Allele Of 5-HTTLPR Polymorphism Research Articles

Association of Serotonergic Pathway Gene Polymorphisms With Behavioral Parameters in Patients With Opioid Dependence.

Background and aimsOpioid dependence is a chronic, relapsing substance use disorder with a multifactorial etiology, including a genetic component. Serotonin pathway gene polymorphisms have been an important focus of research for psychiatric disorders, including substance use disorders. This study aimed to identify the association of serotonin pathway gene polymorphisms with self-harm, depressive symptoms, impulsiveness, and aggression in patients with opioid dependence.MethodThe study group comprised 366 subjects with opioid dependence and 200 healthy volunteers. Patients were assessed for a history of self-harm, depressive symptoms, impulsiveness, and aggression using standard tools. Genomic DNA was used for genotyping of four polymorphisms - 5-HTTLPR, STin2 VNTR, TPH1 A218C, and TPH2 G703T.ResultsThe short allele of 5-HTTLPR polymorphism showed a significant difference between cases (59.8%) and controls (40.1%) (p=0.001) and revealed an association with age at opioid dependence (p=0.033). There was a borderline significance of the short allele of 5-HTTLPR with the duration of opioid use (p=0.061) and non-plan impulsivity (p=0.076), suggesting a role of 5-HTTLPR in the susceptibility of opioid dependence. The other markers did not differ between cases and controls. However, the STin2A polymorphism revealed a significant association with anger scores, which may indicate its role in aggressive behavior.ConclusionsThe present study, the first of its kind, suggests an association of 5-HTTLPR polymorphism with opioid dependence and STin2A polymorphism with aggressive behavior among opioid-dependence patients, signifying the role of these markers in our patient population.

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

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. 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. 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. 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.

Association of TPH1, TPH2, and 5HTTLPR with PTSD and depressive symptoms

To examine the potential contribution of the serotonin hydroxylase (TPH1 and TPH2) genes, and the serotonin transporter promoter polymorphism (5HTTLPR) to the unique and pleiotropic risk of PTSD symptoms and depressive symptoms. Participants included 200 adults exposed to the 1988 Spitak earthquake from 12 multigenerational families (3 to 5 generations). Severity of trauma exposure, PTSD, and depressive symptoms were assessed using standard psychometric instruments. Pedigree-based variance component analysis was used to assess the association between select genes and the phenotypes. After adjusting for age, sex, exposure and environmental variables, there was a significant association of PTSD symptoms with the 't' allele of TPH1 SNP rs2108977 (p<0.004), explaining 3% of the phenotypic variance. This allele also showed a non-significant trend for an association with depressive symptoms (p=0.08). Also, there was a significant association of PTSD symptoms and the 't' allele of TPH2 SNP rs11178997 (p=0.03), explaining 4% of the variance. Depressive symptoms were significantly associated with the 's' allele of 5HTTLPR (p=0.03), explaining 4% of the variance. Retrospective rating of exposure may have been subject to memory failure leading to misestimation of symptom severities. Second, findings may not be generalizable to other ethnic/racial populations. To our knowledge, this is the first published report showing that variants in TPH1 and TPH2 genes constitute risk factors for PTSD symptoms. Additionally, the TPH1 gene may be associated pleiotropically with PTSD and depressive symptoms. The association of the 's' allele of 5HTTLPR polymorphism with depression adds to similar findings from case/case-control studies.

Associação entre o polimorfismo funcional do promotor ligado ao transportador da serotonina (5-HTTLPR): agressividade externalizada e internalizada e abuso do álcool.

Genetic factors of alcoholism influence the phenotypic heterogeneity of alcohol dependence, allowing the higher or lower expression of related aggressive behaviours. The pathogenesis of alcoholism and anti-social behaviour has been connected to serotonergic system dysfunction, given support to examine the association with 44-basepair insertion/deletion polymorphism of serotonin gene transporter (5-HTT). The study aims to assess the relationship between 5-HHTLPR polymorphism, aggressive behaviour and alcohol consumption pattern. There were recruited 97 alcohol dependent patients from the alcoholism unit (Etilo-Risco) of the Psychiatric Service of Santa Maria Hospital. Blood for DNA extraction and clinical and behavioural information was collected during the therapeutic program. Regarding 5-HTTLPR polymorphism prevalence in alcoholic population, 30.7% were homozygotic to l allele, 19.8% were homozygotic to s allele and 49.5% were heterozygotic l/s. Alcoholic patients carrying the l allele from 5-HTTLPR genotype showed significant lower scores of aggressivity during acute alcohol consumption, and alcoholic patients carrying the s allele showed significant higher scores of aggressivity (during acute alcohol consumption and abstinence), however, the results were not significant. The association between the functional nature of the s allele of 5-HTTLPR polymorphism with aggressive behaviour is in agreement with the general models of aggressivity that report low levels of central serotonergic activity related to impulsive and anti-social behaviours. The results demonstrate an association between 5-HTTLPR polymorphism and the auto and heteroaggressive behaviour in alcohol dependent population, particularly when aggressivity appears under acute alcohol consumption. During acute alcohol consumption stage, the presence of the l allele may act as a protective factor of aggressive behaviour risk, whereas the results tendency showed the s allele as susceptibility factor. Data suggests that the presence of s allele may confer a genetic vulnerability factor to the development of aggressive behaviour in alcohol dependent subjects, specially, in interaction with acute alcohol consumption stage.

Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis

Background There is strong evidence supporting a role for serotonin system dysfunction in the pathology of suicidal behavior. Many studies have examined the association between a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) and suicide but have yielded inconsistent results. Our goal here, by analyzing the cumulative data from primary literature, was to determine conclusively whether there is an association. Methods Three meta-analyses were performed. One compared the 5-HTTLPR polymorphism between suicidal subjects and normal control subjects; another compared suicide attempters with nonattempters of the same psychiatric diagnoses; the last one compared either violent or nonviolent suicidal subjects with normal control subjects. Results We found no association between 5-HTTLPR polymorphism and suicidal behavior ( p = .379). When we compared subjects with the same psychiatric diagnoses, the genotypes carrying the s allele were significantly more frequent in suicide attempters than in nonattempters ( p = .004). In addition, the s allele was associated with violent suicide ( p = .0001) but not with nonviolent suicide ( p = 1.00). Conclusions Our results provide significant evidence supporting the association of the s allele of 5-HTTLPR polymorphism with suicidal behavior in the psychiatric population, also with violent suicide. These support a role for decreased serotonin transporter function in the vulnerability to suicide in a select population.

P.1.026 Serotonin transporter promoter gene polymorphic region (5-HTTLPR) and personality in female patients with seasonal affective disorder and healthy controls

There is strong evidence supporting a role for serotonin system dysfunction in the pathology of suicidal behavior. Many studies have examined the association between a functional polymorphism of the serotonin transporter gene promoter (5-HTTLPR) and suicide but have yielded inconsistent results. Our goal here, by analyzing the cumulative data from primary literature, was to determine conclusively whether there is an association.Three meta-analyses were performed. One compared the 5-HTTLPR polymorphism between suicidal subjects and normal control subjects; another compared suicide attempters with nonattempters of the same psychiatric diagnoses; the last one compared either violent or nonviolent suicidal subjects with normal control subjects.We found no association between 5-HTTLPR polymorphism and suicidal behavior (p = .379). When we compared subjects with the same psychiatric diagnoses, the genotypes carrying the s allele were significantly more frequent in suicide attempters than in nonattempters (p = .004). In addition, the s allele was associated with violent suicide (p = .0001) but not with nonviolent suicide (p = 1.00).Our results provide significant evidence supporting the association of the s allele of 5-HTTLPR polymorphism with suicidal behavior in the psychiatric population, also with violent suicide. These support a role for decreased serotonin transporter function in the vulnerability to suicide in a select population.