Serotonin Transporter Gene Research Articles

Effects of stress on functional connectivity during verbal processing.

Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6 ± 1.6years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.

Effects of stress on functional connectivity during problem solving

AimOur purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect. MethodsForty-five healthy participants (Mean age: 19.6 ​± ​1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task. ResultsThere was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene ​× ​stress interaction on solution latency was also observed. DiscussionResults from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.

Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients.

Sexual dysfunction (SD) is a troublesome adverse effect of selective serotonin reuptake inhibitors (SSRIs). A variety of mechanisms might be involved in the occurrence of SD but the exact mechanism is still not clear. Genetic variations among patients treated with SSRIs are strong determinants of intolerance and poor compliance. The present study aimed to determine the relationship between serotonin-2A receptor (HTR2A) gene -1438A/G and 102T/C polymorphisms, serotonin transporter gene (SLC6A4) 5-HTT-linked polymorphic region (5-HTTLPR) insertion/deletion variant and brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphisms and the occurrence of SD adverse effect in major depressive disorder patients treated with citalopram (CIT) or sertraline (SERT). The result from this investigation revealed that the -1438A/G and 102T/C polymorphisms appear to be associated with the SD induced by CIT. It was also demonstrated that patients receiving SERT, carrying T allele of HTR2A or L allele of 5-HTTLPR more likely to experience SD. Most important overall finding of the study is the combined effects of -1438A/G, 102T/C, and 5-HTTLPR polymorphisms. In a logistic regression model, the occurrence of SD increased with the number of risky alleles. As compared with subjects receiving SERT with few risky (≤2) alleles, those with had 5-6 alleles had an increased SD risk. After all, according to these findings, -1438A/G, 102T/C, and 5-HTTLPR polymorphisms could be considered as promising pharmacogenetic biomarkers in CIT/SERT treatment in major depressive disorder (MDD) patients to avoid the occurrence of SD.

Differential Effects of Serotonin Transporter Genotype on Anxiety-Like Behavior and Cognitive Judgment Bias in Mice.

In humans, the short allele of a common polymorphism in the serotonin transporter (5-HTT) gene is associated with a higher risk to develop depression and anxiety disorders. Furthermore, individuals carrying this allele are characterized by negative judgment biases, as they tend to interpret ambiguous information in a more pessimistic way. 5-HTT knockout mice, lacking the 5-HTT gene either homo- or heterozygously, provide a widely used model organism for the study of symptoms related to human anxiety disorders. In the present study, we aimed to prove the anxiety-like phenotype of the 5-HTT mouse model, and to investigate whether 5-HTT genotype also causes differences in judgment bias. While our results confirm that homozygous 5-HTT knockout mice display highest levels of anxiety-like behavior, it was decreased in heterozygous mice. Against our expectations, we did not detect differences in the animals’ judgment bias. These results indicate that at least in mice the association between 5-HTT genotype and judgment bias is not straightforward and that other factors, including multiple genes as well as environmental influences, are implicated in the modulation of judgment biases. More research is needed to gain further insights into their function as potential endophenotypes for psychopathology.

Association of the DRD4 exon III and 5-HTTLPR VNTR polymorphisms with substance abuse in Jordanian Arab population

Genetic variations in the dopamine D4 receptor (DRD4) gene and the serotonin transporter (SLC6A4) gene are involved in the aetiology of substance abuse disorder (SUD). The main aim of this study is to evaluate the genetic association of DRD4 (48 bp-VNTR) and SLC6A4 (rs25531 and 5-HTTLPR VNTR) gene polymorphisms with SUD susceptibility among the Jordanian Arab population. This study included 500 SUD patients and 500 healthy matched controls. The VNTR Genetic polymorphisms of DRD4 and SLC6A4 genes were genotyped using conventional polymerase chain reaction (PCR). While, the rs25531 SNP was genotyped using PCR-restriction fragment length polymorphism (PCR-RFLP) technique. The genetic association was analysed using different statistical analyses including chi-square, Fisher exact test and one way ANOVA test. The DRD4 exon III VNTR polymorphism was associated with SUD significantly in case of alleles 4, 7 and genotype 7/7 (P = 0.004, 0.0005 and 0.01, respectively). While, there was no genetic association between the 5-HTTLPR (LL, LS, SS), rs25331 (AA, AG, GG) and tri-allelic (SASA, LASG, LASA, LALG, LALA) genotypes (P = 0.26, 0.71 and 0.52, respectively) and SUD. Moreover, using multinomial regression analysis, the homozygous 7/7 and 2/2 VNTR genotypes of DRD4 gene were nominally significantly associated with a lower risk of addiction (OR = 0.285 with P = 0.003 and OR = 0.447 with P = 0.031, respectively) after adjusting for other covariates. Our findings showed that 4 and 7 repeats and the genotype 7/7 of DRD4 exon III VNTRs polymorphism are involved in the aetiology of SUD among Jordanian population in compared to the 5-HTTLPR polymorphisms.

P.332 Deconstructing major depressive episodes by severity and chronicity: A cross-diagnostic cluster-analysis on a large, international, observational study

Current diagnostic classifications regard psychotic symptoms during depressive episodes as indicators of depression severity. However, growing evidence suggests that depression with psychotic symptoms (MDP) may represent a distinct subtype of depression. In the course of the search for discriminating factors we tested the hypothesis that the serotonin transporter gene (5-HTTLPR) may interact with the manifestation of psychotic symptoms in acute depression.112 inpatients (61 female) with a depressive episode (16 bipolar, 86 unipolar) at admission were genotyped for 5-HTTLPR variants. Psychotic symptoms und general psychopathology were evaluated comprehensively using the Manual of the Association for Methodology and Documentation in Psychiatry (Arbeitsgemeinschaft für Methodik und Dokumentation in der Psychiatrie, 1981). For statistical analysis a chi-square test and a logistic regression model was used.16 (14.3%) out of 112 patients were currently presenting with psychotic symptoms. The primary finding of our study was the higher prevalence of the s-allele of the 5-HTTLPR within the group of MDP patients (Pearson χ²=7.87; df=2; p<0.03). Secondly, in a logistic regression model, 5-HTTLPR was found to significantly contribute to the diagnosis of MDP (χ²=6.5; df=1; p=0.01). This effect was even more pronounced upon comparing only severely depressed patients with MDP patients. From a psychopathological perspective, MDP patients showed higher AMDP hostility and apathy scores but equal AMDP depression scores.This is the first study to show an influence of 5-HTTLPR on psychotic symptoms in acutely depressed patients.The lack of a control group and the relatively small sample size limits the present study's findings, thus replication in a larger sample is necessary.

Pain-related increase in serotonin transporter gene methylation associates with emotional regulation in 4.5-year-old preterm-born children.

The main goal of this study was to assess the association between pain-related increase in serotonin transporter gene (SLC6A4) methylation and emotional dysregulation in 4.5-year-old preterm children compared with full-term matched counterparts. Preterm (n=29) and full-term (n=26) children recruited from two Italian hospitals were followed-up from October 2011 to December 2017. SLC6A4 methylation was assessed from cord blood at birth from both groups and peripheral blood at discharge for preterm ones. At 4.5years, emotional regulation (ie, anger, fear and sadness) was assessed through an observational standardised procedure. Preterm children (18 females; mean age=4.5, range=4.3-4.8) showed greater anger display compared with full-term controls (14 females; mean age=4.5, range=4.4-4.9) in response to emotional stress. Controlling for adverse life events occurrence from discharge to 4.5years and SLC6A4 methylation at birth, CpG-specific SLC6A4 methylation in the neonatal period was predictive of greater anger display in preterm children but not in full-term ones. These findings contribute to highlight how epigenetic regulation of serotonin transporter gene in response to NICU pain exposure contributes to long-lasting programming of anger regulation in preterm children.

Mouse model of the human serotonin transporter-linked polymorphic region

Genetic factors play a significant role in risk for mood and anxiety disorders. Polymorphisms in genes that regulate the brain monoamine systems, such as catabolic enzymes and transporters, are attractive candidates for being risk factors for emotional disorders given the weight of evidence implicating monoamines involvement in these conditions. Several common genetic variants have been identified in the human serotonin transporter (5-HTT) gene, including a repetitive sequence located in the promoter region of the locus called the serotonin transporter-linked polymorphic region (5-HTT-LPR). This polymorphism has been associated with a number of mental traits in both humans and primates, including depression, neuroticism, and harm avoidance. Some, but not all, studies found a link between the polymorphism and 5-HTT levels, leaving open the question of whether the polymorphism affects risk for mental traits via changes in 5-HTT expression. To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioral traits, we set out to develop a mouse model of the human 5-HTT-LPR. Here we describe the creation and characterization of a set of mouse lines with single-copy human transgenes carrying the short and long 5-HTT-LPR variants. Although we were not able to detect differences in expression between the short and long variants, we encountered several technical issues concerning the design of our humanized mice that are likely to have influenced our findings. Our study serves as a cautionary note for future studies aimed at studying human transgene regulation in the context of the living mouse.

Biological Aspects of Aggression and Violence in Schizophrenia.

Although the majority of patients with schizophrenia are not actually violent, an increased tendency toward violent behaviors is known to be associated with schizophrenia. There are several factors to consider when identifying the subgroup of patients with schizophrenia who may commit violent or aggressive acts. Comorbidity with substance abuse is the most important clinical indicator of increased aggressive behaviors and crime rates in patients with schizophrenia. Genetic studies have proposed that polymorphisms in the promoter region of the serotonin transporter gene and in the catechol-O-methyltransferase gene are related to aggression. Neuroimaging studies have suggested that fronto-limbic dysfunction may be related to aggression or violence. By identifying specific risk factors, a more efficient treatment plan to prevent violent behavior in schizophrenia will be possible. Management of comorbid substance use disorder may help prevent violent events and overall aggression. Currently, clozapine may be the only effective antipsychotic medication to repress aggressive behavior. With the current medical field moving toward tailored medicine, it is important to identify vulnerable schizophrenia populations and provide efficient treatment.

Therapeutic implications of the serotonin transporter gene in depression

Abstract Background A natural variant of the serotonin transporter gene has been studied in mood disorders and its treatment with serotonin transporter inhibitors. It is now available on gene testing profiles to help guide treatment. But the actual interpretation of the data regarding clinical actionable items is controversial. Methods A review is undertaken to understand the role of the short form in the biology of the brain and its effect on depression and response to serotoninergic antidepressants. Results There are naturally occurring variants of the serotonin reuptake transporter (SERT) gene that express approximately 50 % fewer SERT units in the synapse. People with these low-expressing variants (frequently referred to as the ‘short form’) are more likely to: 1) develop depression in the setting of adversity; 2) attempt or re-attempt suicide; 3) respond inadequately to an antidepressant; 4) develop side effects when taking an antidepressant; or 5) develop rapid cycling if they have bipolar illness. Emerging data suggest that due to the similarity between these natural variants and the mechanism of action of most antidepressants, chronic use of antidepressants may significantly worsen these consequences in patients with the low-expressing variants or induce similar outcomes in people that do not have the short form variants. Conclusions Greater caution is required regarding exposure to serotonin reuptake inhibitors (or serotonin/norepinephrine reuptake inhibitors) for people that have the low expressing short form variants of SERT.

Impact of Polymorphisms in the Serotonin Transporter Gene on Oscillatory Dynamics during Inhibition of Planned Movement in Children.

The serotonin transporter plays an important role in serotonergic neuromodulation. It is known that polymorphisms in the serotonin transporter gene are linked to the dysregulation of emotions. In the current study, we aimed to investigate the impact of variation in the gene encoding serotonin transporter polymorphism on oscillatory dynamics during inhibition of planned movement in the stop signal paradigm. During performance the stop signal paradigm, electroencephalograms (EEGs) were recorded in 90 healthy Caucasian children (39 girls) from 7 to 12 years. Buccal epithelium probes were taken from all participants. The La, Lg, and S alleles of serotonin transporter-linked polymorphic region (5-HTTLPR) polymorphism were detected in the DNA samples using PCR. LaLa genotype carriers did not differ from LaS\\LgS and LgS\\LgLg\\SS carriers in a number of successful inhibitions of a prepotent response. Carriers of LaLa exhibit higher alpha and beta event-related spectral perturbations (ERSP) in parietal and occipital cortices after the presentation of signal of inhibition of movement than LaS\\LgS and LgS\\LgLg\\SS carriers. Results are consistent with current literature and confirm that S allele carriers are more predisposed to disturbances in cognitive control.

Rare variants in SLC6A4 cause susceptibility to major depressive disorder with suicidal ideation in Han Chinese adolescents and young adults

BackgroundSuicidal ideation (SI) is the most serious symptom of major depressive disorder (MDD) and considered an extreme state. The serotonin transporter gene (SLC6A4) plays a significant role in MDD and suicide pathophysiology. Previous studies have revealed an association between common variants of SLC6A4 with the risk of MDD and suicide. However, very few studies have so far focused on the degree to which rare variants of SLC6A4 are responsible for the depression observed in adolescent and young adult suicide patients. The aim of this study was to examine the impact of common and rare variants of SLC6A4 on the risk of Han Chinese adolescents and young adults suffering MDD with SI. MethodsTargeted sequencing of the SLC6A4 gene was conducted using FastTarget technology in Han Chinese adolescents and young adults, of which 74 were MDD patients with SI and 150 were healthy controls. Gene-based association analyses of rare variants were performed using enrichment analysis and a cumulative allele test. An allele association study was performed against common variants. ResultsAfter sequencing and bioinformatics analysis, a total of 15 single nucleotide variants (SNVs) were detected in the targeted regions from all participants, including 9 common and 6 rare variants. Among these, 5 rare variants were identified within the study group. Enrichment analysis of rare variants demonstrated a statistical difference (p = 0.042) between the study and control groups. Using cumulative allele analysis, alternative alleles in the SLC6A4 gene exhibited an association with MDD patients with SI (cumulative allele: OR = 10.18, 95% CI = 1.18–87.32, p = 0.017). No significant association was found between the 9 common SLC6A4 variants and MDD patients with SI. ConclusionsOur results suggest that rare variants of SLC6A4 may contribute to a genetic risk of adolescents and young adults suffering MDD with SI.

Genetics of resilience: Implications from genome-wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression.

Resilience is the ability to cope with critical situations through the use of personal and socially mediated resources. Since a lack of resilience increases the risk of developing stress-related psychiatric disorders such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), a better understanding of the biological background is of great value to provide better prevention and treatment options. Resilience is undeniably influenced by genetic factors, but very little is known about the exact underlying mechanisms. A recently published genome-wide association study (GWAS) on resilience has identified three new susceptibility loci, DCLK2, KLHL36, and SLC15A5. Further interesting results can be found in association analyses of gene variants of the stress response system, which is closely related to resilience, and PTSD and MDD. Several promising genes, such as the COMT (catechol-O-methyltransferase) gene, the serotonin transporter gene (SLC6A4), and neuropeptide Y (NPY) suggest gene × environment interaction between genetic variants, childhood adversity, and the occurrence of PTSD and MDD, indicating an impact of these genes on resilience. GWAS on PTSD and MDD provide another approach to identifying new disease-associated loci and, although the functional significance for disease development for most of these risk genes is still unknown, they are potential candidates due to the overlap of stress-related psychiatric disorders and resilience. In the future, it will be important for genetic studies to focus more on resilience than on pathological phenotypes, to develop reasonable concepts for measuring resilience, and to establish international cooperations to generate sufficiently large samples.

No evidence for the involvement of serotonin or the 5-HTTLPR genotype in intertemporal choice in a larger community sample.

Serotonin has been implicated in impulsive behaviours such as temporal discounting. While animal studies and theoretical approaches suggest that reduced tonic serotonin levels increase temporal discounting rates and vice versa, evidence from human studies is scarce and inconclusive. Furthermore, an important modulator of serotonin signalling, a genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR), has not been investigated for temporal discounting so far. First, the purpose of this study was to test for a significant association between 5-HTTLPR and temporal discounting. Second, we wished to investigate the effect of high/low tonic serotonin levels on intertemporal choice and blood oxygen-level-dependent response, controlling for 5-HTTLPR. We tested the association of 5-HTTLPR with temporal discounting rates using an intertemporal choice task in 611 individuals. We then manipulated tonic serotonin levels with acute tryptophan interventions (depletion, loading, balanced) in a subsample of 45 short (S)-allele and 45 long (L)/L-allele carriers in a randomised double-blind crossover design using functional magnetic resonance imaging and an intertemporal choice task. Overall, we did not find any effect of serotonin and 5-HTTLPR on temporal discounting rates or the brain networks associated with valuation and cognitive control. Our findings indicate that serotonin may not be directly involved in choices including delays on longer timescales such as days, weeks or months. We speculate that serotonin plays a stronger role in dynamic intertemporal choice tasks where the delays are on a timescale of seconds and hence are therefore directly experienced during the experiment.

The Psilocybin-Telomere Hypothesis: An empirically falsifiable prediction concerning the beneficial neuropsychopharmacological effects of psilocybin on genetic aging

We introduce a novel hypothesis which states that the therapeutic utilisation of psilocybin has beneficial effects on genetic aging. Ex hypothesi, we predict a priori that controlled psilocybin interventions exert quantifiable positive impact on leucocyte telomere length (telomeres are a robust predictor of mortality and multifarious aging-related diseases). Our hypothesising follows the Popperian logic of scientific discovery, viz., bold (and refutable) conjectures form the very foundation of scientific progress. The ‘psilocybin-telomere hypothesis‘ is formalised as a logically valid deductive (syllogistic) argument and we provide substantial evidence to support the underlying premises. Impetus for our theorising derives from a plurality of converging empirical sources indicating that psilocybin has persistent beneficial effects on various aspects of mental health (e.g., in the context of depression, anxiety, PTSD, OCD, addiction, etc.). Additional support is based on a large corpus of studies that establish reliable correlations between mental health and telomere attrition (improved mental health is generally correlated with longer telomeres). Another pertinent component of our argument is based on recent studies which demonstrate that “meditative states of consciousness” provide beneficial effects on genetic aging. Similarly, psilocybin can induce states of consciousness that are neurophysiologically and phenomenologically significantly congruent with meditative states. Furthermore, prior research has demonstrated that a single dose of psilocybin can occasion life-changing transformative experiences (≈ 70% of healthy volunteers rate their experience with psilocybin amongst the five personally most meaningful lifetime events, viz., ranked next to giving birth to a child or losing a loved one). We postulate that these profound psychological events leave quantifiable marks at the molecular genetic/epigenetic level. Given the ubiquitous availability and cost effectiveness of telomere length assays, we suggest that quantitative telomere analysis should be regularly included in future psilocybin studies as an adjunctive biological marker (i.e., to facilitate scientific consilience via methodological triangulation). In order to substantiate the ‘psilocybin-telomere hypothesis’ potential neuropsychopharmacological, endocrinological, and genetic mechanisms of action are discussed (e.g., HPA-axis reactivity, hippocampal neurogenesis, neurotropic growth factors such as BDNF, 5-HT2A receptor agonism, neuroplasticity/synaptoplasticity, brain-wide alterations in neuronal functional connectivity density, involvement of the SLC6A4 serotonin transporter gene, inter alia). The proposed research agenda is thus intrinsically highly interdisciplinary, and it has deep ramifications from a philosophy of science perspective as it connects the epistemic level (qualitative experiential phenomenology) with the ontic level (quantitative molecular genetics) of analysis. In the long term, multidisciplinary and innovative investigations of the ‘psilocybin-telomere hypothesis‘ could contribute to the improvement of senotherapeutic psychological interventions and the identification of novel geroprotective and neuroprotective/restorative pharmaceutical targets to decelerate genetic aging and improve well-being and quality of life during the aging process.

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.

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.

Shared Reading at Age 1 Year and Later Vocabulary: A Gene–Environment Study

To assess the extent to which associations between shared reading at age 1 years and child vocabulary at age 3 years differ based on the presence of sensitizing alleles in the dopaminergic and serotonergic neurotransmitter systems. We conducted a secondary analysis of data from a national urban birth cohort using mother reports in conjunction with child assessments and salivary genetic data. Child vocabulary was assessed using the Peabody Picture Vocabulary Test. The primary exposure was mother-reported shared reading. We used data on gene variants that may affect the function of the dopaminergic and serotonergic systems. We examined associations between shared reading and Peabody Picture Vocabulary Test score using multiple linear regression. We then included interaction terms between shared reading and the presence of sensitizing alleles for each polymorphism to assess potential moderator effects adjusting for multiple comparisons. Of the 1772 children included (56% black, 52% male), 31% of their mothers reported reading with their child daily. Daily shared reading was strongly associated with child Peabody Picture Vocabulary Test scores in unadjusted (B=7.9; 95% CI, 4.3-11.4) and adjusted models (B=5.3; 95% CI, 2.0-8.6). The association differed based on the presence of sensitizing alleles in the dopamine receptor 2 and serotonin transporter genes. Among urban children, shared reading at age 1 years was associated with greater vocabulary at age 3 years. Although children with sensitizing alleles on the dopamine receptor 2 and serotonin transporter genes were at greater risk when not read to, they fared as well as children without these alleles when shared reading occurred.

Serotonin Transporter (5-HTT) Gene Polymorphisms and Susceptibility to Chronic Periodontitis: A Case-Control Study.

Objective: The current study is aimed at exploring the relationship between chronic periodontitis and serotonin transporter (5-HTT) gene polymorphisms (rs6354 and rs12449783) in the Chinese Han population. Methods: This study included a total of 120 patients with chronic periodontitis and 125 healthy control subjects. The 5-HTT gene (rs6354 and rs12449783) was genotyped using oral mucosal tissue with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Linkage disequilibrium was examined using Haploview. Genotype and allele frequencies were compared between the cases and controls using a χ2 test. Results: Genotype distribution of the 5-HTT gene polymorphisms rs6354 and rs12449783 in the control group conformed to Hardy–Weinberg equilibrium. The frequency of the AC genotype, the AC + CC genotype and C allele of the 5-HTT rs6354 polymorphism was higher in cases (P < 0.05) vs. the healthy control. The adjusted odds ratio (OR) was 1.910 (95%CI = 1.049–3.476) for the AC genotype, 2.026 (95%CI = 1.115–3.680) for the AC+CC genotype, and 1.875 for the C allele (95%CI = 1.089–3.228. Such an association was particularly strong in women for the AC genotype (OR = 2.167, 95%CI = 1.034–4.542). The genotype and allele frequencies of rs12449783 did not differ between the cases and controls. Haplotype C-C (rs6354-rs12449783) was also more frequent in the cases (OR = 2.372, 95%CI = 1.154–4.875, P = 0.016). Conclusion: Chronic periodontitis is associated with the 5-HTT gene rs6354 polymorphism, as well as rs6354/rs12449783 interaction.

An Investigation of Genetic Polymorphism In The Rs35521 Serotonin Transporter Gene In Allergic Rhinitis

Objective: Allergic rhinitis (AR) is one of the most frequently encountered allergic disorders and has a typical prevalence of between 18 and 40%.The factors which underlie allergic disorders may vary since they are linked to climate, geography, different social conditions and genetic makeup. The objective of our research was to investigate any connections between polymorphism in the serotonin transporter gene and allergic rhinitis. Methods: This study involved the participation of two groups aged between 15 and 60 years of age who attended the ENT clinic of the Medical Faculty at Erzincan University: 100 individuals with allergic rhinitis plus a control group of 200 individuals who lacked the condition. The AR cases were established on the basis of history, physical examination and skin prick testing. Peripheral blood samples were taken from both groups and subjected to genetic analyses. The analysis utilised a 5-HTT Taqman® primer as genetic probe. The Chi-squared method was utilised for statistical analysis. Results: 129 of the participants were female (64.5%) and 71 (35.5%) male. The average age of those participating was 34.5 ± 14.6 (range: 20-65) years. In reference to the sex distribution of the patients, 79% of the patients were female. There was a significant difference between the groups according to sex (p <0.01). No significant differences were noted between the patient and control groups when compared according to genetic polymorphism or place of residence. In 61% of the allergic rhinitis sufferers, their symptoms were seasonal. The incidence of AR was higher in both females and in those living in an urban rather than rural setting. When the polymorphism is examined in both the patient and control groups, the most common type is the mutant type. In both the cases and controls, when the polymorphism was investigated, the most frequently seen type was the Mutant variety and no significant difference in frequency was noted according to sex or place of residence. Conclusion: In this study, when the cases and controls were compared in terms of the polymorphism in the rs35521 serotonin transporter gene, there was no difference at the level of statistical significance between the frequency of occurrence of the mutant or heterozygote form of the gene.