941573) and FKBP5 (rs1360780, rs3800373) were genotyped using the Taqman® method. Bivariate and multivariate logistic regression analyses were performed (p < 0.05). Chronic pain and depression were associated with feelings of happiness (p < 0.05). A significant inverse association was found between anxiety and OHRQoL (p = 0.004). The presence of minor allele C of COMT rs174675 was significantly associated with depression (p = 0.040). Brazilian adolescents with depression and chronic pain considers themselves to be less happy than others and those with anxiety are more likely to have a negative impact on OHRQoL. Moreover, the rs174675 variant allele in the COMT gene was associated with depressive symptoms in Brazilian adolescents.

Pharmacogenomics of MDD as a Developing Field: Challenges and Opportunities

While first gene-drug pairs have emerged to be clinically actionable in the treatment of major depressive disorders (MDD) (e.g., CYP2D6 and TCAs/SSRIs), genomic studies have not yet been successful in identifying replicable and valid biomarkers of pharmacological treatment outcome. While some trials suggest that candidates such as CYP2D6, CYP2C19, CYP1A2, SLC6A4 and HTR2A polymorphisms may improve the prediction of response/remission, these results should be interpreted cautiously and required confirmation in larger samples. This presentation will cover state of the art of pharmacogenomics for MDD as well as the emerging field of pharmacotranscriptomics and functional genomics analyses in MDD. Specifically, pharmacotranscriptomics in combination with genomics may be a promising avenue in overcoming some of the current limitations in treatment response prediction research. More recently, the combined genetic effect of polygenic risk scores has shown promising results in predicting treatment response. Importantly, adequately large and well phenotyped clinical trials are required to be conducted with pharmacogenomics/-transcriptomics prospectively in mind.DisclosureNo significant relationships.

A Cross-Sectional Study on the Relationship Among Cytokines, 5-HT2A Receptor Polymorphisms, and Sleep Quality of Non-manual Workers in Xinjiang, China

BackgroundStudies have shown that cytokine activity changes during the sleep-wake process, suggesting that inflammatory factors may be involved in a mechanism affecting sleep quality. Furthermore, the serotonergic system is also one of the essential components of airway relaxation during sleep, especially the serotonin 2A receptor (5-HTR2A) type that plays an important role in the sleep-wake process. Therefore, this research aimed to investigate the effects of cytokines and 5-HTR2A polymorphisms on sleep quality in non-manual workers in Urumqi, Xinjiang in order to explore the relationship between the three.MethodsThis study used a cluster sampling method to randomly select non-manual workers who worked in Urumqi, Xinjiang for at least 1 year. From July 2016 and December 2017, this study recruited 1,500 non-manual workers for physical examination in the First Affiliated Hospital of Xinjiang Medical University. According to the inclusion and exclusion criteria, 1,329 non-manual workers were finally included in the questionnaire study. It used the Pittsburgh Sleep Quality Index questionnaire to assess sleep quality. Moreover, another 15% of respondents were randomly selected as the experimental study group. The polymerase chain reaction restriction fragment length polymorphism was used to detect 5-HTR2A gene genotypes. Simultaneously, the cytokine (IL-1β, IL-2, IL-6, and TNF-α) content was evaluated using an enzyme-linked immunoassay.ResultsThe results showed that among the 1,329 respondents, 870 had sleep quality problems, and the detection rate was 65.46%. The distribution of −1438G/A genotypes in the 5-HTR2A gene was significantly different among different sleep quality groups (p < 0.05), with no statistical significance present when comparing to T102C (p > 0.05). Logistic regression analysis showed that the AG [odds ratio (OR) = 2.771, 95% confidence interval (CI): 1.054–7.287] and GG (OR = 4.037, 95% CI: 1.244–13.105) genotypes at −1438G/A loci were both associated with poor sleep quality and were thus considered the susceptibility genotypes for sleep problems. Furthermore, IL-1β was shown to be a protective factor for sleep quality (OR = 0.949, 95% CI: 0.925–0.974). The interaction results showed that AG × IL-1β (OR = 0.952, 95% CI: 0.918–0.987) was associated with a lower risk of sleep problems than AA × IL-1β.ConclusionCytokines and 5-HTR2A polymorphisms not only have independent effects on sleep but also may have cumulative effects. Therefore, it is necessary to further explore the related mechanisms affecting sleep quality to improve the sleep quality of non-manual workers.

Serotonin 5-HT2A receptor polymorphisms are associated with irritability and aggression in conduct disorder

In childhood and adolescence, overt antisocial and aggressive manifestations are typically diagnosed as conduct disorder (CD). Given that the emerging research has pointed to the influence of 5-HT2A receptors in the ontogeny of aggression, we aimed to analyze the association of its genetic polymorphisms with CD. The study included 228 male adolescent subjects (120 with and 108 without CD). CD was diagnosed according to Structured Clinical Interview for DSM-IV criteria, while evaluations of aggressive/dissociative behaviors were performed using psychometric questionnaires including the PCL-YV, OAS-M, KADS, and CBCL. Platelet 5-HT concentration was determined by spectrophotofluorometry. Genotyping of 5-HT2A receptor polymorphisms rs2070040, rs9534511, rs4142900, rs9534512 was performed using TaqMan SNP Genotyping Assays. Subjective irritability, physical aggression toward others, and antisocial behavior were strongly associated with the G allele of rs2070040 and rs4142900, and the C allele of rs9534511 and rs9534512. A significantly increased platelet 5-HT concentration in CD subjects, compared to controls, was lost after the correction according to the smoking status. Our results indicate an association of the studied HTR2A polymorphisms and their haplotypes with irritability and impulsivity traits, which may contribute to the aggressive and antisocial behavior in male adolescents with CD.

Effects of Smoking on Aggression, Big Five Personality Factors, and Polymorphisms in HTR2A, DRD4, and MAOA among Egypt University Students.

Introduction To find genetic variants in the DRD4 and HTR2A genes' promoter regions and exons that are associated with tobacco smoking and nicotine addiction in Egyptian university students as well as to study the association between personality traits and smoking status. Methods A self-administered questionnaire about cigarette smoking and personality attributes (Big Five Inventory, ESPAD Questionnaire on Substance Abuse, and Buss-Perry Aggression Questionnaire). The participants in the study were 90 nonsmokers (NS) and 88 current smokers (CS), who were divided into two groups depending on their cigarette consumption per day (cpd): 55 heavy smokers (HS, >20 cpd) and 33 light smokers (LS, 1–10 cpd). Four and eight single nucleotide polymorphisms (SNPs) in the DRD4, HTR2A, and MOA genes, respectively, were genotyped. Results Smokers scored lower on neuroticism, agreeableness, conscientiousness, openness, and extraversion than nonsmokers, but higher on aggression. Furthermore, the C allele of rs1800955 in DRD4 was associated with cigarette smoking in the HS vs. NS and LS vs. NS studies. The T allele of the HTR2A rs6313 gene was discovered to be strongly associated with cigarette smoking. There was no link discovered between MOA rs1137070 and MOA rs1137070. Conclusions Using a comprehensive personality model (FFM), this study repeats and extends earlier research. Personality and genetic studies may aid in the development of a more complete and conclusive understanding of cigarette smoking, as well as more precise policies and guidelines for smoking cessation and quitting.

Association of polymorphisms of the genes HTR2A and 5-HTT with smoking in Yakuts

Association of polymorphisms of the genes HTR2A and 5-HTT with smoking in Yakuts

Relationship between Serotonin-2A Receptor Gene Polymorphism and Wound Healing in Brazilian Patients

HIGHLIGHTS The platelets serotonin stands out in obtaining wound healing closure. Serotonin receptor gene (5-HTR2A) polymorphisms can cause alterations in the tissue repair. 102T-C polymorphism in the 5-HTR2A gene is associated to alterations in wound healing process.

5-HTR2A Polymorphisms rs6311 and rs6313 and Major Depressive Disorder: A Meta-Analysis

rs6311 and rs6313 are two Single Nucleotide Polymorphisms (SNPs) on the Serotonin Receptor 2A gene (5-HTR2A) in complete linkage disequilibrium. Numerous gene association studies have examined the relationships between one or both of these two polymorphisms and Major Depressive Disorder (MDD), with conflicting results. The present meta-analysis examined 19 case-control gene association studies, 9 of which included rs6311 (n = 3382), and 15 of which included rs6313 (n = 5590). The strength of relationship with MDD was assessed by pooled odds ratios and 95% confidence intervals for both SNPs according to four genetic models. Heterogeneity was measured by Q and I2. Subgrouping was performed by minor allele and by ethnicity. Results were nonsignificant for all models and subgroups, suggesting that genotype alone does not play a major role in genetic susceptibility to depression. The potential for epistatic, epigenetic, and regulatory RNA interactions with these SNPs is discussed, and future areas of research are recommended.

Applications of Precision Medicine in the Treatment of Psychiatric Disorders: A Literature Review

Background: Scientific understanding of precision medicine is rapidly evolving as new associations are made between genetic variants and tolerance to pharmaceuticals [1]. Although pharmacogenetic testing and guidelines exist for many medications, there is limited clinical application of these technologies in part due to limitations of the evidence supporting its use in psychiatric treatment as well as lack of awareness by providers and patients [2]. This narrative literature review aims to assess and summarize the past decade of research in the field of psychiatric pharmacogenetics. Specifically, it will focus on the relationship between antidepressant/antipsychotic drug responses and polymorphisms in nine commonly studied genes: CYP1A2, CYP2B6, CYP2C19, CYP2D6, CYP3A4, CYP3A5, SLC6A4, HTR2A, and DRD2. Methods: Literature from PubMed and Embase that was published between the years 2010 and 2020 was found using strategic keywords and search phrases. Each study represented was a randomized controlled trial or clinical trial tested in adults over the age of eighteen. Results: Of the six CYP450 enzymes that were evaluated, all displayed impacts on the metabolism of psychiatric drugs except CYP3A4, although only one polymorphism (*1B) was included in analysis of that particular gene. Inconclusive results were discovered regarding SLC6A4 5-HTTLPR polymorphisms and further review should be done to determine its relationship with SSRI response. Additionally, review of literature pertaining to DRD2 showed unsubstantial evidence, as four out of seven articles found no connection between treatment or adverse drug reactions (ADR) associated with DRD2. In contrast, influential findings were documented by literature concerning HTR2A polymorphisms and therapeutic consequences and the evidence collected on benefits of pharmacogenomic testing supports the implementation of testing to guide psychiatric treatment with confidence that use may result in fewer failed trials prior to response or remission. Conclusion: Many polymorphic mutations have a significant impact on individual responses to psychiatric treatment and implementation of pharmacogenomic testing in a clinic setting may be beneficial to psychiatric patients. Further review of polymorphic relationships should be done, especially in the case of SLC6A4 and DRD2 variations.

Factors associated with orthodontic pain.

BackgroundPain experienced at teeth during orthodontic treatment varies largely over time, with the reasons for its interindividual variability being largely unknown: age, sex, clinical activations, psychosocial factors and genetic polymorphisms of candidate genes are putative factors that may account to explain this variability. We aimed to investigate the effect of clinical, demographic, psychological and genetic factors on pain levels experienced during fixed orthodontic treatment.MethodsA convenience sample of 183 patients undergoing full‐fixed orthodontic treatment were recruited. Participant's pain levels were assessed seven times over a three‐day period via a smartphone app. Clinical, demographic and psychological data were collected via questionnaires. This included the Pain Catastrophising Scale (Child version), the Corah Dental Anxiety Scale and the State and Trait Anxiety Inventory. Participants provided a DNA sample either in the form of blood or saliva, which were used for genotyping COMT gene rs6269, rs4680, rs4646310, NR3C1 gene rs2963155 and the HTR2A gene rs9316233.ResultsBond ups had the greatest influence on perceived levels of pain experienced on teeth during orthodontic treatment, accounting for over 20% of total variance in pain response. High‐pain responders had higher scores on pain catastrophising (magnification subscale). Self‐reported pain during fixed orthodontic treatment was not influenced by sex, age, time into treatment, anxiety, nor by polymorphisms of COMT, HTR2A or NR3C1 genes.ConclusionsPain on teeth resulting from orthodontic fixed appliances is stronger during bonds‐up and in patients with high catastrophising scores. Demographics, type of clinical activations and the genetic polymorphisms investigated in this research had little or no impact on perceived pain levels.

Serotonergic receptor gene polymorphism and response to selective serotonin reuptake inhibitors in ethnic Malay patients with first episode of major depressive disorder.

The polymorphisms of the 5HTR1A and 5HTR2A receptor genes (rs6295C/G and rs6311G/A) have been evaluated for association with SSRI treatment outcome in various populations with different results. The present study was carried out to determine the association between genotypes of HTR1A-rs6295 and HTR2A-rs6311 with SSRI treatment outcome among the ethnic Malay patients diagnosed with first-episode major depressive disorder (MDD). The patients were recruited from four tertiary hospitals in the Klang Valley region of Malaysia. Predefined efficacy phenotypes based on 25% (partial early response) and 50% (clinical efficacy response) reduction in Montgomery Asberg Depression Rating Scale-self Rated score (MADRS-S) were adopted for assessment of treatment efficacy in this study. Self-reporting for adverse effects (AE) was documented using the Patient Rated Inventory of Side Effect (PRISE) after treatment with SSRI for up to 6 weeks. Adjusted binary logistic regression between genotypes of the polymorphism obtained using sequencing technique with the treatment outcome phenotypes was performed. The 142 patients recruited were made up of 96 females (67.6%) and 46 males (32.4%). Clinical efficacy and Partial early response phenotypes were not significantly associated with genotypes of HTR1A and HTR2A polymorphism. The GG genotype of HTR2A polymorphism has decreased odds for dizziness (CNS) and increased odds for poor concentration. The GA genotype increases the odd for excessive sweating, diarrhoea, constipation and blurred vision. The CC genotype of HTR1A-rs6295 decreases the odd for nausea/vomiting and increases the odd for anxiety. Thus, some genotypes of HTR1A and HTR2A polymorphism were associated with SSRI treatment outcomes in ethnic Malay MDD patients.