Polymorphism Rs4680 Research Articles

Association study of BDNF Val66Met gene polymorphism with bipolar disorder and lithium treatment response in Indian population.

The association of the Val66Met (rs6265) polymorphism in the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder (BD) and response to lithium treatment has been suggested, though inconsistently. The considerable diversity of allele frequency across different populations contributes to this. There is no data from South Asia till date. Hence, we examined the association of this polymorphism in BD cases from India, and its association with lithium treatment response. BD patients (N = 301) were recruited from the clinical services of National Institute of Mental Health and Neurosciences (NIMHANS), India. Lithium treatment response for 190 BD subjects was assessed using Alda scale by NIMH life charts. Patients with total score ⩾7 were defined as lithium responders (N = 115) and patients with score <7 were defined as lithium non-responders (N = 75). Healthy controls (N = 484) with no lifetime history of neuropsychiatric illness or a family history of mental illness were recruited as control set. Genotyping was performed by TaqMan genotyping assay. Genotype and allele frequency of BDNF Val66Met SNP was significantly different (χ2 = 7.78, p = 0.02) in cases compared to controls, and the Val(G) allele was more frequent (χ2 = 7.08, p = 0.008) in BD patients. However, no significant difference is noted in genotype or allele frequencies of this polymorphism between the lithium responders and non-responders. The Val(G) allele of BDNF Val66Met polymorphism is associated with risk of BD in this sample, but it is not related to response to lithium.

The relationship between job stress and job burnout moderated by BDNF rs6265 polymorphism

Job stress can lead to job burnout, and BDNF polymorphism has been found to be involved in its psychopathological mechanism. Research needs a better understanding of the important role of gene × environment (i.e., BDNF polymorphism × job stress) interaction on job burnout. This study aimed to explore how BDNF rs6265 polymorphism may moderate the relationship between job stress and job burnout. Three hundred forty-one healthy participants (187 males and 154 females) from a Chinese university were included. The present study used a standardized questionnaire including demographic characteristics, job stress assessed by the House and Rizzo's Work Stress Scale, and job burnout assessed by the Maslach Burnout Inventory-General Survey. The BDNF rs6265 polymorphism was genotyped. Job stress showed a positive correlation with emotional exhaustion (p < 0.001), cynicism (p < 0.001), and reduced personal accomplishment (p < 0.01). The main effects of BDNF rs6265 polymorphism on emotional exhaustion and cynicism were significant [F(1,333) = 5.136, p = 0.024; F(1,333) = 4.175, p = 0.042, respectively]. The interaction between job stress and BDNF rs6265 on cynicism was significant (△ R2 = 0.013, p = 0.014) after controlling for age, sex, education, and position, indicating that individuals with BDNF rs6265 TT genotype showed higher level of cynicism when in high job stress. The results provided evidence for the association of BDNF gene rs6265 polymorphism, job stress, and their interaction with job burnout. Individuals with TT genotype in BDNF rs6265 might be susceptible to stressful situations, which would lead to cynicism.

The Straw That Broke the Camel's Back: Natural Variations in 17β-Estradiol and COMT-Val158Met Genotype Interact in the Modulation of Model-Free and Model-Based Control.

The sex hormone estradiol has recently gained attention in human decision-making research. Animal studies have already shown that estradiol promotes dopaminergic transmission and thus supports reward-seeking behavior and aspects of addiction. In humans, natural variations of estradiol across the menstrual cycle modulate the ability to learn from direct performance feedback (“model-free” learning). However, it remains unclear whether estradiol also influences more complex “model-based” contributions to reinforcement learning. Here, 41 women were tested twice – in the low and high estradiol state of the follicular phase of their menstrual cycle – with a Two-Step decision task designed to separate model-free from model-based learning. The results showed that in the high estradiol state women relied more heavily on model-free learning, and accomplished reduced performance gains, particularly during the more volatile periods of the task that demanded increased learning effort. In contrast, model-based control remained unaltered by the influence of hormonal state across the group. Yet, when accounting for individual differences in the genetic proxy of the COMT-Val158Met polymorphism (rs4680), we observed that only the participants homozygote for the methionine allele (n = 12; with putatively higher prefrontal dopamine) experienced a decline in model-based control when facing volatile reward probabilities. This group also showed the increase in suboptimal model-free control, while the carriers of the valine allele remained unaffected by the rise in endogenous estradiol. Taken together, these preliminary findings suggest that endogenous estradiol may affect the balance between model-based and model-free control, and particularly so in women with a high prefrontal baseline dopamine capacity and in situations of increased environmental volatility.

Sex-Based Differences in Cardiac Gene Expression and Function in BDNF Val66Met Mice.

Brain-derived neurotrophic factor (BDNF) is a pleiotropic neuronal growth and survival factor that is indispensable in the brain, as well as in multiple other tissues and organs, including the cardiovascular system. In approximately 30% of the general population, BDNF harbors a nonsynonymous single nucleotide polymorphism that may be associated with cardiometabolic disorders, coronary artery disease, and Duchenne muscular dystrophy cardiomyopathy. We recently showed that transgenic mice with the human BDNF rs6265 polymorphism (Val66Met) exhibit altered cardiac function, and that cardiomyocytes isolated from these mice are also less contractile. To identify the underlying mechanisms involved, we compared cardiac function by echocardiography and performed deep sequencing of RNA extracted from whole hearts of all three genotypes (Val/Val, Val/Met, and Met/Met) of both male and female Val66Met mice. We found female-specific cardiac alterations in both heterozygous and homozygous carriers, including increased systolic (26.8%, p = 0.047) and diastolic diameters (14.9%, p = 0.022), increased systolic (57.9%, p = 0.039) and diastolic volumes (32.7%, p = 0.026), and increased stroke volume (25.9%, p = 0.033), with preserved ejection fraction and fractional shortening. Both males and females exhibited lower heart rates, but this change was more pronounced in female mice than in males. Consistent with phenotypic observations, the gene encoding SERCA2 (Atp2a2) was reduced in homozygous Met/Met mice but more profoundly in females compared to males. Enriched functions in females with the Met allele included cardiac hypertrophy in response to stress, with down-regulation of the gene encoding titin (Tcap) and upregulation of BNP (Nppb), in line with altered cardiac functional parameters. Homozygous male mice on the other hand exhibited an inflammatory profile characterized by interferon-γ (IFN-γ)-mediated Th1 immune responses. These results provide evidence for sex-based differences in how the BDNF polymorphism modifies cardiac physiology, including female-specific alterations of cardiac-specific transcripts and male-specific activation of inflammatory targets.

Elevation of DNA Methylation in the Promoter Regions of the Brain-Derived Neurotrophic Factor Gene is Associated with Heroin Addiction.

To study the potential role of brain-derived neurotrophic factor (BDNF) methylation in heroin addiction, we first detected the methylation level of seven CpG islands that included 106 CpG sites in the promoter regions of BDNF from 120 people addicted to heroin and 113 controls. Methylation quantitative trait locus (mQTL) analysis was then employed to determine the association between the single-nucleotide polymorphism rs6265, a well-known locus shown to be correlated with heroin addiction, and the methylation levels of these CpG sites. Finally, we used the JASPAR database to predict whether transcription factors could bind to these CpG sites. We found that the methylation levels of CpG islands 6 and 7 and the methylation levels of BDNF_45 and BDNF_80 were significantly higher in the heroin addiction group than in the control group. We also found that rs6265 was an mQTL and was associated with the methylation level of BDNF_58. Using the JASPAR database, we found that ALX homeobox 3 (ALX3), achaete-scute family bHLH transcription factor 1 (ASCL1) and aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) could bind to CpG island 6, and ALX3 could bind to CpG island 7. In summary, we showed that increased DNA methylation in the promoter regions of the BDNF gene was associated with heroin addiction in Han Chinese.

The impact of CPT1B rs470117, LEPR rs1137101 and BDNF rs6265 polymorphisms on the risk of developing obesity in an Italian population

ObjectiveThis study aimed to analyze 11 single nucleotide polymorphisms (SNPs) belonging to 9 genes involved in metabolic pathways (BDNF rs6265; PNPLA3 rs2294918 and rs2076212; CIDEA rs11545881; NTRK2 rs2289658; ALOX12 rs1126667; ALOX12B rs2304908; LEPR rs1137101; CPT1B rs470117 and rs8142477; rs2305507 CPT1A) in obese patients and controls. MethodsPolymorphisms were analyzed in 300 severe obese patients undergoing bariatric surgery (body mass index >30 kg/m2) and 404 control subjects in order to evaluate their association with obesity and clinical variables. ResultsOur findings showed significant differences for the allelic distributions of CPT1B rs470117 and LEPR rs11371010 in obese subjects compared to controls. The BDNF rs6265 correlates with obesity only when associated with the other two SNPs. In particular, for CPT1B rs470117 and LEPR rs1137101, the rare allele was associated with a reduced risk of developing the obese phenotype, whereas the simultaneous presence of the common C allele for rs470117 and A allele for rs1137101 was more frequent in obese patients (p = 0.002, OR = 1.417). A significant association between CPT1B rs470117 and steatosis was found. Moreover, we observed that by associating the rare allele T of the BDNF rs6265 with the most common alleles of the SNPs CPT1B rs470117 and LEPR rs1137101, the combination of T-C-A alleles was associated with a higher risk of developing an obese phenotype (p = 0.001, OR = 1.6679). ConclusionsOur results suggest that SNPs CPT1B rs470117 and LEPR rs1137101 taken individually and in association with BDNF rs6265 may be involved in an increased risk of developing obese phenotype in an Italian cohort.

COMT rs4680 single nucleotide polymorphism, ethnicity, and age are associated with fibromyalgia in women

To investigate the influence of the catechol-O-methyltransferase enzyme (COMT) single nucleotide polymorphism (SNP) rs4680 (G/A) on fibromyalgia in women. In this observational study of case-control type 29 women with a diagnosis of FM (cases) and 31 healthy non-fibromyalgia women (controls). Sociodemographic and anthropometric data were collected, as well as data relating to Symptom Severity Scale and Generalized Pain Index and peripheral blood samples for DNA extraction; genotypic analyzes were performed by PCR-SSP. We observed that rs4680 AA genotype was more frequently observed in fibromyalgia than controls (p=0.02). The A allele was also more often present in the fibromyalgia participants than in their control peers (p = 0.03). There was a statistically significant association between race and FM sufferers, showing that those of white ethnicity had a 2.05 times greater chance of developing the syndrome than non-white individuals (p=0.03; CI 95% 0.93 – 4.53). A statistically significant correlation between age and FM was observed (rS=0.812, p=0.01). This study demonstrates that white women above the age of 45, who have the AA genotype or A-allele, presents a higher risk of developing FM, showing that this polymorphism of the COMT gene may be one of the risk factors for the fibromyalgia.

The prevalence of the Val66Met polymorphism in musicians: Possible evidence for compensatory neuroplasticity from a pilot study.

The study compared the prevalence of the Val66Met Brain-derived Neurotrophic Factor single nucleotide polymorphism (rs6265) in a sample of musicians (N = 50) to an ethnically matched general population sample from the 1000 Human Genome Project (N = 424). Met-carriers of the polymorphism (Val/Met and Met/Met genotypes) are typically present in 25–30% of the general population and have associated deficits in motor learning and plasticity. Many studies have assessed the benefits of long-term music training for neuroplasticity and motor learning. This study takes a unique genetic approach investigating if the prevalence of the Val66Met BDNF polymorphism, which negatively affects motor learning, is significantly different in musicians from the general population. Our genotype and allele frequency analyses revealed that the distribution of the Val66Met polymorphism was not significantly different in musicians versus the general population (p = 0.6447 for genotype analysis and p = 0.8513 allele analysis). In the Musician sample (N = 50), the prevalence of the Val/Met genotype was 40% and the prevalence of the Met/Met genotype was 2%. In the 1000 Human Genome Project subset (N = 424), the prevalence of Val/Met was 33.25% and the Met/Met genotype prevalence was 4%. Therefore, musicians do exist with the Val66Met polymorphism and the characteristics of long-term music training may compensate for genetic predisposition to motor learning deficits. Since the polymorphism has significant implications for stroke rehabilitation, future studies may consider the implications of the polymorphism in music-based interventions such as Neurologic Music Therapy.

Oxytocin receptor gene polymorphism and low serum oxytocin level are associated with hyperphagia and obesity in adolescents.

In recent years, oxytocin (OXT) and polymorphisms in the oxytocin receptor (OXTR) gene have been reported to play roles in obesity pathogenesis. However, there was no study evaluating OXTR gene variants in childhood obesity. The aim of the study was to investigate the relation of OXTR gene polymorphisms and serum OXT levels with metabolic and anthropometric parameters in obese and healthy adolescents. The study was a multi-centered case-control study, which was conducted on obese and healthy adolescents aged between 12 and 17 years. Serum OXT and leptin levels were measured, and OXTR gene variants were studied by qPCR (rs53576) and RFLP (rs2254298) methods. A total of 250 obese and 250 healthy adolescents were included in this study. In the obese group, serum OXT level was lower and leptin level was higher than the control group. In the obese group, frequencies of homozygous mutant (G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were higher than the control group. Homozygous mutant(G/G) and heterozygous (A/G) genotypes for rs53576 polymorphism were found to increase the risk of obesity compared to the wild type (A/A) genotype [OR = 6.05 and OR = 3.06; p < 0.001, respectively]. In patients with homozygous mutant (G/G) and heterozygous (A/G) genotype for rs53576 polymorphism, serum OXT levels were lower than the wild type (A/A) genotype. In the obese group, hyperphagia score was higher than the control group and correlated negatively with serum OXT level. This study revealed that low serum OXT level, which is associated with hyperphagia may be an underlying cause for obesity in adolescents. For rs53576 polymorphism of the OXTR gene, obesity risk is higher in patients with homozygous mutant(G/G) and heterozygous(A/G)genotypes.

The DRD2 Taq1A polymorphism moderates the effect of PTSD symptom severity on the left hippocampal CA3 volume: a pilot study

Rationale and objectivesThe hippocampus, especially the CA1, CA3, and dentate gyrus (DG) subfields, is reported to be associated with post-traumatic stress disorder (PTSD) after trauma. However, neuroimaging studies of the associations between PTSD and hippocampal subfield volumes have failed to yield consistent findings. The aim of this study is to examine whether the dopamine D2 receptor (DRD2) Taq1A polymorphism, which is associated with both hippocampal function and PTSD, moderated the association between PTSD severity and hippocampal CA1, CA3 and DG volumes.MethodsT1-weighted images were acquired from 142 trauma survivors from the 2008 Wenchuan earthquake using a 3.0-T magnetic resonance imaging system. Hippocampal subfield segmentations were performed with FreeSurfer v6.0. We used the simple moderation model from the PROCESS v3.4 tool for SPSS 23.0 to examine the association between the rs1800497 polymorphism, PTSD severity, and hippocampal CA3 and DG volumes.ResultsA significant genotype × PTSD symptom severity interaction was found for the left CA3 volume (ΔF = 5.01, p = 0.008, ΔR2 = 0.05). Post hoc, exploratory analyses deconstructing the interaction revealed that severe PTSD symptomatology were associated with reduced left CA3 volume among TC heterozygotes (t = − 2.86, p = 0.005).ConclusionsThis study suggests that DRD2 Taq1A polymorphism moderates the association between PTSD symptomatology and left CA3 volume, which promotes an etiological understanding of the hippocampal atrophy at the subfield level. This highlights the complex effect of environmental stress, and provides possible mechanism for the relationship between the dopaminergic system and hippocampal function in PTSD.

Association between brain-derived neurotropic factor gene variant (rs6265; C > T) and schizophrenia, its psychopathology and intelligence

Background and objectivesThe etiology of schizophrenia (SCZ) is not yet known, but the genetic factor has an essential role. Its heritability is estimated up to 85 percent. This study aimed to determine whether the selected brain-derived neurotropic factor (BDNF) gene variant (rs6265) is associated with SCZ, its psychopathology and intelligence quotient (IQ). MethodsRs6265 was genotyped in 159 participants, including 71 unrelated patients with SCZ (males = 40 [56%]) and 88 healthy controls (males = 35 [40%]). Psychopathology assessment was done by using positive and negative symptoms scale (PANSS), and IQ was measured by Wechsler adult intelligence scale (WAIS). COCAPHASE and CLUMP22 softwares were used to compare allele and genotype frequencies respectively. Two-way multivariate ANOVA was done using SPSS22 to evaluate the effects of the group (patients and healthy control) and the genotype on the test scores, including PANSS and WAIS scores, considering sex and smoking status as covariates. ResultsThe study showed that the BDNF rs6265 C allele and CC genotypes, psychopathology, including PANSS scores, and also IQ were significantly different in all, male and female patients compared to healthy participants. For rs6265, we found significantly higher frequencies of the C allele (P = 0.04) in all participants with SCZ.The findings also revealed that BDNF polymorphism (rs6265) increased significantly the risk of SCZ in different genetic models. ConclusionThe results showed that the BDNF rs6265 may be associated with the risk of SCZ development in an Iranian group of patients with SCZ. These results may be helpful in better understanding the role of the BDNF gene in the pathogenesis of the disorder.

Associations of the MAOA uVNTR genotype and 5-HTTLPR/rs25531 haplotype with psychopathic traits

Previous studies have linked polymorphisms of the monoamine oxidase A (MAOA uVNTR) and serotonin transporter gene (5-HTTLPR) to individual differences in the expression of psychopathic traits, but findings remain inconsistent. One possible reason is that these studies have treated psychopathy as a unitary construct when there is accumulating evidence that there are variants or subtypes. We used a variable-centered and a person-centered approach by (a) examining putative genetic correlates of psychopathy across individuals and (b) comparing the frequencies of the MAOA uVNTR genotype and 5-HTTLPR/rs25531 haplotype between empirically derived subtypes of psychopathy, respectively. Notably, we included the often neglected rs25531 polymorphism, which is closely connected to the 5-HTTLPR. Based on data from male offenders and community volunteers, structural equation modeling indicated that the 5-HTTLPR/rs25531 haplotype was specifically associated with interpersonal deficits beyond the overarching psychopathy construct. Latent profile analysis revealed four clusters that were labeled non-psychopaths, sociopaths, callous-conning, and psychopaths. The low-activity variant of the 5-HTTLPR/rs25531 haplotype was significantly more frequent in the callous-conning compared to the non-psychopathic subtype. There were no effects for the MAOA uVNTR. The results illustrate that psychopathy should not be treated as a unitary construct but that there are variants with specific profiles of psychopathic traits, and that the 5-HTTLPR/rs25531 haplotype plays a role in the manifestation of interpersonal deficits from a variable-centered as well as from a person-centered view.

Rs1344706 polymorphism of zinc finger protein 804a (ZNF804a) gene related to the integrity of white matter fiber bundle in schizophrenics.

Genetic factors play an important role in the pathogenesis of schizophrenia (SZ), and the zinc finger protein 804a (ZNF804a) gene has been considered to be a risk gene for schizophrenia. In the present study, the correlation between rs1344706 polymorphism of ZNF804a gene and the integrity of white matter in schizophrenic cases was explored. A total of 60 SZ patients and 100 healthy controls (HC) were included to undergo head MRI. According to the genotyping of rs1344706 in ZNF804a, the subjects in each group were divided into a normal allele and risk allele-carrying group. The imaging data were preprocessed by PANDA software, and thefractional anisotropy (FA) of each subject was calculated. With SPM8 software, age and years of education were considered as covariates, and diagnosis as well as genotype (AA, GG/AG) were considered as intergroup factors. Four groups of FA images were analyzed by two-factor analysis of variance. The FA value of the right posterior radiocrown in the patient group was lower than that in the control group, and the difference was statistically significant. The FA value of the right lower frontal occipital tract and the right upper radiocrown in the G allele carrier group was lower than that in the A allele homozygous group. There was detection of an interaction between the FA value of the splenium of corpus callosum, the body part of the corpus callosum and the right cingulate tract. In the present study, it was demonstrated that the rs1344706 GG/AG genotype of the ZNF804a gene locus in SZ patients suffered from abnormal structure in a specific region of the brain. This finding indicated that the rs1344706 single nucleotide polymorphism of the ZNF804a gene may affect the integrity of the white matter of the brain in SZ patients and may be involved in the pathophysiological mechanism of SZ.

Both AA genotype of rs165599 and Val/Val genotype of rs4680 in COMT are associated with an increased risk of recurrence of prostate cancer

IntroductionCOMT expression was reported to be associated with the recurrence of prostate cancer. Furthermore, it has been shown that rs165599 SNP in the 3’UTR of COMT affects the interaction between miR-138 and COMT, while another polymorphism (rs4680) located in the gene of COMT also affects its expression. Here, we explored the combined effect of rs165599 and rs4680 .Material and methodsKaplan-Meier analysis was performed to analyze the PSA-progression-free survival of prostate cancer patients carrying different genotypes of rs165599 and rs4680 SNPs. IHC and Western blot were used to evaluate the expression of COMT. Real-time PCR was carried out to examine the expression of miR-138 and COMT mRNA. Luciferase assay was performed to explore the inhibitory role of miR-138 in the expression of COMT carrying different genotypes.ResultsThe PSA-progression-free survival was significantly increased in prostate cancer patients carrying the rs165599-AA + rs4680-Val/Val genotype. In concordance with this, the expression of COMT was remarkably elevated in the tissue samples collected from prostate cancer patients carrying the rs165599-AA + rs4680-Val/Val genotype. Luciferase assay demonstrated that COMT-G at rs165599 was effectively suppressed by miR-138 through binding to the 3’ UTR of COMT-G. Furthermore, COMT expression was notably suppressed by miR-138 precursors in primary prostate cancer cells carrying GG genotype at rs165599.ConclusionsThe findings of this study demonstrated that the carriers of AA genotype of rs165599 and Val/Val genotype of rs4680 showed an increased risk of prostate cancer recurrence, and these two polymorphisms may jointly function as a novel biomarker for the prognosis of prostate cancer recurrence.

An independent, replicable, functional and significant risk variant block at intron 3 of CACNA1C for schizophrenia.

Genome-wide association studies have identified a significant risk gene, CACNA1C, for schizophrenia. In this study, we comprehensively investigated a large set of CACNA1C single-nucleotide polymorphisms (SNPs) to identify the replicable risk alleles for schizophrenia and explore their biological functions. One Jewish (1044 cases vs 2052 controls), one European (1350 cases vs 1378 controls) and one exploratory African American samples (98 cases vs 20 controls) were analyzed to identify replicable single-nucleotide polymorphism-schizophrenia associations. The regulatory effects of risk alleles on CACNA1C messenger RNA expression were examined. The most robust risk tagSNP (rs1006737) was meta-analyzed on 17 studies (74,122 cases vs 109,062 controls), and associated with the gray matter volumes of seven subcortical structures in 38,258 Europeans, and the surface areas and thickness of 34 cortical regions in 33,992 Europeans and 2944 non-Europeans. Forty-seven replicable risk single-nucleotide polymorphisms, including a 20-single-nucleotide polymorphism haplotype block, were identified in our samples (1.8 × 10-4 ⩽ p ⩽ 0.049). This variant block was consistently associated with schizophrenia across four independent Psychiatric Genomics Consortium cohorts (79,645 cases vs 109,590 controls; 2.5 × 10-17 ⩽ p ⩽ 0.017). This block showed significant expression quantitative trait loci in three independent European brain cohorts (5.1 × 10-12 ⩽ p ⩽ 8.3 × 10-3) and could be tagged by the most significant risk single-nucleotide polymorphism rs1006737. The minor allele A of rs1006737 significantly increased risk for schizophrenia across the Jewish and European samples (p = 0.029 and 0.004, respectively), and this association was highly significant in the meta-analysis (p = 1.62 × 10-42). This allele also significantly altered the CACNA1C messenger RNA expression in five brain regions (5.1 × 10-12 ⩽ p ⩽ 0.05), decreased the gray matter volume of thalamus (p = 0.010), the surface area of isthmus cingulate cortex (p = 0.013) and the thickness of transverse temporal and superior temporal sulcus cortexes (0.005 ⩽ p ⩽ 0.043). We identified an independent, replicable, functional, and significant risk variant block at CACNA1C for schizophrenia, which could be tagged by the most robust risk marker rs1006737, suggesting an important role of CACNA1C in the pathogenesis of schizophrenia.

Moderators for the association between genotypes of the HTR1A ‐rs6295 or HTR2A ‐rs6311 polymorphisms and efficacy of SSRI treatment among the patients of Malay ethnic group

Background Major depressive disorder (MDD) has high level of morbidity. It shows great inter-individual difference in treatment responses and a complete absence of reliable biomarkers. Hypothesis The evaluations between genotypes of HTR1A-rs6295 or HTR2A-rs6311 with clinical treatment efficacy response (CTER) based on clinical and sociodemographic features can unravel a significant association result. Aim To identify moderators for the association between CTER with genotypes of HTR1A-rs6295 or HTR2A-rs6311 in a population of Malay MDD patients. Objectives 1. To determine the association between genotypes of HTR1A-rs6295 or HTR2A-rs6311 with CTER when patients are categorized based on their history of chronic disease and family history of psychiatric illness 2. To determine the association between genotypes of HTR1A-rs6295 or HTR2A-rs6311 with CTER when patients are categorized based on the presence or absence of a number of personality trait types. 3. To determine the association between genotypes of HTR1A-rs6295 or HTR2A-rs6311 with CTER when patients are categorized based on key socio-demographic features. Methodology Ethical approval from appropriate authorities (NMRR-14-688-19696) and informed consent from the MDD patients were obtained before recruitment. Patient were recruited over 2 years and provided blood for genotyping of the HTR1A-rs6295 and HTR2A-rs6311. Clinical features, socio-demography, responses to Montogemery Asberg depression rating scale-self (MADRS-S) and Temperament /Personality questionnaires were obtained. Appropriate statistics for the association of the genotypes and CTER based on individual socio-demographic and clinical features was done. Result The 142 patients were Muslims (100%), young (median age = 31.50 years), females (67.6%) and low income earners (62.7%). Patients carrying the CG+GG genotype of the HTR1A-rs6295 who have effectiveness (not the self-criticism traits) had significantly lower odd (P = 0.016, OR = 0.099 (0.011 – 0.860)) for clinical treatment efficacy response (CTER). A Similar result in patients carrying the GG genotype of the HTR1A-rs6295 polymorphism who do not have anxious-worrying, social avoidance, inter-personal sensitivity, effectiveness, cooperativeness, perfectionism and irritability. Unmarried patients with the GG-HTR1A-rs6295 genotype have a significantly lower odd P = 0.029 (OR = 0.126 (CI = 0.015 -1.058)) for CTER . Low income earners who have the CC-HTR1A-rs6295 have higher odd for CTER. Failure of CTER was significantly more among patients who have no history of any chronic disease and possess the HTR1A-rs6295-GG or HTR2A-rs6311-GA genotypes. Conclusion The association of the genotypes of HTR1A-rs6295 or HTR2A-rs6311 polymorphism with CTER was observed in patients who were married, of low income earning, diagnosed with a chronic disease and have some key personality traits with the exception of effectiveness trait.

The influence of rs53576 polymorphism in the oxytocin receptor (OXTR) gene on empathy in healthy adults by subtype and ethnicity: a systematic review and meta-analysis.

Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (OXTR), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically cognitive empathy (CE) and affective empathy (AE), in healthy adults. Twenty cohorts of 8933 participants aged 18-98 were identified, including data from the Sydney Memory and Ageing Study, a cohort of older community adults. Meta-analyses found G homozygotes had greater generalized empathic abilities only in young to middle-aged adults. While meta-analyses of empathy subdomains yielded no significant overall effects, there were differential effects based on ethnicity. G homozygotes were associated with greater CE abilities in Asian cohorts (standardized mean difference; SMD: 0.09 [2.8·10-3-0.18]), and greater AE performance in European cohorts [SMD: 0.12 (0.04-0.21)]. The current literature highlights a need for further work that distinguishes between genetic and ethnocultural effects and explores effects of advanced age on this relationship.

Association of polymorphic marker Val158Met of COMT gene with depression in an open population 25–44 years old (WHO international program MONICA, epidemiological study)

Objective : to investigate the association of the polymorphic marker Val158Met in the catechol-O-methyl transferase (COMT) gene with depression in an open population aged 25–44 years. Patients and methods . A representative sample of the population living in Oktjabr'skij district of Novosibirsk aged 25– 44 years (427 men, median age – 34±0.4 years, response rate – 71%; 548 women, median age 35±0.4 years, response rate – 72%) was screened in 2013–2016 (budget framework № 0324- 2018-0001, Reg. № AAAA-A17-117112850280-2). In addition to the standard epidemiological examination, screening participants underwent psychological testing, which determined the level of depression. Study participants who underwent COMT Val158Met (rs4680) polymorphism genotyping were randomly assigned to a cohort of 224 men and 217 women. Pearson's χ2 test was used to test the statistical significance of differences between these groups; p≤0.05 was considered statistically significant in all types of analysis. Results and discussion . In an open population aged 25–44 years, the prevalence of severe depression (SD) was 13.2%, moderate depression – 24.4%. SD was more prevalent in COMT G/G genotype carriers (61.8%), compared to A/A genotype carriers (38.2%; χ 2 =6.097; df=2, p=0.047); the G allele carriers also had a higher prevalence of SD (55.3%), compared to A allele carries (44.7%; χ 2 =5.408; df=1; p=0.02). SD was less prevalent among male COMT A/A genotype carriers (15.8%), compared to G/A genotype carriers (84.2%; χ 2 =4.603; df=1; p=0.032). SD was more prevalent in female G/G genotype carriers (65.5%), compared to A/A genotype carriers (34.5%; χ 2 =4.769; df=1; p=0.029). The G allele was more common among women with SD (58.2%) than the A allele (41.8%; χ 2 =6.658; df=2; p=0.01). In a logistic regression model, COMT Val/Val genotype in the studied population [Relative risk (RR) 1.594], as well as G (Val) allele in the studied population (RR=1.378) and women (RR=1.557), significantly increased the risk of depression. Conclusion. The data allows us to assume that COMT G/G polymorphism may be linked to a high depression level.

Serum Levels of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Elite Athletes: Potential Markers of the Use of Transcranial Direct Current Stimulation in Sport.

Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation that may enhance mental and physical performance in sports, representing a potential new form of doping (“brain doping” or “electromagnetic doping”). This study aims to identify diagnostic biomarkers for detecting the possible abuse of tDCS in sport. Brain-Derived Neurotrophic Factor (BDNF) and other neurotrophins (NT, such as beta nerve growth factor, NGF) were pre-selected as potential candidates since their serum values have been observed to change following tDCS. Neurotrophins were measured using ELISA assays in 92 serum samples collected from elite athletes, classified by sex (males = 74; females = 18), age (range 17–25 n = 27, 26–35 n = 36, and over 35 n = 14; age not known n = 15), type of sports practiced (endurance n = 74; power n = 18), and type of sample collection (“in competition” n = 24; “out of competition” n = 68). Single nucleotide polymorphisms (rs6265, rs11030099, and rs11030100) were genotyped on 88 samples to determine their influence on the analytes' basal levels. Athletes older than 35 presented higher BDNF values than younger individuals (p < 0.05). Samples collected “in competition” showed higher BDNF concentrations than those collected “out of competition” (p < 0.05). The studied polymorphisms appeared to affect only on proBDNF, not altering BDNF serum concentrations. NT-3 and NT-4 were poorly detectable in serum. Our results suggest that BDNF can be considered as a first biomarker to detect the abuse of tDCS in sport doping. Further studies are necessary to assess whether proBDNF and beta NGF can also be considered suitable biomarkers to detect the recourse to electromagnetic brain stimulation in sports, especially in the case their serum levels can be monitored longitudinally. To the best of our knowledge, this is the first study aimed to pre-select serum biomarkers to identify the use of tDCS, and represents the first step toward the development of an indirect strategy, preferably based on the longitudinal monitoring of individual data, for the future detection of “brain doping” in sports.

The role of childhood trauma, HPA axis reactivity and FKBP5 genotype on cognition in healthy individuals

Cognitive impairment has been associated with both childhood adversity and abnormalities of hypothalamic-pituitary-adrenal (HPA) axis function. An interaction exists between the functional polymorphism rs1360780 in the FKBP5 gene and childhood maltreatment, influencing a variety of clinical outcomes. Our goal was to study the relationship between different types of childhood trauma, HPA axis functionality, rs1360780 genotype and cognitive function in 198 healthy individuals who participated in the study. We obtained clinical data, childhood maltreatment scores and neurocognitive performance by clinical assessment; HPA negative feedback was analysed using the dexamethasone suppression test ratio (DSTR) after administration of 0.25 mg of dexamethasone; and the FKBP5 rs1360780 polymorphism was genotyped in DNA obtained from blood samples. The results showed a significant influence of physical neglect on measures of neurocognition as well as an interaction between the DSTR and physical and emotional neglect. Regarding social cognition, a significant association was found with sexual and physical abuse as well as with rs1360780 risk-allele carrier status. Moreover, an interaction between the rs1360780 genotype and the presence of physical abuse was significantly associated with social cognition results. Our results suggest a specific impact of different kinds of childhood maltreatment on measures of neurocognition and social cognition, which might be influenced by HPA axis reactivity and genetic variants in HPA axis-related genes such as FKBP5. Disentangling the relationship between these elements and their influence on cognitive performance might help identify susceptible individuals with higher stress vulnerability and develop preventive interventions.