5-HTTLPR Polymorphism Research Articles

Functional Connectivity Patterns and the Role of 5-HTTLPR Polymorphism on Network Architecture in Female Patients With Anorexia Nervosa.

IntroductionRecent neuroimaging studies suggest that anorexia nervosa (AN) symptoms emerge from failures in the relationships between spatially distributed networks that support different cognitive, emotional, and somatosensory functions. The 5-HTTLPR genotype has been shown to modulate all these abilities in AN, as well as the connectivity patterns between brain regions that support their functioning. This study aims at exploring the presence of any difference in functional connectome properties between AN patients and healthy controls (HC) by means of graph theory tools. The effect of 5-HTTLPR genotype on regional and global network characteristics in AN and HC was also explored.MethodsA sample of 74 subjects (38 HC, 36 AN) underwent a resting state functional magnetic resonance imaging and was genotyped for 5-HTTLPR polymorphism. Comparisons of network properties were made between the AN and HC groups and, within each group, between 5-HTTLPR carriers of low-functioning alleles and carriers of the long–long genotype.ResultsPatients with AN displayed lower network clustering than HC (p = 0.04 at Mann–Whitney U test). Based on both degree and betweenness, a different distribution of network hubs emerged in the two groups. In particular, the anterior part of the anterior cingulate cortex was a hub only in the patient group. A correlation emerged between differences in brain volumes between patients and HC and differences in degree values of basal ganglia, nodes in the insula, and those in the parietal cortex. Carriers of the short allele of the 5-HTTLPR polymorphism were characterized by lower small-world properties (p = 0.027) and modularity (p = 0.031) in the patient group, and a trend toward higher modularity (p = 0.033) and small-world values (p = 0.123) in the HC group.DiscussionPatients with AN showed differences in hubs distribution, providing evidence of the presence of a different functional architectural backbone in this group. Since some correlation emerged between different degree values of nodes and differences in volumes, further longitudinal studies are warranted to better understand the role of malnutrition on brain network architecture. The opposite effects of 5-HTTLPR polymorphism on global network characteristics in the two groups suggest an interaction of the short allele and malnutrition in modulating brain network properties.

Association between the promoter region of serotonin transporter polymorphisms and recurrent aphthous stomatitis: A meta-analysis

ObjectivesTo assess the association between the promoter region of serotonin transporter (5-HTTLPR) gene polymorphism and recurrent aphthous stomatitis (RAS) occurrence. DesignsWe performed the meta-analysis to determine the potential association between 5-HTTLPR polymorphism and RAS. We retrieved revelant studies from the PubMed, Scopus, Embase, Web of Science and Cochrane Library databases up to January 2019. Data were analyzed for odd ratios with 95% confidence intervals using Revman 5.3 software. ResultsThere were 4 studies in the meta-analysis, which included 291 RAS cases and 286 controls. It indicated a substantially augmented threat of RAS with respect to S vs. L (P = 0.005), SS vs. LL+LS (P ＜ 0.0001) and SS vs. LL models (P ＜ 0.00001), respectively. No heterogeneity was found between studies in all comparisons. ConclusionsThe current meta-analysis provides evidence to prove the association between 5-HTTLPR polymorphism and RAS. Further studies should be performed to clarify the biochemical function and pathological role of 5-HTTLPR in the risk of RAS.

Childhood adversities and 5-HTTLPR polymorphism as risk factors of substance use disorders: retrospective case-control study in Murcia (Spain)

ObjectiveTo explore the separate and joint associations of childhood adversities and 5-HTTLPR polymorphism as risk factors for substance use disorders among adults.DesignRetrospective case-control study.SettingCases from the substance unit and controls...

The 5-HTTLPR polymorphism impacts moral permissibility of impersonal harmful behaviors.

Inspired by the roles of serotonin in an emotional aversion to harmful actions, we examined to what extent serotonin transporter gene (5-HTT)–linked polymorphic region (5-HTTLPR), a proxy for measuring serotonin function, underpinned the individual differences in moral judgment through cross-sectional analysis and two-wave comparison. The cross-sectional analysis with a larger cohort (N = 1197) showed that the SS carriers of the 5-HTTLPR polymorphism, corresponding to the low ratio of serotonin recycling from the synaptic cleft, rated impersonal harmful actions (e.g. flipping a switch to divert a train to hit one person instead of five people) as more permissible as compared with the L-allele carriers. The two-wave comparison with a subsample from the larger cohort (N = 563) indicated that the association between 5-HTTLPR polymorphism and moral permissibility of impersonal harmful actions was stable from wave 1 to wave 2. Thus, these findings highlight the importance of the 5-HTTLPR polymorphism to harmful moral behaviors.

The interaction between estradiol change and the serotonin transporter gene (5-HTTLPR) polymorphism is associated with postpartum depressive symptoms.

Although estrogenic fluctuation is considered a major risk factor for postpartum depression (PPD), the effects of the interactions between the genetic background and estradiol (E2) change on PPD are not well understood. Here, a cohort study with 437 postpartum women was carried out to evaluate the role of a serotonin transporter gene polymorphism (5-HTTLPR) and E2 change on the risk of PPD symptoms. The participants were assessed using the Edinburgh Postnatal Depression Scale and the Self-Rating Depression Scale at 1 and 6 weeks after delivery. The PCR-based restriction fragment length polymorphism method was utilized to examine the genotype distribution of the 5-HTTLPR polymorphism, and the serum levels of E2 were determined in individuals in the third trimester of pregnancy and at 1 week postpartum. A significant association was observed between E2 change and PPD susceptibility in the late postpartum period (6 weeks) [P = 0.002, odds ratio (OR) = 2.341, 95% confidence interval (CI) = 1.361-4.027], but it was not observed in the early postpartum period (1 week). There was no significant association between the 5-HTTLPR genotype and PPD risk at both the early and late postpartum periods (P > 0.05). However, the interaction between E2 change and the 5-HTTLPR polymorphism could reasonably influence PPD risk. The women who carried the SS genotype with large decreases in E2 showed a significantly higher risk for PPD at both the early (P = 0.002, OR = 2.525, 95% CI = 1.384-4.059) and late postpartum periods (P < 0.001, OR = 3.108, 95% CI = 1.562-4.436) compared with those who carried the SL/LL genotype. This study suggests that there is an association between E2 change in the perinatal period with the 5-HTTLPR genotype and the occurrence of PPD.

A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts.

Clinical risk factors for postoperative nausea and vomiting (PONV) are well described, whereas genetic findings are conflicting. The aim of this study was to investigate a possible association of genetic variants and nongenetic variables with the incidence and severity of PONV. A prospective observational study in two independent and different patient cohorts. Two independent patient cohorts differing in surgical procedures were enrolled in two tertiary care hospitals between 2008 and 2016. Consecutive patients of European origin undergoing elective surgery in two university hospitals. Clinical data were collected up to 24 h after surgery, and blood was drawn for genotyping. Of 2773 patients enrolled, 918 (Cohort A) and 1663 (Cohort B) with complete data sets were analysed. Patients were allocated to one of three groups (No PONV, Intermediate PONV or Severe PONV) depending on the frequency of vomiting, the severity of nausea and the need for antiemetics. Clinical variables and 13 genetic variants of seven candidate genes were evaluated for association with these three phenotypes. The cohorts were analysed separately by ordinal logistic regression analysis, treating PONV as a dependent ordinal three-stage variable. Odds ratios (ORs) with 95% confidence intervals were calculated. In Cohort A, the main predictors for PONV were female sex [OR (95% CI): 3.6 (2.7 to 4.8), P < 0.0001], nonsmoking status 1.8 (1.3 to 2.5), P < 0.001, the SS genotype (5-HTTLPR, rs4795541) of the promoter polymorphism in the serotonin transporter 1.5 (1.1 to 2.1), P = 0.019, and patient age 0.99 (0.98 to 0.99), P = 0.013. Analysis of Cohort B was consistent with these findings [5-HTTLPR: 1.8 (1.4 to 2.3), P < 0.00001]. Sex-specific regression models confirmed this 5-HTTLPR association in women and men. In two independent cohorts, in addition to the well known clinical factors, a polymorphism of 5-HTTLPR in the serotonin transporter was independently associated with PONV. A possible evaluation of this biomarker to improve risk prediction within the scope of precision medicine should be considered. Clinicaltrials.gov identifier NCT03490175.

Anxiety-related Endophenotypes and Hazardous Alcohol Use in Young Adults are Associated with a Functional Polymorphism in the SLC6A4 Gene

Background:A functional polymorphism (5-HTTLPR, rs4795541) in the serotonin transporter (SLC6A4) gene has been shown as an important candidate for several psychiatric and behavioral traits.Objective:The objective of this study was to examine the possible interaction of this polymorphism with physical neglect in childhood on the presentation of anxiety traits and hazardous alcohol consumption in young Colombian subjects.Methods:272 young adults (mean age: 21.3 years) were evaluated with the Childhood Trauma Questionnaire, the Zung Self-rating Anxiety Scale, the Big Five Inventory, the Cohen’s Perceived Stress Scale, the Alcohol, Smoking, Substance Involvement Screening Test and the Alcohol Use Disorders Identification Test. Genotyping for the 5-HTTLPR polymorphism was carried out using conventional PCR. A linear regression model, corrected by age and gender, was used.Results:We found that individuals with the L/L genotype showed higher scores on physical neglect (p=0.0047), anxiety symptoms (p=0.028), neuroticism (p=0.019) and perceived stress (p=0.035). L/L genotype was a risk factor for hazardous alcohol use in young adults (OR=3.06,p=0.0003). No GxE interactions were observed in our data.Conclusion:Our results provide novel evidence for the role of a functional polymorphism in theSLC6A4gene on the relationship of childhood trauma, anxiety-related traits and risky consumption of alcohol.

Risk and protective effects of serotonin and BDNF genes on stress-related adult psychiatric symptoms

We focused on individual risk by examining childhood adversity and current psychiatric symptoms in a sample of 100 college students genotyped for both the serotonin transporter (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF). Naturally occurring allelic variation in 5-HTTLPR (short/long) and BDNF (valine/methionine) have been strongly implicated in stress-related psychiatric risk, but the combined effects of these alleles on psychological functioning have yet to be fully elucidated. Univariate analysis revealed gene-environment correlations linking heightened psychiatric risk with past childhood adversity for short but not long 5-HTTLPR allelic carriers and for valine (Val) but not methionine (Met) BDNF allelic carriers. Multivariate analyses revealed a significant gene x gene interaction with results showing that risk varied systematically depending on both 5-HTTLPR and BDNF alleles, independent of childhood adversity. Hierarchical regression analyses indicated that approximately 11% of the variance in symptoms of depression could be specifically accounted for by the epistatic interaction of 5-HTTLPR and BDNF val66Met polymorphisms. Allelic group analyses indicated lowest risk, as measured by depression and anxiety, for allelic carriers of 5-HTTLPR-short and BDNF Met, followed by 5-HTTLPR-long and BDNF-Val, 5-HTTLPR-short and BDNF-Val, and 5-HTTLPR-long and BDNF-Met. Results suggest that protective or risk-enhancing effects on stress-related psychiatric functioning may depend on specific allelic combinations of 5-HTTLPR and BDNF.

Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study.

Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex. Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores. The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6). This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

Association between polymorphisms in the serotonin transporter gene-linked polymorphic region and risk for irritable bowel syndrome in China: evidence based on a meta-analysis.

ObjectiveThe association between mutations in the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and irritable bowel syndrome (IBS) differs between populations. This meta-analysis was designed to assess the relationship between 5-HTTLPR polymorphisms and IBS in a Chinese population.MethodsRelevant published studies from PubMed, Embase, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure databases were accessed prior to May 2018. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled using STATA software.ResultsA total of 754 IBS cases and 578 healthy controls in six studies were included in this meta-analysis. Significant results were obtained between 5-HTTLPR polymorphisms and IBS risk among studies with the genotype distribution of controls in Hardy–Weinberg equilibrium (L vs. S, OR = 1.41, 95% CI: 1.11–1.79; LL vs. SS, OR = 2.17, 95% CI: 1.16–4.08; LL vs. LS + SS, OR = 2.29, 95% CI: 1.25–4.20). In subgroup analyses, 5-HTTLPR polymorphisms were significantly associated with increased IBS-C risk in China; however, no risk was observed for IBS-D and IBS-M.ConclusionThis meta-analysis clearly indicates that 5-HTTLPR polymorphisms are associated with an increased risk of IBS in the Chinese population, especially IBS-C.

The 5-HTTLPR Polymorphism of the Serotonin Transporter Gene and the Intellectual Environment of Work Activity as Factors Associated with Changes to Memory in Aging

The heterogeneity of mental aging is due to the influences of both genetic and environmental factors. Among the latter, an important role is played by intellectual activity. An association was found between the serotonin transporter 5-HTTLPR gene and the efficiency of solving cognitive tasks, and the “adaptive” nature of one of its genotypes provided grounds for studying the associations of this polymorphism with age-related changes in cognitive functions in relation to the intellectual aspect of professional work. The study included young and old scientists (scientific activity, SA, N = 132) and people with no involvement in scientific activity (NSA, N = 157). The efficiency of verbal memory was assessed in terms of reproduction of words from the right and left ears in a dichotic test procedure and recognition of previously presented words; that of imaginal memory was assessed in terms of the recognition of figures. Independently of age, SA subjects had higher measures of verbal memory than NSA. The intellectual aspect of SA was a factor preventing age-related decline in memory for words addressed to the left hemisphere. Independently of other factors, carriers of the S′ (S or LG) alleles of the 5-HTTLPR polymorphism, as compared with carriers of the L′/L′ (LA/La) genotype, demonstrated better measures of imaginal memory. Thus, the initial cognitive potential and cognitive function-stimulating aspect of SA promotes maintenance of the functional activity of the left hemisphere. Measures of right-hemisphere imaginal memory were associated with the genome.

The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the sleep-promoting effects of tryptophan: A randomized placebo-controlled crossover study.

Background:The low-expressive short (S) allele of a functional polymorphism (5-HTTLPR) within the serotonin (5-hydroxytriptamine; 5-HT) transporter gene (SLC6A4) has been associated with a reduced functioning of the brain 5-HT system relative to the long (L) allele. As a consequence, the S-allele is found to predispose individuals to a higher risk of sleep quality reduction and clinical insomnia.Aims:The present study investigated whether subchronic pre-sleep tryptophan administration could compensate for this predisposition by improving sleep in 5-HTTLPR S-allele carriers.Methods:In a double-blind placebo-controlled crossover design a sample of homozygous 5-HTTLPR S-allele (n = 47) and L-allele (n = 51) carriers were assessed for subjective (sleep diary) and objective (actigraphy) sleep during a treatment protocol consisting of 1 week of placebo (1000 mg/day) and 1 week of tryptophan administration (1000 mg/day).Results:The results support the sleep-promoting effects of tryptophan. Tryptophan improved objective sleep efficiency and objective wake after sleep onset irrespective of allelic variation. There was a marginally significant improvement of subjective sleep quality in the 5-HTTLPR S-allele group but not in the L-allele group following tryptophan relative to placebo intake. In contrast, a significantly poorer sleep quality in the S-allele as opposed to the L-allele group in the placebo condition was not observed in the tryptophan condition.Conclusions:Tryptophan augmentation promises to be a valuable treatment strategy for sleep impairments related to genetic deficiencies in 5-HT functioning.

Cortisol awakening response and additive serotonergic genetic risk interactively predict depression in two samples: The 2019 Donald F. Klein Early Career Investigator Award Paper.

The serotonin system and hypothalamic pituitary-adrenal (HPA)-axis are each implicated in the pathway to depression; human and animal research support these systems' cross-talk. Our work implicates a 5-variant additive serotoninergic multilocus genetic profile score (MGPS) and separately the cortisol awakening response (CAR) in the prospective prediction of depression; other work has shown that the serotonin transporter polymorphism 5HTTLPR predicts CAR and interacts with the CAR to predict depression. We tested the hypothesis that a 6-variant MGPS (original plus 5HTTLPR) would interact with CAR to predict prospective depressive episode onsets in 201 emerging adults using four annual follow-up interviews. We also tested whether MGPS predicted CAR. We attempted replication of significant findings in a sample of 77 early adolescents predicting depression symptoms. In sample 1, MGPS did not significantly predict CAR. MGPS interacted with CAR to predict depressive episodes; CAR slopes for depression steepened as MGPS increased, for risk or protection. No single variant accounted for results, though CAR's interactions with 5HTTLPR and the original MGPS were both significant. In sample 2, the 6-variant MGPS significantly interacted with CAR to predict depression symptoms. Higher serotonergic MGPS appears to sensitize individuals to CAR level-for better and worse-in predicting depression.

The interplay of polygenic plasticity and adrenocortical activity as sources of variability in pathways among family adversity, youth emotional reactivity, and psychological problems.

This study examined the interplay between a polygenic composite and cortisol activity as moderators of the mediational pathway among family adversity, youth negative emotional reactivity to family conflict, and their psychological problems. The longitudinal design contained three annual measurement occasions with 279 adolescents (Mean age = 13.0 years) and their parents. Latent difference score analyses indicated that observational ratings of adversity in interparental and parent-child interactions at Wave 1 predicted increases in a multimethod, multi-informant assessment of youth negative emotional reactivity to family conflict from Waves 1 to 2. Changes in youth negative emotional reactivity, in turn, predicted increases in a multi-informant (i.e., parents, adolescent, and teacher) assessment of psychological problems from Waves 1 to 3. Consistent with differential susceptibility theory, the association between family adversity and negative emotional reactivity was stronger for adolescents who carried more sensitivity alleles in a polygenic composite consisting of 5-HTTLPR, DRD4 VNTR, and BDNF polymorphisms. Analyses of adolescent cortisol in the period surrounding a family disagreement task at Wave 1 revealed that overall cortisol output, rather than cortisol reactivity, served as an endophenotype of the polygenic composite. Overall cortisol output was specifically associated with polygenic plasticity and moderated the association between family adversity and youth negative emotional reactivity in the same for better or for worse manner as the genetic composite. Finally, moderator-mediated-moderation analyses indicated that the moderating role of the polygenic plasticity composite was mediated by the moderating role of adolescent cortisol output in the association between family adversity and their emotional reactivity.

SLC6A4 Repeat and Single-Nucleotide Polymorphisms Are Associated With Depression and Rest Tremor in Parkinson's Disease: An Exploratory Study.

Introduction: Level of serotonin is mainly regulated by the serotonin reuptake transporter encoded by SLC6A4. The promoter region of SLC6A4 bears a repeat polymorphism 5-HTTLPR and a single nucleotide polymorphism rs25531. We have previously studied the association between these two variants and sporadic PD. The objective of the current study was to determine whether the SLC6A4 polymorphisms were associated with key motor and non-motor symptoms of PD.Methods: A total of 370 PD patients of Han Chinese were included. Associations between the SLC6A4 polymorphisms and PD symptoms including depression, intellectual impairment, tremor and rigidity were analyzed.Results: 5-HTTLPR was associated with depression in PD patients and presence of the LL genotype was protective against the depression risk. The rs25531 was associated with rest tremor in PD and the A allele serves as a recessive risk allele. No associations were found in the two polymorphisms with respect to intellectual impairment and rigidity in the cohort.Conclusion: The current study reveals two PD symptoms associated with SLC6A4 polymorphisms, and provides new insight into how serotonergic system genetically participates in the symptomatic progression of PD. Further study is warranted in additional populations.

The Association between Serotonin Transporter Polymorphism, Platelet Serotonin Concentration and Insomnia in Non-Depressed Veterans with Posttraumatic Stress Disorder.

The role of serotonin transporter and its functional gene polymorphism (5-HTTLPR, serotonin transporter linked polymorphic region) was investigated in sleep disturbances in various mental disorders, with conflicting findings. Here, the association of particular sleep disturbances with 5-HTTLPR genotypes and platelet serotonin (5-HT) concentration was determined simultaneously in veterans with posttraumatic stress disorder (PTSD), who were subdivided into those with or without comorbid depression. Croatian male, medication-free war veterans with PTSD (N=325), subdivided into those with or without comorbid depression, and subdivided further according to the various sleep disturbances, were evaluated using the Structured Clinical Interview, the Hamilton Rating Scale for Depression and the Clinician Administered PTSD Scale. Genotyping and platelet 5-HT concentration measurements were conducted using PCR and spectrofluorimetric methods, respectively. Nominally higher frequency of the 5-HTTLPR LL genotype compared to S carriers (p=0.026; χ2 test) and significantly higher platelet 5-HT concentration (p=0.001; one-way ANOVA) were detected in non-depressed veterans with PTSD with early insomnia, compared to matched veterans without early insomnia. Over-representation of the LL genotype of the 5-HTTLPR and higher platelet 5-HT concentrations were detected in veterans with PTSD who did not develop comorbid depression but had severe early insomnia. These results suggest that 5-HTTLPR genotypes and platelet 5-HT concentration are associated with early insomnia in non-depressed veterans with PTSD. Limitations of the study were the cross-sectional nature of the study, biallelic assessment of the 5-HTTLPR, and a lack of use of the specific sleep measurement scales. These results should be replicated in larger samples, validated on different populations, using specific sleep measurement scales and triallelic 5-HTTLPR assessment.

Serotonin transporter gene methylation predicts long-term cortisol concentrations in hair

Epigenetic signatures, such as DNA methylation (DNAM), have been implicated in long-term dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis and related health risks. Based on a wealth of neuroendocrine studies on genetic polymorphisms in the serotonin transporter gene (SLC6A4), this locus constitutes a key candidate to explore associations of DNAM patterns and HPA-axis functioning. The few studies addressing this link so far exclusively relied on spot measurements of HPA-axis activity, which may not adequately reflect cortisol output over prolonged periods of time. To address this gap, hair cortisol concentrations (HCC), a valid measure of integrated long-term cortisol levels, were utilized to investigate endocrine correlates of SLC6A4 DNAM in 183 adults. Whole blood samples were drawn for DNAM analyses of 83 CpG sites within a 799-bp promoter-associated CpG island of SLC6A4 via bisulfite pyrosequencing. In addition, all participants were genotyped for the serotonin transporter polymorphism (5-HTTLPR). First, results revealed a significant negative association of SLC6A4 DNAM and HCC. Second, there was no significant main effect of 5-HTTLPR genotype on HCC when analyses were conducted on the basis of both bi-allelic classification and the 5-HTTLPR/rs25531 mini-haplotype. Third, the current data revealed a significant interaction of SLC6A4 DNAM and 5-HTTLPR genotype on HCC. Comparable to the pattern we had previously observed concerning cortisol stress reactivity, the S allele relates to increased HCC in individuals displaying low levels of SLC6A4 DNAM. By contrast, no such effect occurred under conditions of high SLC6A4 DNAM, indicating that epigenetic changes may compensate for genotype-dependent differences in long-term cortisol output. Together, respective findings support the idea of an epigenetic contribution to long-term HPA-axis activity and further highlight the usefulness of combining genetic and epigenetic information in future neuroendocrine studies.

Association Between 5-HTTLPR Polymorphism and the Risk of Autism: A Meta-Analysis Based on Case-Control Studies.

Background: Recently, many case-control studies have reported the association between 5-HTTLPR polymorphism and autism risk. However, the results are inconclusive and conflicting. To investigate the genetic association of 5-HTTLPR polymorphism and autism risk, we conducted a comprehensive meta-analysis based on previous case-control studies.Methods: Literature search was performed through PubMed, Embase, Web of Knowledge and CNKI databases until June 27, 2018. The strength of the association was assessed by relative risk (RR) and its corresponding 95% confidence interval (CI). Fixed or random effect model was selected based on the results of heterogeneity test. Further, subgroup analyses were conducted to explore the association of 5-HTTLPR polymorphism and autism risk in different population.Results: Eleven studies with 930 cases and 1234 controls were identified. Although there was a significant association between 5-HTTLPR polymorphism and autism risk under the dominant model after removing the studies causing heterogeneity, the significance did not exist after Bonferroni's correction. Subgroup analyses also showed similar results after Bonferroni's correction. In addition, there was no obvious publication bias in our meta-analysis.Conclusions: Our present meta-analysis does not support a direct effect of 5-HTTLPR polymorphism on autism risk according to present results. Further analyses of the effect of genetic networks and more well designed studies with larger sample size are required.

Effect of genetic polymorphism of brain-derived neurotrophic factor and serotonin transporter on smoking phenotypes: A pilot study of Japanese participants

PurposeThis study investigated whether a gene polymorphism causing a Val66Met substitution (rs6265) in brain-derived neurotrophic factor (BDNF) is associated with smoking initiation, smoking cessation, nicotine dependence and age of smoking initiation, in Japanese participants. Additionally, this study examined whether the S allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with the BDNF Val66Met polymorphism on smoking phenotypes. Patients and methodsThe genotypic proportion of the polymorphism responsible for BDNF Val66Met was determined in 148 participants including 88 current smokers, 21 former smokers, and 39 never smokers, and Fisher's exact test was used to investigate the relationship between this polymorphism and smoking cessation and initiation as well as the association between the genotypes of current smokers with a heavy smoking index (HSI) and the age of smoking initiation. In addition to the BDNF Val66Met polymorphism, the 5-HTTLPR polymorphism has also been evaluated in a specific subset of participants. ResultsWe found statistically significant correlations between the BDNF Val66Met polymorphism and the HSI, both in the whole study sample (P = 0.017) and in the male subgroup (P = 0.049). Moreover, the 5-HTTLPR polymorphism was associated with the age of smoking initiation in current smokers carrying the BDNF Met allele, in both the whole study sample (P = 0.041) and the male subgroup (P = 0.041). On the other hand, no association was observed between the BDNF Val66Met polymorphism, either alone or in combination with the 5-HTTLPR polymorphism, and the age of smoking cessation. Finally, no independent effects of the BDNF Val66Met genotype on the age of smoking initiation were detected. ConclusionThis pilot study provides preliminary findings regarding the influence of BDNF Val66Met on smoking phenotypes and the interacting effect of 5-HTTLPR on the association between BDNF Val66Met and smoking phenotypes in Japanese participants.

5-HTTLPR and COMT Val158Met are not associated with alexithymia: New evidence and meta-analyses

BackgroundsAlexithymia refers to the difficulties in identifying and describing one's own emotions, lacking of imagination, and an externally oriented thinking style. Studies up to date have examined the associations of 5-HTTLPR and COMT Val158Met polymorphisms with alexithymia. However, the previous findings were mixed. MethodsWe replicated the associations by scoring on alexithymia with the 20-item Toronto Alexithymia Scale and genotyping the polymorphisms of 5-HTTLPR and COMT Val158Met in a large population of college students (N = 1698). Moreover, we also meta-analyzed the associations with five samples (N = 7517) for the 5-HTTLPR and with five samples (N = 2186) for the COMT Val158Met. ResultsNeither the replicated study nor the meta-analyses indicated the 5-HTTLPR and COMT Val158Met were associated with alexithymia. ConclusionsThe findings suggest that the 5-HTTLPR and COMT Val158Met polymorphisms are not associated with alexithymia. However, genetic-environmental studies with different ethnicity and psychopathology should be carried in future.