Serotonin Transporter Gene Polymorphism Research Articles

Association between serotonin transporter gene polymorphisms and heroin dependence: a meta-analytic study.

BackgroundStudies have examined the association between heroin dependence and serotonin transporter gene polymorphisms but yielded inconsistent results. The purpose of current study is to determine the overall effect of these polymorphisms on the risk for heroin dependence through a meta-analytic method.MethodsA meta-analysis was conducted to examine the association of heroin dependence with two common polymorphisms of serotonin transporter gene, in the promoter (5-hydroxytryptamine transporter-linked promotor region [5-httlpr]) and intron 2 (a various number tandem repeat in serotonin transporter intron 2 [STin2]). Data from studies with 5-httlpr (6 studies) and STin2 (8 studies) were synthesized by random effects model.ResultsIn the analysis, heroin dependence was found to be significantly associated with the S allele of 5-httlpr (odds ratio [OR] =1.22, 95% confidence interval [CI] =1.08–1.41, P=0.002). The association between the S allele of 5-httlpr and heroin dependence was significant in Caucasian subjects (OR =1.37, 95% CI =1.12–1.68, P=0.003), but not in non-Caucasian subjects. On the other hand, no association with STin2 polymorphism was found (OR =1.14, 95% CI =0.91–1.42, P=0.242).ConclusionThe results suggest an ethnic-specific effect of the 5-httlpr polymorphism on the risk for heroin dependence, but the influence of the genetic variance in the patients with comorbidities or intermediate phenotypes of heroin dependence needs to be further examined.

Association of STin2 VNTR Polymorphism of Serotonin Transporter Gene with Lifelong Premature Ejaculation: A Case-Control Study in Han Chinese Subjects.

BackgroundThe STin2 VNTR polymorphism has a variable number of tandem repeats in intron 2 of the serotonin transporter gene. We aimed to explore the relationship between STin2 VNTR polymorphism and lifelong premature ejaculation (LPE).Material/MethodsWe recruited a total of 115 outpatients who complained of ejaculating prematurely and who were diagnosed as LPE, and 101 controls without PE complaint. Allelic variations of STin2 VNTR were genotyped using PCR-based technology. We evaluated the associations between STin2 VNTR allelic and genotypic frequencies and LPE, as well as the intravaginal ejaculation latency time (IELT) of different STin2 VNTR genotypes among LPE patients.ResultsThe patients and controls did not differ significantly in terms of any characteristic except age. A significantly higher frequency of STin2.12/12 genotype was found among LPE patients versus controls (P=0.026). Frequency of patients carrying at least 1 copy of the 10-repeat allele was significantly lower compared to the control group (28.3% vs. 41.8%, OR=0.55; 95%CI=0.31–0.97, P=0.040). In the LPE group, the mean IELT showed significant difference in STin2.12/12 genotype when compared to those with STin2.12/10 and STin2.10/10 genotypes. The mean IELT in10-repeat allele carriers was 50% longer compared to homozygous carriers of the STin2.12 allele.ConclusionsOur results indicate the presence of STin2.10 allele is a protective factor for LPE. Men carrying the higher expression genotype STin2. 12/12 have shorter IELT than 10-repeat allele carriers.

Implicit association to infant faces: Genetics, early care experiences, and cultural factors influence caregiving propensities

Genetics, early experience, and culture shape caregiving, but it is still not clear how genetics, early experiences, and cultural factors might interact to influence specific caregiving propensities, such as adult responsiveness to infant cues. To address this gap, 80 Italian adults (50% M; 18–25 years) were (1) genotyped for two oxytocin receptor gene polymorphisms (rs53576 and rs2254298) and the serotonin transporter gene polymorphism (5-HTTLPR), which are implicated in parenting behaviour, (2) completed the Adult Parental Acceptance/Rejection Questionnaire to evaluate their recollections of parental behaviours toward them in childhood, and (3) were administered a Single Category Implicit Association Test to evaluate their implicit responses to faces of Italian infants, Japanese infants, and Italian adults. Analysis of implicit associations revealed that Italian infant faces were evaluated as most positive; participants in the rs53576 GG group had the most positive implicit associations to Italian infant faces; the serotonin polymorphism moderated the effect of early care experiences on adults’ implicit association to both Italian infant and adult female faces. Finally, 5-HTTLPR S carriers showed less positive implicit responses to Japanese infant faces. We conclude that adult in-group preference extends to in-group infant faces and that implicit responses to social cues are influenced by interactions of genetics, early care experiences, and cultural factors. These findings have implications for understanding processes that regulate adult caregiving.

Does preoperative depression and/or serotonin transporter gene polymorphism predict outcome after laparoscopic cholecystectomy?

ObjectiveTo determine whether preoperative psychological depression and/or serotonin transporter gene polymorphism are associated with poor outcomes after the common procedure of laparoscopic cholecystectomy.DesignPatients undergoing laparoscopic cholecystectomy were genotyped for the serotonin transporter gene 5-HTTLPR polymorphism and assessed for psychological morbidity before and 6 weeks after surgery. The main outcome was postoperative depression; secondary outcomes included fatigue, perceived pain, quality of life and subjective perception about return to usual.ResultsFull genetic and psychological data were obtained from 273 out of 330 patients consented to the study (82% female). Significantly fewer people with preoperative depression (Beck Depression Inventory (BDI) score >5) had returned to employment (57% vs 86%, p<0.001) or made a full recovery (11% vs 44%, p<0.001) 6 weeks after surgery. Independent predictors for subjective return to usual after surgery included preoperative depression, body mass index and postoperative pain scores. Independent predictors of postoperative depression included preoperative antidepressant use and preoperative depression. SS genotype was associated with use of antidepressants preoperatively and higher anxiety levels after surgery. However, it was not associated with other salient postoperative psychosocial outcomes.ConclusionsDepressive psychological morbidity preoperatively, pain and body mass index appear to be important factors in predicting recovery after this common surgical procedure. There may be a place to include preoperative brief psychological screening to enable targeted support. Our results suggest that the serotonin transporter gene is unlikely to be a useful clinical predictor of outcome in this group.Trial registration numberISRCTN40219584.

Interplay between stress response genes associated with attention-deficit hyperactivity disorder and brain volume.

The glucocorticoid receptor plays a pivotal role in the brain's response to stress; a haplotype of functional polymorphisms in the NR3C1 gene encoding this receptor has been associated with attention-deficit hyperactivity disorder (ADHD). The serotonin transporter (5-HTT) gene polymorphism 5-HTTLPR is known to influence the relation between stress exposure and ADHD severity, which may be partly because of its reported effects on glucocorticoid levels. We therefore investigated if NR3C1 moderates the relation of stress exposure with ADHD severity and brain structure, and the potential role of 5-HTTLPR. Neuroimaging, genetic and stress exposure questionnaire data were available for 539 adolescents and young adults participating in the multicenter ADHD cohort study NeuroIMAGE (average age: 17.2 years). We estimated the effects of genetic variation in NR3C1 and 5-HTT, stress exposure and their interactions on ADHD symptom count and gray matter volume. We found that individuals carrying the ADHD risk haplotype of NR3C1 showed significantly more positive relation between stress exposure and ADHD severity than non-carriers. This gene-environment interaction was significantly stronger for 5-HTTLPR L-allele homozygotes than for S-allele carriers. These two- and three-way interactions were reflected in the gray matter volume of the cerebellum, parahippocampal gyrus, intracalcarine cortex and angular gyrus. Our findings illustrate how genetic variation in the stress response pathway may influence the effects of stress exposure on ADHD severity and brain structure. The reported interplay between NR3C1 and 5-HTT may further explain some of the heterogeneity between studies regarding the role of these genes and hypothalamic-pituitary-adrenal axis activity in ADHD.

Serotonin transporter gene (SLC6A4) polymorphisms are associated with response to fluoxetine in south Indian major depressive disorder patients

Up to 30-40% of the major depressive disorder patients do not respond sufficiently to antidepressant treatment. Genetic variations in the serotonin transporter gene have been implicated in modulating treatment response to selective serotonin reuptake inhibitors, and this association is influenced by ethnicity. We investigated the influence of serotonin transporter gene variants 5-HTTLPR and rs25531 in Indian population on fluoxetine response. One hundred and two major depressive disorder patients were started on fluoxetine treatment and after 6weeks, classified as responders (n=56) and non-responders (n=46) using Hamilton depression rating scale and genotyped. Fisher's exact test was used to compare genotype frequencies between responders and non-responders. One-way analysis of variance and student t test were used to compare the percentage reduction (week 0-6) in Hamilton depression rating scores between genotype and haplotype groups. We observed a significant association between LL genotype of 5-HTTLPR and fluoxetine treatment response (p=0.0066, OR (95%)=4.0 (1.45-11.03)) but not with the functional groups of 5-HTTLPR -rs25531. However, there was a significant difference in percentage reduction in HAM-D scores (week 0-6) between 5-HTTLPR genotypes (LL vs. LS+SS, p=0.0036; LL vs. LS, p=0.0109) as well as the functionally grouped haplotypes of 5-HTTLPR -rs25531 (LALA carriers vs. non-carriers of LALA, p=0.0118; LALA vs. LAS+ LALG, p=0.0419). The LL genotype and LALA haplotype of SLC6A4 are associated with favorable treatment response to fluoxetine in south Indian major depression patients.

The First 5-Year-Long Survey on Intrauterine Unexplained Sudden Deaths from the Northeast Italy

ABSTRACTPurpose: Sudden intrauterine unexplained death syndrome (SIUDS) represents one of the main open issues in the scientific and social setting of the modern medicine, and our efforts have aimed to understand its possible causes and risk factors. Methods: A 43-case series of consecutive unexplained fetal deaths coming from Northeast Italy, collected in a 5-year period (2011–2015), has been submitted to an in-depth investigation, based on neuropathological and cardiopathological examinations, immunohistochemistry for neuronal nuclear antigen (NeuN), genetic characterization for the serotonin transporter (5-HTT) gene polymorphisms, and toxicological environmental analyses. Results: The overall survey from the neuropathological findings highlights one or more congenital morphological abnormalities of the autonomic nervous system in 77% of cases of sudden fetal deaths. Conclusions: From our results emerges the need to perform a complete autopsy of all SIUDS victims with an in-depth examination of the neuronal centers of the brainstem, which modulate the vital functions.

Predictors for self-directed aggression in Italian prisoners include externalizing behaviors, childhood trauma and the serotonin transporter gene polymorphism 5-HTTLPR.

Suicidal behavior and self-mutilation can be regarded as the expression of self-directed aggression and both are common in prison populations. We investigated the influence of externalizing behaviors, depressive symptoms, childhood trauma, 5-HTTLPR variants on self-directed aggression (N = 145) in a group of 702 male Italian prisoners. Participants were comprehensively evaluated, including for psychiatric disorders, impulsive traits, lifetime aggressive behavior [Brown-Goodwin Lifetime History of Aggression (BGHA)], hostility, violent behavior during incarceration, depressive symptomatology [Hamilton Depression Rating Scale (HDRS)], childhood trauma [Childhood Trauma Questionnaire (CTQ)]. Logistic regression analysis showed false discovery rate corrected independent main effects of externalizing behaviors: BGHA (P = 0.001), violent behavior in jail (P = 0.007), extraversion (P = 0.015); HDRS (P = 0.0004), Axis I disorders (P = 0.015), CTQ (P = 0.004) and 5-HTTLPR genotype (P = 0.02). Carriers of 5-HTTLPR high (LA LA ), intermediate (LA LG , SLA ) activity variants were more likely to have exhibited self-directed aggression relative to the low activity (LG LG , SLG , SS) variant: high/low: odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.27-4.68, P = 0.007; intermediate/low: OR = 1.96, 95% CI 1.09-3.68, P = 0.025. The CTQ main effect was driven by physical abuse. There was no interactive effect of 5-HTTLPR and CTQ. Secondary logistic regression analyses in (1) all suicide attempters (N = 88) and (2) all self-mutilators (N = 104), compared with controls showed that in both groups, childhood trauma (P = 0.008-0.01), depression (P = 0.0004-0.001) were strong predictors. BGHA, violent behavior in jail predicted self-mutilation (P = 0.002) but not suicide attempts (P = 0.1). This study was able to distinguish differing influences on self-directed aggression between groups of closely related predictor variables within the externalizing behavioral domain. 5-HTTLPR had an independent, variant dosage effect.

Meta-analysis of the serotonin transporter promoter variant (5-HTTLPR) in relation to adverse environment and antisocial behavior.

Several studies have suggested an association between antisocial, aggressive, and delinquent behavior and the short variant of the serotonin transporter gene polymorphism (5-HTTLPR). Yet, genome wide and candidate gene studies in humans have not convincingly shown an association between these behaviors and 5-HTTLPR. Moreover, individual studies examining the effect of 5-HTTLPR in the presence or absence of adverse environmental factors revealed inconsistent results. We therefore performed a meta-analysis to test for the robustness of the potential interaction effect of the "long-short" variant of the 5-HTTLPR genotype and environmental adversities, on antisocial behavior. Eight studies, comprising of 12 reasonably independent samples, totaling 7,680 subjects with an effective sample size of 6,724, were included in the meta-analysis. Although our extensive meta-analysis resulted in a significant interaction effect between the 5-HTTLPR genotype and environmental adversities on antisocial behavior, the methodological constraints of the included studies hampered a confident interpretation of our results, and firm conclusions regarding the direction of effect. Future studies that aim to examine biosocial mechanisms that influence the etiology of antisocial behavior should make use of larger samples, extend to genome-wide genetic risk scores and properly control for covariate interaction terms, ensuring valid and well-powered research designs. © 2016 Wiley Periodicals, Inc.

Association between serotonin transporter gene polymorphism and recurrent aphthous stomatitis

Anxiety-related traits have been attributed to sequence variability in the genes coding for serotonin transmission in the brain. Two alleles, termed long (L) and short (S) differing by 44 base pairs, are found in a polymorphism identified in the promoter region of serotonin transporter gene. The presence of the short allele and SS and LS genotypes is found to be associated with the reduced expression of this gene decreasing the uptake of serotonin in the brain leading to various anxiety-related traits. Recurrent aphthous stomatitis (RAS) is an oral mucosal disease with varied etiology including the presence of stress, anxiety, and genetic influences. The present study aimed to determine this serotonin transporter gene polymorphism in patients with RAS and compare it with normal individuals. This study included 20 subjects with various forms of RAS and 20 normal healthy age- and gender-matched individuals. Desquamated oral mucosal cells were collected for DNA extraction and subjected to polymerase chain reaction for studying insertion/deletion in the 5-HTT gene-linked polymorphic region. Cross tabulations followed by Chi-square tests were performed to compare the significance of findings, P < 0.05 was considered statistically significant. The LS genotype was the most common genotype found in the subjects with aphthous stomatitis (60%) and controls (40%). The total percentage of LS and SS genotypes and the frequency of S allele were found to be higher in the subjects with aphthous stomatitis as compared to the control group although a statistically significant correlation could not be established, P = 0.144 and 0.371, respectively. Within the limitations of this study, occurrence of RAS was not found to be associated with polymorphic promoter region in serotonin transporter gene.

Candidate genes for alcohol dependence: A genetic association study from India.

Background & objectives:Search for candidate genes for alcohol dependence (AD) has been inconsistent and inconclusive. Moreover, most of the research has been confined to a few specific ethnic groups. Hence, the aim of our study was to explore specific candidate genes for AD in north Indian male population.Methods:In this clinic-based genetic association study, 210 males with AD and 200 controls matched for age, gender and ethnicity were recruited from the clinic and the general population, respectively. Cases were diagnosed with Semi-structured Assessment for Genetics of Alcoholism-II (SSAGA-II). Single-nucleotide polymorphism genotyping was done by real-time quantitative-polymerase chain reaction (PCR) using Taq Man assay (ABI 7500) fast real-time PCR system.Results:Both at the genotypic level and at allelic frequency, Met158 variant of catechol-O-methyl transferase (COMT) showed significant increase in cases as compared to controls. The frequency of heterozygous genotype (A/G) of gamma-aminobutyric acid receptor A1 (GABRA1) was significantly lower in cases as compared to controls. Likewise, for GABRA2, the frequency of homozygous recessive genotype (G/G) was significantly higher in the control group. With respect to the 5-hydroxytryptamine (5HT) transporter long promoter region (5HTTLPR), cholinergic receptor muscarinic (CHRM2) and alcohol dehydrogenase 1B (ADH1B) genes, there was no significant difference between the cases and the controls. Aldehyde dehydrogenase (ALDH2) gene was found to be monomorphic in our study population.Interpretation & conclusions:Our study findings showed COMT polymorphism conferring risk and GABRA polymorphism as a protective genotype for Indian male with AD. Genes for alcohol metabolism, serotonin transporter and cholinergic receptor gene polymorphism were perhaps not contributory to AD for Indian population.

Effects of serotonin transporter gene polymorphism on mood during the period before the competition in Japanese ballet dancers

Effects of serotonin transporter gene polymorphism on mood during the period before the competition in Japanese ballet dancers

Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome.

Serotonin (5-HT) and the serotonin transporter (SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome (IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mRNA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microRNAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.

Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study.

BackgroundDepression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear.MethodsWe evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms–and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors.ResultsTwo hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S′S′ carriers showed an increased risk of depressive symptoms (ORadj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (ORadj = 2.49, p < .001), age (ORadj = 1.19, p = .007), a history of depression (ORadj = 4.73, p < .001), and comorbidity (ORadj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L′L′ carriers, while antidepressant intake was directly related to GDS≥5 in the L′S′ carriers (ORadj = 2.46, p = .036) and borderline significant in the S′S′ carriers (ORadj = 2.41, p = .081).DiscussionThe S′S′ genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S′S′ genotype, compared with the environment, exerted a predominant effect on depressive symptoms, suggesting that it reduces the efficacy of antidepressant therapy. We conclude that genetics may be an important risk factor for depressive symptoms in late adulthood.

Serotonin transporter gene polymorphism modulates inflammatory cytokine responses during acute stress

Cytokines are important mediators of various stress-related modulations of immune function. A major genetic factor determining inter-individual differences in stress reactivity is polymorphisms of the serotonin (5-hydroxytryptamine, 5HT) transporter (5HTT) gene. A short (S) variant, compared with a long (L) variant, of the promoter region of the 5HTT gene-linked polymorphic region (5HTTLPR) has been related to emotional and stress hyper-reactivity. The present study examined whether the 5HTTLPR can modulate responses of inflammatory cytokines under acute stress. Nine Japanese male participants carrying two copies of the S alleles and nine Japanese males carrying S and L alleles underwent the Trier Social Stress Test (TSST). Inflammatory cytokines, endocrine parameters, heart rate and subjective stress were measured before, during and after the task. The participants carrying the SS alleles, but not those carrying the SL alleles, showed a significant increase of IL-1β immediately after TSST. This hyper-reactivity to acute stress in individuals with the SS alleles was also observed in their heart rate and cortisol levels. These results suggest that the S allele of the 5HTTLPR is consistently associated with stress reactivity in multi-level stress-related biological systems.

5-HTTLPR Genotype Moderates the Effects of Past Ecstasy Use on Verbal Memory Performance in Adolescent and Emerging Adults: A Pilot Study.

ObjectiveEcstasy use is associated with memory deficits. Serotonin transporter gene (5-HTTLPR) polymorphisms have been linked with memory function in healthy samples. The present pilot study investigated the influence of 5-HTTLPR polymorphisms on memory performance in ecstasy users, marijuana-using controls, and non-drug-using controls, after a minimum of 7 days of abstinence.MethodData were collected from 116 young adults (18–25 years-old), including 45 controls, 42 marijuana users, and 29 ecstasy users, and were balanced for 5-HTTLPR genotype. Participants were abstinent seven days prior to completing memory testing. Three MANCOVAs and one ANCOVA were run to examine whether drug group, 5-HTTLPR genotype, and their interactions predicted verbal and visual memory after controlling for gender, past year alcohol use, other drug use, and nicotine cotinine levels.ResultsMANCOVA and ANCOVA analysis revealed a significant interaction between drug group and genotype (p = .03) such that ecstasy users with the L/L genotype performed significantly worse on CVLT-2 total recall (p = .05), short (p = .008) and long delay free recall (p = .01), and recognition (p = .006), with the reverse pattern found in controls. Ecstasy did not significantly predict visual memory. 5-HTTLPR genotype significantly predicted memory for faces (p = .02); short allele carriers performed better than those with L/L genotype.Conclusions 5-HTTLPR genotype moderated the effects of ecstasy on verbal memory, with L/L carriers performing worse compared to controls. Future research should continue to examine individual differences in ecstasy’s impact on neurocognitive performance as well as relationships with neuronal structure. Additional screening and prevention efforts focused on adolescents and emerging adults are necessary to prevent ecstasy consumption.

Genetic moderation of the association between adolescent romantic involvement and depression: Contributions of serotonin transporter gene polymorphism, chronic stress, and family discord.

Studies support a link between adolescent romantic involvement and depression. Adolescent romantic relationships may increase depression risk by introducing chronic stress, and genetic vulnerability to stress reactivity/emotion dysregulation may moderate these associations. We tested genetic moderation of longitudinal associations between adolescent romantic involvement and later depressive symptoms by a polymorphism in the serotonin transporter linked polymorphic region gene (5-HTTLPR) and examined contributory roles of chronic stress and family discord. Three hundred eighty-one youth participated at ages 15 and 20. The results indicated that 5-HTTLPR moderated the association between age 15 romantic involvement and age 20 depressive symptoms, with strongest effects for short homozygotes. Conditional process analysis revealed that chronic stress functioned as a moderated mediator of this association, fully accounting for the romantic involvement-depression link among short/short genotypes. Also, romantic involvement predicted later depressive symptoms most strongly among short-allele carriers with high family discord. The results have important implications for understanding the romantic involvement-depression link and the behavioral and emotional correlates of the 5-HTTLPR genotype.

Childhood emotional and sexual maltreatment moderate the relation of the serotonin transporter gene to stress generation.

Emerging evidence suggests that the tendency to generate stressful life events may be, at least in part, genetically determined. However, the role of the early environment in shaping responses to later stressors is crucial to fully specifying biogenetic models of stress generation. The current study examined the moderating role of childhood emotional, physical, and sexual maltreatment on the relation of the serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism of the serotonin transporter gene to proximal independent, dependent, and dependent-interpersonal life events. This question was tested in a cross-sectional community sample of 297 adolescents and young adults. Childhood maltreatment history and proximal life events were assessed with state-of-the-art interviews that provide independent and standardized ratings of the environmental context. Consistent with the stress generation hypothesis, individuals with the risk s-allele of the serotonin transporter gene reported significantly higher rates of dependent and dependent-interpersonal life events than those homozygous for the l-allele, but only in the context of a history of maternal emotional maltreatment or sexual maltreatment. Neither serotonin transporter gene polymorphisms or childhood maltreatment, or their interaction, were associated with reports of independent life events. The current results demonstrate the importance of considering specificity in the early environmental context when examining the relation of genetic factors to the generation of proximal stress.

Serotonin transporter gene polymorphisms: Relation with platelet serotonin level in patients with primary Sjogren's syndrome

Significantly lower platelet serotonin level (PSL) in patients with primary Sjogren's syndrome (pSS) than in healthy controls has been reported in our prior studies. In the present report, we demonstrated effect of functional polymorphisms in the serotonin transporter gene (5-HTT) on PSL. We describe a group of 61 pSS patients and 100 healthy individuals subjects, who received PSL measurement in our prior study. All subjects were genotyped for the promoter 5-HTTLPR (L/S), rs25531 (A/G) and intronic 5-HTTVNTRin2 (l/s) polymorphisms. Overall, the presence of 5-HTTVNTRin2 ss genotype was associated with significantly lower PSL in pSS patients, not in healthy controls. Reduced PSL in pSS patients is in line with hypothesis of association between chronic immunoinflammation and 5-HT system dysregulation, identifying additional mechanisms such as altered 5-HT transport as potential genetic factor contributing to PSL depletion.

Serotonin transporter gene polymorphism (5-HTTLPR) influences trait anxiety by modulating the functional connectivity between the amygdala and insula in Han Chinese males.

A functional polymorphism (5-hydroxytryptamine transporter linked polymorphic region [5-HTTLPR]) in the promoter region of human serotonin transporter gene has been found to be associated with several dimensions of neuroticism and psychopathology, especially anxiety. However, the neural basis underlying the association between 5-HTTLPR and anxiety is less clear. Here, we explored how 5-HTTLPR influenced anxiety by modulating the spontaneous brain activities in Han Chinese. First, we found an association between 5-HTTLPR and anxiety only in the male and not in the female population, where male S/S homozygotes had a significantly higher level of anxiety than male L allele carriers. Then, we examined how 5-HTTLPR influenced anxiety at both regional and network levels in the brain at rest. At the regional level, we found a significantly higher fractional amplitude of low-frequency fluctuations in the amygdala in male S/S homozygotes relative to male L allele carriers. At the network level, male S/S homozygotes showed a weaker resting-state functional connectivity (RSFC) between the amygdala and various regions, including the insula, Heschl's gyrus, lateral occipital cortex, superior temporal gyrus, and hippocampus, and a stronger RSFC between the amygdala and various regions, including the supramariginal gyrus and middle frontal gyrus. However, at both levels, only was the amygdala-insula RSFC correlated with anxiety. Mediation analyses further revealed that the amygdala-insula RSFC mediated the association between 5-HTTLPR and anxiety. In short, our study provided the first empirical evidence that the amygdala-insula RSFC served as the neural basis underlying the association between 5-HTTLPR and anxiety, suggesting a potential neurogenetic susceptibility mechanism for anxiety.