5-HTTLPR Polymorphism Of Serotonin Transporter Gene Research Articles

Dependence of Aging-Related Changes in Background Brain Activity on Serotonin Transporter Gene 5-HTTLPR Polymorphism in Men

The serotonin transporter gene polymorphism is associated with plastic reconstructions of the brain structure and activity throughout life, which depend on the sex and age of the subjects. We studied the characteristics of the association between the serotonin transporter gene 5-HTTLPR polymorphism and the background EEG in healthy young (19–35 years, N = 89) and elderly (55–80, N = 60) men. The EEG power, calculated in individual frequency ranges from Δ- to γ-rhythms inclusively, was analyzed. Although the genotyping identified three alleles (SA, LG, and LA), we considered the division into groups with a high (LA/LA), intermediate (LA/LG, LA/SA), and low transcriptional activity (SA/SA, SA/LG), that were marked as L'/L', S '/L ', and S '/S ', respectively. Age-related differences were found in the association of the serotonin transporter gene 5-HTTLPR polymorphism with the power of the background EEG in θ and α1 frequency ranges. Among the L'/L' and S '/L' genotype carriers, elderly men had lower indices of the θ and α1 rhythm powers than young ones. Genetic differences in the power of these rhythms were detected in older men due to lower values in carriers of the S '/L' genotype as compared with S '/S ' and L'/L'. The results obtained contribute to the understanding of the mechanisms of heterogeneity of age-related reconstructions in the brain activity and related changes in mental and affective functions regulated by serotonergic system of the brain.

The serotonin transporter gene 5-HTTLPR polymorphism is associated with affective psychoses but not with schizophrenia: A large-scale study in the Russian population

BackgroundAffective syndrome is thought to be a key feature that differentiates schizophrenia from schizoaffective disorder (SA) and bipolar disorder with psychotic features (BDP). However genetic underpinnings of these differences remain unresolved. ObjectivesWe compared clinical variables of affective psychoses (SA, BDP and schizophrenia with affective symptoms (AFF SCZ)) and schizophrenia without affective symptoms (non-AFF SCZ) and searched for a genetic variant that may differentiate affective psychosis from non-AFF SCZ. MethodsA total of 2677 subjects, including 831 patients with affective psychosis, 785 patients with non-AFF SCZ and 1061 healthy controls, were used. Clinical symptoms were assessed with the PANSS. The sample was genotyped for 5-HTTLPR polymorphism of the serotonin transporter gene. ResultsThe diagnostic groups differed significantly on demographic and clinical variables. The percentage of men was higher, the current age and age at illness onset were lower in non-AFF SCZ and SA compared to AFF SCZ and BDP. The severity of positive and negative symptoms decreased significantly from group to group in the following manner: non-AFF SCZ>AFF SCZ>SA>BDP. There was the association between 5-HTTLPR polymorphism and affective psychosis (p=0.01). The frequency of the SS genotype was higher in the affective psychosis group compared to non-AFF SCZ and controls. No differences in the genotype distribution were identified between the non-AFF SCZ group and controls. LimitationsDifficulties in the differentiation between non-AFF SCZ and AFF SCZ or SA and between AFF SCZ and SA due to uncertain diagnostic boundaries between these conditions. ConclusionsSA is intermediate between non-AFF SCZ and BDP in the severity of positive and negative symptoms. The first episode patients, carriers of the SS genotype have a higher risk of developing affective psychosis than non-AFF SCZ. This finding carries implications for the prognosis of psychosis outcomes in the first-episode patients.

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.

Serotonin Transporter Gene 5-HTTLPR Polymorphism as a Protective Factor Against the Progression of Post-Stroke Depression.

Polymorphisms in the 5-HTT and BDNF genes are shown to affect their function at the molecular and serum level. Prior work has tried to correlate the polymorphisms with post-stroke depression (PSD), the results nevertheless remain indefinitive. A plausible reason accounting for the uncertainty relates to the small sample of each published trial. In this study, we have performed a comprehensive meta-analysis in order to evaluate the effects of 5-HTT and BDNF polymorphisms (5-HTTLPR, STin2 VNTR, 5-HTR2a 102 T/C, Val66Met) on genetic risk of PSD. Human case-control trials were identified by computer-assisted and manual searches. The article search was performed until October 2014. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the fixed effects meta-analysis to measure the effects 5-HTT and BDNF polymorphisms exerted on PSD. We also performed test of heterogeneity, test of publication bias, and sensitivity analysis to examine the reliability and stability of combined effects. 5-HTTLPR was clearly associated with genetic risk of PSD. The association seemed to be more pronounced in the homozygous model (OR = 0.34, 95% CI = 0.23-0.51, P(Q-test) = 0.63). Both the heterozygous model and the recessive model showed 50% decreased risk of PSD (OR = 0.50, 95% CI = 0.37-0.67, P(Q-test) = 0.91; OR = 0.50, 95% CI = 0.36-0.70, P(Q-test) = 0.43, respectively). Such significant association was also detected for Caucasian and Asian. These results were reliable and stable based on related analyses. Taken together, 5-HTTLPR polymorphism of the 5-HTT gene seems to protect against the occurrence of PSD. Small sample size for the polymorphisms within 5-HTT and BDNF genes may have caused underestimated associations, and a larger study is required to further assess the relations.

The 5-HTTLPR polymorphism modulates the influence on environmental stressors on peripartum depression symptoms

Maternal depression during the peripartum period has an incidence of about 13%. Individuals with specific genetic predispositions are more vulnerable to stressful life events suggesting that exploration of gene-environmental pathways might facilitate the identification of risk factors for peripartum depression. The aim of this study was to evaluate the influence of stressful life events in combination with the serotonin transporter gene 5-HTTLPR polymorphism on peripartum depressive symptoms. In a non-psychiatric cohort of 419 Caucasians, the severity of depression was assessed prospectively during pregnancy (3rd trimester) and the postpartum period (2-3 days and 6-8 months) using the Edinburgh Postnatal Depression Scale. Satisfaction with the partner and exposure to negative life events were evaluated using self-report questionnaires and the genotype of the 5-HTTLPR was assessed. Repeated measures generalized linear models were used to investigate the gene-environment interaction on depressive symptoms across late pregnancy and the postpartum period. The 5-HTTLPR S-allele carrier status predicted late postpartum depressive symptom severity only in the presence of negative life events. This interaction was not observed for depressive symptoms during the 3rd trimester or the early postpartum. In addition, S-allele carrier status increased the negative effects of dissatisfaction with the current partner on depressive symptoms in the late postpartum period. In this non-psychiatric cohort, the 5-HTTLPR interacts with both lifetime and current stressors to influence depressive symptoms in the late post partum period. These findings could have clinical implications by allowing identification of women at higher risk for developing postpartum depressive symptoms.

Bipolar affective disorders and temperaments

Since ancient times has there been knowledge of affective temperaments with descriptions ranging from Hippokrates and Galenus to Kraepelin and Kretschmer (in the early 20th century). Whilst temperament can be broadly defined as “an individual's characteristic or habitual inclination or mode of emotional response”, there are three different underlying concepts of temperament, which are based on (1) psychopathology (e.g. Kretschmer or Akiskal), (2) neurobiology (e.g. Eysenck or Gray) or (3) developmental observations (e.g. Chess or Kagan). Despite some undisputable overlap, it is noteworthy that “temperament” differs significantly from “character” or “personality”. Recent research has confirmed that there is a genetic basis to temperament. For example, links to the serotonin transporter gene 5HTTLPR polymorphism have been made. In regards to temperament other neurobiological systems including the HPA axis have been studied as well as issues of gender, ethnicity and psychosocial factors

Association analyses of the serotonin transporter gene with lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample

The objective of this study was to analyze association of the serotonin transporter gene 5-HTTLPR polymorphism on lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism sample. We conducted family-based association analyses in 1913 Caucasians genotyped for the 5-HTTLPR polymorphism. We found evidence for association of the short allele with depression, but no evidence of association with alcohol dependence. On the basis of the evidence that the effect of this polymorphism may be moderated by stressful life events, we classified individuals for the presence and/or absence of stress, as defined by unemployment, relationship problems, or poor health. The evidence for the association with lifetime depression was limited to the group of individuals who had experienced stress, paralleling the direction of effects originally reported by Caspi and colleagues. No evidence was found for the association with alcohol dependence in either the stress or the no-stress groups.