The important effect of 5-HTTLPR polymorphism on the risk of depression in patients with coronary heart disease: a meta-analysis.

BACKGROUND: Depression has been recognized as an independent risk factor of coronary heart disease (CHD). Moreover, there is interrelationship of both depression and CHD. However, the potential pathophysiological mechanisms remain unknown. It might be influenced by genetic and environmental factors. According to recent researches, there is potential association between serotonin transporter gene-linked polymorphic region (5-HTTLPR) polymorphism and risk of depression in CHD patients, but the results are still inconclusive. Therefore, we performed this meta-analysis based on unadjusted and adjusted data to ascertain a more precise conclusion. METHODS: We searched relevant articles through PubMed, Embase, Web of Science, Chinese BioMedical Literature (CBM) and Chinese National Knowledge Infrastructure (CNKI) databases up to August 26, 2019. Study selection and data extraction were accomplished by two authors independently. The strength of the correlation was assessed via odds ratios (ORs) with their 95% confidence intervals (95%CIs). RESULTS: This meta-analysis enrolled six observational studies. Based on unadjusted data, there was significant relationship between 5-HTTLPR polymorphism and depression risk in CHD patients under all genetic models (S vs. L: OR = 1.31, 95%CI = 1.07-1.60; SS vs. LL: OR = 1.73, 95%CI = 1.12-2.67; LS vs. LL: OR = 1.47, 95%CI = 1.13-1.92; LS + SS vs. LL: OR = 1.62, 95%CI = 1.25-2.09; SS vs. LL + LS: OR = 1.33, 95%CI = 1.02-1.74). The results of adjusted data further strengthened this relationship (SS vs. LL: OR = 1.89, 95%CI = 1.28-2.80; LS vs. LL: OR = 1.69, 95%CI = 1.14-2.51; LS + SS vs. LL: OR = 1.80, 95%CI = 1.25-2.59). Subgroup analyses based on ethnicity and major depressive disorder revealed similar results to that of the overall analysis. No evidence of publication bias was observed. CONCLUSIONS: Our results suggest that 5-HTTLPR polymorphism may have an important effect on the risk of depression among patients with CHD, and carriers of the S allele of 5-HTTLPR are more vulnerable to depression.

The 5-HTTLPR polymorphism of the serotonin transporter gene and child's sex moderate the relationship between disaster-related prenatal maternal stress and autism spectrum disorder traits: The QF2011 Queensland flood study.

The 5-HTTLPR polymorphism of the serotonin transporter has been shown to play a role in autism spectrum disorders (ASD). Moreover, disaster-related prenatal maternal stress (PNMS) has also been shown to be associated with ASD. However, no study to date has examined whether these two factors, either individually or in combination, are predictive of ASD traits in the same sample. We hypothesized that children, particularly boys, with the LL genotype exposed to high levels of disaster-related PNMS would exhibit higher levels of ASD traits compared to boys with the LS or SS genotypes and girls regardless of genotype. Genotype and ASD levels obtained using the Australian normed Autism Spectrum Rating Scales - Short Form were available for 105 30-month-old children exposed to varying levels of PNMS following the 2011 Queensland Flood. For boys, higher ASD traits were associated with the 5-HTTLPR LL genotype in combination with either a negative maternal appraisal of the flood, or high levels of maternal composite subjective stress, PSTD-like or peritraumatic dissociation symptoms. For girls, maternal peritraumatic dissociation levels in combination with the 5-HTTLPR LS or SS genotype were associated with higher ASD traits. The present findings are the first to demonstrate that children's genotype moderates effects of disaster-related PNMS on ASD traits, with different pattern according to child sex.

Tackling Missing Heritability by Use of an Optimum Curve: A Systematic Review and Meta-Analysis.

Missing heritability is a common problem in psychiatry that impedes precision medicine approaches to autism and other heritable complex disorders. This proof-of-concept study uses a systematic review and meta-analysis of the association between variants of the serotonin transporter promoter (5-HTTLPR) and autism to explore the hypothesis that some missing heritability can be explained using an optimum curve. A systematic literature search was performed to identify transmission disequilibrium tests on the short/long (S/L) 5-HTTLPR polymorphism in relation to autism. We analysed five American, seven European, four Asian and two American/European samples. We found no transmission preference in the joint samples and in Europe, preferential transmission of S in America and preferential transmission of L in Asia. Heritability will be underestimated or missed in genetic association studies if two alternative genetic variants are associated with the same disorder in different subsets of a sample. An optimum curve, relating a multifactorial biological variable that incorporates genes and environment to a score for a human trait, such as social competence, can explain this. We suggest that variants of functionally related genes will sometimes appear in fixed combinations at both sides of an optimum curve and propose that future association studies should account for such combinations.

Stress Processes Linking Parent-Child Disconnection to Disease Risk in Young Adulthood: Amplification by Genotype.

Previous studies have documented that early stressful family relationships influence subsequent stressful life circumstances and health outcomes over the life course. Less is known, however, about whether stressful parent-child relationships increase the influence of proximal stressors on youth health operating as a stress-sensitizing life context, and individual genetic variations have effects on these developmental processes. Informed by life course stress process theory, which focuses on the proliferation, accumulation, and interactions of stressors over the life course as health risks, we examined whether (a) parent-child disconnection influences the occurrence of stressful life events in young adulthood, (b) parent-child disconnection potentiates the impact of stressful life events on young adults' health, or (c) potential health impact is intensified further by individual genotype. Using longitudinal data from a nationally representative sample of 11,290 adolescents (Mean age 15.5 years, 53% female) over a period of 13 years, we found parent-child disconnection influenced young adults' stressful life events and amplified the impact of stressful life events on cardio-metabolic disease risk. We also found the association between stressful life events and cardio-metabolic disease risk was further intensified by the 5-HTTLPR polymorphism. Our findings demonstrate that stressful family relationships not only initiate stress processes over the early life course, but also sensitize youth to stressors, and that 5-HTTLPR polymorphism interacts with stressful life experiences to predict heightened disease risk.

Associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence: A systematic review and meta-analysis.

OBJECTIVE: The neurotransmitter serotonin is understood to control mood and drug response. Carrying a genetic variant in the serotonin transporter gene (5HTT) may increase the risk of major depressive disorder and alcohol dependence. Previous estimates of the association of the S allele of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence have been inconsistent. METHODS: For the systematic review, we used PubMed MEDLINE and Discovery of The University of Melbourne to search for all relevant case-control studies investigating the associations of 5HTTLPR polymorphism with major depressive disorder and alcohol dependence. Summary odds ratios (OR) and their 95% confidence intervals (CI) were estimated. To investigate whether year of publication, study population or diagnostic criteria used were potential sources of heterogeneity, we performed meta-regression analyses. Publication bias was assessed using Funnel plots and Egger's statistical tests. RESULTS: We included 23 studies of major depressive disorder without alcohol dependence containing 3392 cases and 5093 controls, and 11 studies of alcohol dependence without major depressive disorder containing 2079 cases and 2273 controls. The summary OR for homozygote carriers of the S allele of 5HTTLPR polymorphism compared with heterozygote and non-carriers combined (SS vs SL+LL genotype) was 1.33 (95% CI = [1.19, 1.48]) for major depressive disorder and 1.18 (95% CI = [1.01, 1.38]) for alcohol dependence. The summary OR per S allele of 5HTTLPR polymorphism was 1.16 (95% CI = [1.08, 1.23]) for major depressive disorder and 1.12 (95% CI = [1.01, 1.23]) for alcohol dependence. Meta-regression models showed that the associations did not substantially change after adjusting for year of publication, study population and diagnostic criteria used. There was no evidence for publication bias of the studies included in our meta-analysis. CONCLUSIONS: Our meta-analysis confirms that individuals with the homozygous S allele of 5HTTLPR polymorphism are at increased risks of major depressive disorder as well as alcohol dependence. Further studies are required to investigate the association between 5HTTLPR polymorphism and the comorbidity of major depressive disorder and alcohol dependence as well as gene × environmental interactions.

The association between 5-HTTLPR gene polymorphism and behavioral inhibition in Chinese toddlers.

As one of the fundamental individual characteristics, behavioral inhibition in early childhood has considerable implications for the development of social, cognitive, and psychological adjustment. The purpose of this study was to examine the relation between the 5-HTTLPR polymorphism and behavioral inhibition in Chinese children using a cross-sectional design. A sample of 263 2-year-old children (134 boys and 129 girls of Han ethnicity; ages ranging from 24 to 26 months) in China participated in the study. Behavioral inhibition was assessed through laboratory observations, and genomic DNA was collected with buccal swabs. The results of analysis of covariance (ANCOVA) indicated that the homozygous short 5-HTTLPR allele was associated with lower levels of behavioral inhibition, which was different from most of the findings based on individuals in Western countries. The results suggest that social and cultural factors may be involved in shaping links between the 5-HTTLPR polymorphism and children's specific behaviors.

Subclinical hypomanic experiences in young adults after sleep deprivation are independent of depressive disorders, chronotype or 5-HTTLPR polymorphism.

INTRODUCTION: The acute antidepressant effect of sleep deprivation (SD) in patients with depressive disorders has been studied for more than 60 years. However, hypomanic mood swings after partial or total SD have also been described in people without diagnosed mental disorders. Studying this phenomenon in the general population may yield insights about the mechanisms of therapeutic SD, mania and bipolar disorders. METHODS: A cross-sectional sample of young adults was recruited and classified into those who described having regularly occurring subclinical hypomanic experiences (ROHE) after SD and those who did not. History of psychiatric and physical illness, with screening for depression and mania, as well as alcohol or drug consumption, family history of depressive disorders or suicide, 5-HTTLPR polymorphism, and MEQ-SA chronotype were collected. RESULTS: A total of 251 participants were included; 39.0% indicated regularly having subclinical hypomanic experiences after SD. These experiences were not associated with depressive or mania screening, history of psychiatric illness, family history, 5-HTTLPR polymorphism, or MEQ-SA chronotype. CONCLUSIONS: ROHE after non-therapeutic SD seem to be a relatively common phenomenon in young adults, independent of depressive mood state. Our results suggest that therapeutic SD may depend on a physiological phenomenon of subclinical affective disturbance after SD that affects a part of the general population, independent of psychiatric diagnosis. Further studies could elucidate associated factors and contribute to our understanding of (hypo-)manic mood states.

The Lack of Influence of Homozygous Long Allele of the 5-HTTLPR Gene on the Severity of Alcohol Craving During 6 Weeks of Rehab Hospitalisation in Comparison to Not Homozygous and Homozygous Short Alleles - Preliminary Report.

Purpose: The aim of this study was to assess changes in the severity of alcohol craving according to allelic variants of the 5-HTTLPR gene polymorphism during hospitalisation and their association with selected clinical variables in alcohol-dependent patients. Patients and Methods: The study is exploratory. Participants were investigated at the 2nd and 6th week of alcohol-dependence therapy in the addiction treatment unit. Recruitment was conducted among alcohol-dependent patients from several Polish drug treatment centres. The total sample size was 130 persons (12 females and 118 males). Study subjects' mean age was 43.0 years. Patients were investigated twice by using the Penn Alcohol Craving Scale (PACS) and Beck Depression Inventory (BDI), and once by using Short Alcohol Dependence Data Questionnaire (SADD) and taking a swab for genetic testing. The polymorphism of the gene encoding the serotonin transporter 5-HTTLPR (SLC6A4) was determined from isolated DNA and its homozygous variants of short/short or long/long alleles and heterozygous short/long alleles were analysed. Results: At 6th week of the follow-up, there was a decrease in the severity of alcohol craving in half of subjects with the short/short allele (p = 0.033) and in one-fifth of subjects with the long/short allele (p = 0.002) of the 5-HTTLPR gene. In subjects with long/long allele of the 5-HTTLPR gene, there was no change in the severity of alcohol craving between 2nd and 6th weeks of the study (p = 0.242). Conclusion: There was no statistical influence of the homozygous long allele of the 5-HTTLPR gene on severity of alcohol craving during 6 weeks of rehab hospitalisation in comparison to not homozygous and homozygous short alleles. The s-allele was associated with decrease of alcohol craving. It may point on the potential need for differentiated rehabilitation methods depending on the genetic diversity of addicted patients and its role in the severity of alcohol craving.

5-HTTLPR polymorphism and anxious preoccupation in early breast cancer patients.

BACKGROUND: Difficulties in coping with cancer, and the accompanying anxious and depressive symptoms, have been shown to affect the mood and the quality of life in breast cancer patients. 5-Hydroxytryptamine Transporter Gene-linked Polymorphic Region (5-HTTLPR) functional polymorphism of serotonin transporter has been shown to influence the adaptation to stressful life events. The aim of this prospective study was therefore to examine the association of 5-HTTLPR with the mental adaptation to cancer diagnosis and treatment. PATIENTS AND METHODS: Forty eight consecutive patients with early mammary carcinoma were evaluated at enrolment and at follow up after one and three months. The patients were characterized psychometrically using the Hospital Anxiety and Depression Scale (HADS) and the Mini-Mental Adjustment to Cancer Scale (Mini-MAC); 5-HTTLPR allelic variants were determined using PCR-based techniques. RESULTS: In women with early breast cancer, the mental adaptation to the disease was associated with high scores of avoidance and anxious preoccupation of Mini-MAC, which decreased with time at follow up. Anxious preoccupation decreased with time less in patients with the S/S and S/L genetic variant of 5-HTTLPR as compared with the L/L carriers (p=0.023), indicating gene - environment interactions. CONCLUSIONS: These results indicate that the characterization of 5-HTTLPR allows the identification of breast cancer patients in greater risk of mental suffering, for which specific intervention may be focused; in case of drug therapy, they provide indications for the choice of most appropriate agent in a pharmacogenetic perspective.

Association Study of SLC6A4 (5-HTTLPR) Polymorphism and Its Promoter Methylation with Rehabilitation Outcome in Patients with Subacute Stroke.

Recently it has been suggested that serotonin transporter (SLC6A4) and its 5HTTLPR polymorphism could be involved in post stroke recovery. Here, we characterized the methylation profile of two different CpG islands within the SLC6A4 promoter region in the whole blood of 50 patients with subacute stroke before and after a six-week rehabilitation treatment. These patients were genotyped for 5HTTLPR polymorphism identifying patients on the basis of short (S) and L (L) alleles: 17 patients LL, 22 patients LS and 11 patients SS. At baseline, all CpG sites for both CpG islands displayed a heterogeneous methylation percentage that were not influenced by the different genotypes. After rehabilitation, we found a significant variation in the methylation levels (increase/decrease) in the specific CpG sites of both CpG islands. The statistical analysis showed a significant relationship between the LL, LS and SS alleles and the outcome of the rehabilitation intervention (χ2 (2,50) = 6.395, p = 0.041). Specifically, we found a significant difference between patients with or without a favorable outcome in the LL (11.1% with a favorable outcome) and in the SS (54.4% with a favorable outcome) groups. Our data suggest that 5-HTTLPR polymorphisms and SLC6A4 promoter methylation may be employed as a non-invasive biological marker of recovery in patients with stroke undergoing rehabilitation.

Comprehensive analysis of the 5-HTTLPR allelic polymorphism effect on behavioral and neurophysiological indicators of executive control in people from different ethnic groups in Siberia.

The allelic polymorphism of the serotonin transporter's gene 5-HTTLPR is considered as one of the factors determining an individual genetic predisposition to the development of a wide range of affective disorders, including depression. Many studies have shown that the climatic and social conditions of people's life can have a significant impact on the connections of 5-HTTLPR with the risk of depression. The stop-signal paradigm (SSP) is an experimental method allowing evaluating an individual ability to the self-control of behavior in a changing environment. In the SSP experiment, a subject should either press one of several buttons quickly after the appearance of the target stimuli or suppress the already started movement if an inhibitory signal follows the target stimulus. The aim of this study is a research of associations between the allelic the 5-HTTLPR polymorphism and the individual scores of the personal anxiety level, as well as the behavioral and neurophysiological indicators of the ability to self-control over motor reactions in the SSP. The study was conducted among people from three ethno-regional groups: healthy Caucasoids from Novosibirsk, the Mongoloid groups of the indigenous population of the Tuva Republic and Sakha Republic (Yakutia). Genetic, ethnographic, and psychological influences on an individual's ability to control motor responses were compared. The amplitude of the premotor peak of the evoked brain potential was used as a neurophysiological marker of the person's readiness to the execution of target-directed activity. It was revealed that the frequency of the S-allele polymorphism 5-HTTLPR was significantly higher for both mongoloid groups compared to the Caucasoids. The S/S genotype was associated with an increased level of personal anxiety and at the same time with a better ability to the self-control of behavior in the SSP experiment. Anxiety level, participants' sex, ethnicity, and allelic polymorphism 5-HTTLPR had a statistically significant effect on the amplitude of the premotor readiness potential recorded under the SSP conditions in the frontal and parietal-occipital cortical regions. Our data support the hypothesis that the S/S genotype of the 5-HTTLPR polymorphism may be associated with more success in adapting to the climatic conditions connected with high life risk in comparison to L/L and L/S genotypes.

Post-traumatic Stress Symptoms and Serotonin Transporter (5-HTTLPR) Polymorphism in Breast Cancer Patients.

Introduction: Post-traumatic Symptoms (PTSS) and Post-traumatic Stress Disorder (PTSD) have been reported to affect a quite significant proportion of cancer patients. No study has examined the relationship between serotonin transporter gene-linked polymorphic region (5-HTTLPR) and cancer, including Gene-Environment interactions between this polymorphism and specific causes of distress, such as cancer related problems (CRP) or life stressful events (SLE). Methods: One hundred and forty five breast cancer outpatients participated in the study and were assessed using the Impact of Event Scale (IES), the Problem List (PL) developed by the National Comprehensive Cancer Network (NCCN) Distress Management Guidelines and the Paykel's Life Events Interview to evaluate the exposure to SLE during the year before the cancer diagnosis. Each patient was genotyped for 5-HTTLPR polymorphism by analyzing genomic DNA obtained from whole blood cells. Gene-Environment interactions were tested through moderation analysis. Results: Twenty-six patients (17.7%) were classified as PTSS cases using the IES. Genotype and phenotype distributions did not differ across individuals with/without PTSS (genotype: χ2 = 1.5; df = 2; p = 0.3; phenotype χ2 = 0.9; df = 1; p = 0.2). For both the genotype and phenotype model, using CRP as a predictor showed significant gene-environment interactions with IES total score (p = 0.020 and p = 0.004, respectively), with individuals carrying the l/l allele showing a greater probability of experiencing PTSS. No interaction was found in relationship to SLE (p = 0.750). Conclusion: This study showed a significant GEI between CRP and PTSS in breast cancer patients, with carriers of the l/l allele showing indicators consistent with greater sensitivity to stress.

Depressive Symptoms are Associated with low Serotonin Levels in Plasma but are not 5-HTTLPR Genotype Dependent in Older Adults.

Depressive symptoms are diagnosed by physicians using scales but their pathophysiology is unclear. Low serotonin (5-HT) levels play an important role in depression, and the 5-HT transporter (5-HTT) is an important regulator of plasma serotonin levels and reuptake. Additionally, the 5-HTT gene-linked polymorphic region (5-HTTLPR) is associated with depression. The aim was to clarify the roles of plasma serotonin levels in plasma and the 5HTTPLR polymorphism in depressive symptoms in older adults. A total of 84 older adult participants were evaluated. Depressive symptoms were measured using the Center for Epidemiologic Studies Depression Scale of 20 items (CESD-20). The plasma serotonin levels were determined by ELISA, and the 5-HTTLPR genotype was analyzed by PCR. Depressive symptoms were present in 39.3% (N = 33) of the participants. The median plasma serotonin level was 204.34 ng/mL (SD = 93.88). A significant correlation was found between the CESD-20 scale and plasma serotonin levels (r = -.256; p = .019). Low serotonin levels were associated with the presence of depressive symptoms (p = .001). The 5-HTTLPR analysis showed that of the 84 older adults, 35.7% had the SS genotype, 10.7% had the LL genotype, and 53.6% were heterozygous. The 5-HTTLPR polymorphism was not associated with depressive symptoms (p = .587) and plasma serotonin levels (p = 0.391). Depressive symptoms correlate with low serotonin levels in plasma, but not with the 5-HTTLPR polymorphism in older Mexican adults.

Association between resilience and a functional polymorphism in the serotonin transporter (SLC6A4) gene: A meta-analysis.

Resilience is a mechanism used by humans to adapt to adverse situations. It is a protective factor against mental health problems. This process can be influenced by environmental and genetic factors. Several genes have been associated with interindividual differences in resilience levels, but the results are inconclusive. Therefore, the aim of this meta-analysis was to evaluate the effect of a functional polymorphism (5-HTTLPR) in the SLC6A4 gene on resilience levels. A search in PubMed, HugeNavigator and Google Scholar databases was carried out and 16 studies about the association of 5-HTTLPR polymorphism and resilience in humans were identified. The OpenMeta[Analyst] program was employed to perform statistical analysis using a random-effects model. The final analysis included 9 studies, for a total of 4,080 subjects. Significant results were found when the standardized mean differences (SMD) of LL and SL carriers were compared, (SMD: -0.087 (confidence interval: -0.166 to -0.008; I 2 : 0 %); P value: 0.031). A significant result was also found in an analysis comparing SS/SL versus LL genotypes (SMD: -0.231; confidence interval: -0.400 to -0.061, P value: 0.008; I 2 : 0 %). This is the first meta-analysis performed to identify the pooled association of a functional polymorphism in the serotonin transporter gene and resilience. The current results suggest that the L/L genotype is associated with resilience. Further studies are necessary to elucidate the role of genetics on the resilience mechanisms.

Investigation of the Association between 5-Hydroxytryptamine Transporter Gene-Linked Polymorphic Region with Type 2 Diabetes Mellitus, Obesity and Biochemical Profiles of Serum in Iranian Population.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a serious problem in the world. 5-Hydroxytryptamine (5-HT, serotonin) plays an important role in obesity, glucose control and insulin resistance. The polymorphism of the serotonin transporter gene linked promoter region (5-HTTLPR) might influence 5-HTT expression and serotonin uptake. The polymorphism results in two alleles of L (Long) and S (Short). The aim of the present study was to evaluate the association between 5-HTTLPR genotypes in type 2 diabetes mellitus (T2DM), obesity as well as serum biochemical profiles in Iranian population from 2012 until 2015. METHODS: 180 patients with T2DM and 180 controls were selected and the frequency of S and L alleles was determined by PCR. Then, the relationship between genotypes, body mass index (BMI) and serum biochemical variables was investigated. RESULTS: The frequency of S and L alleles in experimental and control groups was the same [for the L allele p=0.754, OR (95%CI)=1.103 (0.597 to 2.041) and for the S allele p=0.906, OR (95%CI)=(0.490 to 1.676)]. However, the mean triglyceride, cholesterol, LDL-C, systolic and diastolic blood pressure levels in the diabetic subjects with LL genotype were significantly higher than LS and SS genotypes (p<0.001) in this population. CONCLUSION: The L allele of 5-HTTLPR was related to the increased serum lipids and blood pressure in the diabetic patients. However, there was no relationship between the polymorphism of 5-HTTLPR L/S and T2DM in Iranian population.

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

OBJECTIVE: To explore the separate and joint associations of childhood adversities and 5-HTTLPR polymorphism as risk factors for substance use disorders among adults. : Design : Retrospective case-control study. SETTING: Cases from the substance unit and controls from a representative sample of the adult general population in the metropolitan area of Murcia (Spain). PARTICIPANTS: Cases were defined as outpatients 18 years old or older currently in the treatment for alcohol, opioids or cocaine use disorders in the clinical unit. Controls were randomly selected among individuals without substance use disorders who participated in the Psychiatric Enquiry to General Population in Southeast Spain-Murcia (PEGASUS-Murcia) project, a cross-sectional study of a representative sample of the adult general population. In all, 142 cases and 531 controls were interviewed and a subsample of 114 cases (80.3%) and 329 controls (62%) provided a biological sample. EXPOSURE: A history of 12 childhood adversities, lifetime mental disorders and sociodemographic variables was assessed with the Composite International Diagnostic Interview (CIDI)version 3.0). Buccal swabs were obtained to genotype the 5-HTTLPR polymorphism with the biallelic and the triallelic classification. MAIN OUTCOME AND MEASURE: Multivariable logistic regression models were performed to estimate adjusted ORs and 95% CI. RESULTS: Childhood adversities were associated with an elevated risk of substance use disorders (OR=5.77, 95% CI 3.46 to 9.61). Homozygotes for the short allele of the 5-HTTLPR polymorphism also showed the elevated risk of substance use disorders for the biallelic and triallelic classification: (1.97 (1.10 to 3.55) and 2.01 (1.11 to 3.64), respectively). No evidence for gene × environment interactions was found. CONCLUSIONS: Childhood adversities and the 5-HTTLPR polymorphism are involved in the aetiology of substance use disorders though findings exploring the existence of a gene-environment interaction were inconclusive.

A preliminary association study between serotonin transporter (5-HTTLPR), receptor polymorphisms (5-HTR1A, 5-HTR2A) and depression symptom-clusters in a north Indian population suffering from Major Depressive Disorder (MDD).

INTRODUCTION: Major Depressive Disorder (MDD) is a broad heterogeneous diagnostic construct. Previous studies have shown that it can be resolved into several symptom-clusters which are proposed to be associated with single nucleotide polymorphisms (SNPs) of the serotonergic pathway (5-HTTLPR, 5HTR1A, 5-HTR2A). METHODS AND MATERIAL: In a cross-sectional study conducted at a tertiary level mental health care set-up in north India, 80 out-patients with MDD were evaluated with Montgomery Asberg Depression Rating Scale (MADRS) and then genotyping was done. The different clinical and genetic variables were compared across the factor structures of MADRS. Also, the comparison of the genetic data of cases was done with the pre-existing database of the non-blood related healthy ethnically-matched controls. RESULTS: There was no significant association between age, gender, other clinical variables, SNPs like 5-HTTLPR SS/SL, rs6295 CC/CG/GG, rs6311GG/GA/AA, rs6313 CC/CT/TT and different factor-structures like 'detachment' consisting of items like concentration difficulty, lassitude, inability to feel; 'psychic anxiety' consisting of suicidal thoughts and inner tension; 'mood-pessimism' consisting of symptoms like apparent sadness, reported sadness, pessimistic thoughts and 'vegetative symptoms' like decreased sleep, poor appetite. Neither there was any association between genotype of the cases compared with the controls. CONCLUSIONS: No significant association was obtained between the four-factor structures of depression in MADRS and serotonin transporter and receptor SNPs in a study with a small sample size. This study evaluates whether depression symptom-clusters have distinct genotypic determinants and necessitates more comprehensive studies for unravelling the genetic determinants of depression.

Gender-specific association between serotonin transporter polymorphisms (5-HTTLPR and rs25531) and neuroticism, anxiety and depression in well-defined healthy Han Chinese.

BACKGROUND: A tri-allelic serotonin transporter promoter polymorphism (5-HTTLPR/rs25531) more effectively determines the levels of transcriptional efficacy than that with the bi-allelic 5-HTTLPR polymorphism in vitro. Both are reportedly associated with personality traits of negative emotionality, but with conflicting findings. One explanation for this is that a gender difference may play a role in genetic contribution. Here, we hypothesized that the tri-allelic genotype of the serotonin transporter is more closely linked to neuroticism, an anxiety- and depression-related trait, than the bi-allelic variation, particularly in a gender-dependent way. METHODS: The genotypes of the 5-HTTLPR and rs25531 loci were determined in 1139 well-defined physically and mentally healthy Han Chinese (550 men, 589 women; mean age 38.3±10.3 years). All participants completed the neuroticism measure of the short-form Maudsley Personality Inventory (MPI). The levels of anxiety and depression were assessed by the Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI), respectively. RESULTS: A significant tri-allelic genotype-by-gender interaction effect was found in the MPI-neuroticism measure. S'S' homozygotes were associated with higher neuroticism than L' allele carriers in men. Also, both the BAI and BDI scores were higher in the S'S' homozygotic men. In the bi-allelic analyses, however, there was only an association between SS genotype and MPI-neuroticism in men. LIMITATIONS: Sub-analyses by gender-stratification may reduce the statistical power. CONCLUSIONS: Our findings confirm that gender differences exist in the genetic contributions of the serotonin transporter in human neuroticism, and anxiety/depression. Our data provide further support for rs25531, strengthening the effects of 5-HTTLPR.

A review of 5-HT transporter linked promoter region (5-HTTLPR) polymorphism and associations with alcohol use problems and sexual risk behaviors.

Alcohol use and sexual risk behaviors are multidimensional phenomena involving many genetic and environmental factors. 5-HT transporter linked promoter region (5-HTTLPR) polymorphism constitutes an important factor affecting alcohol use problems and risky sexual behaviors. This paper narratively reviews studies on 5-HTTLPR polymorphism and its associations with alcohol use problems and sexual risk behaviors. We searched the electronic databases, PubMed, Ovid, and Google Scholar for articles using MeSH terms. Relevant articles were reviewed and eligible articles were selected for the study. Many studies have reported a significant but moderate association between 5-HTTLPR polymorphism and alcohol use problems. These studies have implicated the presence of at least one S allele to be associated with significant increases in alcohol use problems. Similarly, some studies associate the S allele with increased sexual risk behaviors. Effective alcohol cessation initiatives and STI/HIV prevention programs should be modified to account for 5-HTTLPR polymorphism before planning interventions; genetic effects could moderate the intervention effect.

Review of the genetic basis of emotion dysregulation in children and adolescents.

Previous evidence suggests that emotion dysregulation may have different biological correlates between adults and children/adolescents. Although the role of genetic factors has been extensively studied in adult-onset emotion dysregulation, the genetic basis for pediatric-onset emotion dysregulation remains elusive. The current review article presents a summary of previous studies that have suggested a few genetic variants associated with pediatric emotion dysregulation. Among these candidate loci, many prior studies have been focused on serotonin transporter promoter gene polymorphism 5-HTTLPR. Certain alleles of the 5-HTTLPR gene polymorphism have been found to be associated with traits associated with emotion dysregulation, such as aggression, affect reactivity, and insecure attachment. Additionally, genetic variants involving dopamine and neurophysiological biomarkers like the COMT Val158Met (rs460) and dopamine receptor D2/ ankyrin repeat and kinase domain containing one polymorphisms may play a role in emotion dysregulation. Inconsistent findings have been noted, possibly due to the heterogeneity in study designs and characteristics of different populations. Further research on the role of genetic predetermination of emotion dysregulation in children and adolescents is warranted.