Inhibitory control mediates the interaction between serotonin transporter gene (5-HTTLPR) and peer victimization on adolescent depressive symptoms.
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ABSTRACT:
SUBMITTER: Lin X
PROVIDER: S-EPMC8289840 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe compare the genotype distribution for the serotonin transporter polymorphism (5-HTTLPR) in a sample of older Taiwanese adults with samples of various racial and ethnic groups collected in other studies. We also explore interactions among sex, stressors, and 5-HTTLPR genotype on depressive symptoms in our sample.MethodsUsing a nationally representative sample of 984 Taiwanese aged 53 and older, we model depressive symptoms as a function of 5-HTTLPR genotype and two classes of stressors: lifetime trauma and recent major life events. We test two- and three-way interactions among stressors, 5-HTTLPR, and sex.ResultsThis sample exhibits higher frequency of S/S and lower frequency of L/L genotype than Western samples, but the distribution is comparable to those in East Asian populations. Nearly 9% carry an allele (XL) that has rarely been reported in the literature. Although the gene-environment (GxE) interaction with recent major life events is not significant, our results suggest that trauma has a worse effect on depressive symptoms for those with S/S or S/L genotype than for those who do not carry the S allele (P<0.05). We find no evidence that this GxE interaction varies by sex.ConclusionsPrevious studies of this GxE interaction have been inconclusive, perhaps because interactions between genotype and stressful events are more prominent under extreme stressors. Our findings underscore the need to move beyond a bi-allelic parameterization of the 5-HTTLPR polymorphism and raise questions about why East Asian populations exhibit low rates of depression despite a high frequency of the S allele.
| S-EPMC2841212 | biostudies-literature
Project description:Depressive symptoms are prevalent and rise during adolescence. The present study is a prospective investigation of environmental and genetic factors that contribute to the growth in depressive symptoms and the frequency of heightened symptoms during adolescence. Participants included 206 mother-father-adolescent triads (M age at Time 1 = 13.06 years, SD = .51, 52% female). Harsh parenting was observationally assessed during a family conflict paradigm. DNA was extracted from saliva samples and genotyped for the 5-HTTLPR and BDNF Val66Met polymorphisms. Adolescents provide self-reports of depressive symptoms annually across early adolescence. The results reveal Gene × Environment interactions as predictors of adolescent depressive symptom trajectories in the context of harsh parenting as an environmental risk factor. A BDNF Val66Met × Harsh Parenting interaction predicted the rise in depressive symptoms across a 3-year period, whereas a 5-HTTLPR × Harsh Parenting interaction predicted greater frequency in elevated depressive symptoms. The findings highlight the importance of unique genetic and environmental influences in the development and course of heightened depressive symptoms during adolescence.
| S-EPMC5391309 | biostudies-literature
Project description:We explored the relationship of genetic variants of the serotonin transporter gene SLC6A4, a key regulator of the serotonergic neurotransmission, with both depressive symptoms and plasma interleukin-6 (IL-6) levels.We genotyped 20 polymorphisms in 360 male twins (mean age, 54 years) from the Vietnam Era Twin Registry. Current depressive symptoms were measured with the Beck Depression Inventory II. IL-6 was assessed using a commercially available ELISA kit. Genotype associations were analyzed using generalized estimating equations. To study how SLC6A4 genetic vulnerability influences the relationship between depressive symptoms and IL-6, bivariate models were constructed using structural equation modeling. Of the 20 polymorphisms examined, the effective number of independent tests was 6, and the threshold of significance after Bonferroni correction was 0.008. There were 6 single-nucleotide polymorphisms significantly associated with Beck Depression Inventory (P< or =0.008), including rs8071667, rs2020936, rs25528, rs6354, rs11080122, and rs8076005, and 1 single-nucleotide polymorphism was borderline associated (rs12150214, P=0.017). Of these 7 single-nucleotide polymorphisms, 3 were also significantly associated with IL-6 (P<0.008), including rs25528, rs6354, and rs8076005, and the other 4 were borderline associated (P=0.009 to 0.025). The subjects with 1 copy of the minor allele of these 7 single-nucleotide polymorphisms had higher Beck Depression Inventory scores and IL-6 levels. Further bivariate modeling revealed that approximately 10% of the correlation between Beck Depression Inventory and IL-6 could be explained by the SLC6A4 gene.Genetic vulnerability involving the SLC6A4 gene is significantly associated with both increased depressive symptoms and elevated IL-6 plasma levels. Common pathophysiological processes may link depression and inflammation, and implicate the serotonin pathway in neural-immune interactions.
| S-EPMC2802220 | biostudies-literature
Project description:Peer victimization is a developmentally salient stressor that elevates adolescents' risk for anxiety disorders. However, modifiable mechanisms that explain this link and can be targeted via therapeutic interventions remain poorly understood. Drawing from psychobiological models implicating aberrant threat sensitivity in the development and maintenance of psychopathology, the current study investigated sensitivity to peer-related social threats as a mechanism underlying the association between peer victimization and anxiety. A sample of 197 dyads of early adolescents (M age = 12.02; 46% female) and parents/guardians (M age = 41.46; 90% female) completed online surveys assessing peer victimization, sensitivity to potential (i.e., ambiguous) social threats, and anxiety. Controlling for potentially confounding demographic and psychosocial factors, both self- and parent-reported peer victimization were positively associated with adolescent anxiety symptoms. Additionally, there were significant indirect effects from self- and parent-reported peer victimization to anxiety via social threat sensitivity. Supplemental analyses indicated unique effects of covert, but not overt, peer victimization on social threat sensitivity and anxiety. The findings provide initial evidence that peer victimization experiences lower adolescents' threshold for interpreting threats in ambiguous social situations, which contributes to heightened anxiety. These results implicate social threat sensitivity as a potential therapeutic target for interrupting links from peer victimization to psychological distress.
| S-EPMC10151014 | biostudies-literature
Project description: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.
| S-EPMC8097040 | biostudies-literature
Project description:BackgroundThe psychological and neurobiological processes underlying moral judgment have been the focus of extensive recent research. Here we show that serotonin transporter (5-HTTLPR) genotype predicts responses to moral dilemmas featuring foreseen harm to an innocent.Methodology/principal findingsParticipants in this study judged the acceptability of actions that would unintentionally or intentionally harm an innocent victim in order to save others' lives. An analysis of variance revealed a genotype × scenario interaction, F(2, 63) = 4.52, p = .02. Results showed that, relative to long allele homozygotes (LL), carriers of the short (S) allele showed particular reluctance to endorse utilitarian actions resulting in foreseen harm to an innocent individual. LL genotype participants rated perpetrating unintentional harm as more acceptable (M = 4.98, SEM = 0.20) than did SL genotype participants (M = 4.65, SEM = 0.20) or SS genotype participants (M = 4.29, SEM = 0.30). No group differences in moral judgments were observed in response to scenarios featuring intentional harm.Conclusions/significanceThe results indicate that inherited variants in a genetic polymorphism that influences serotonin neurotransmission influence utilitarian moral judgments as well. This finding is interpreted in light of evidence that the S allele is associated with elevated emotional responsiveness.
| S-EPMC3187753 | biostudies-literature
Project description:Depending on genetic sensitivity to it, stress may affect depressive symptomatology differentially. Applying the stress-diathesis hypothesis to older adults, we postulate: (1) recent stress will associate with increased depressive symptom levels and (2) this effect will be greater for individuals with at least one short allele of the serotonin transporter gene promoter region (5-HTTLPR). Further, we employ a design that addresses specific limitations of many prior studies that have examined the 5-HTTLPR × SLE relation, by: (a) using a within-person repeated-measures design to address fluctuations that occur within individuals over time, increase power for detecting G × E, and address GE correlation; (b) studying reports of exogenous stressful events (those unlikely to be caused by depression) to help rule out reverse causation and negativity bias, and in order to assess stressors that are more etiologically relevant to depressive symptomatology in older adults. The sample is drawn from the Health and Retirement Study, a U.S. population-based study of older individuals (N = 28,248; mean age = 67.5; 57.3 % female; 80.7 % Non-Hispanic White, 14.9 % Hispanic/Latino, 4.5 % African American; genetic subsample = 12,332), from whom measures of depressive symptoms and exogenous stressors were collected biannually (1994-2010). Variation in the 5-HTTLPR was characterized via haplotype, using two single nucleotide polymorphisms (SNPs). Ordered logit models were constructed to predict levels of depressive symptoms from 5-HTTLPR and stressors, comparing results of the most commonly applied statistical approaches (i.e., comparing allelic and genotypic models, and continuous and categorical predictors) used in the literature. All models were stratified by race/ethnicity. Overall, results show a main effect of recent stress for all ethnic groups, and mixed results for the variation in 5-HTTLPR × stress interaction, contingent upon statistical model used. Findings suggest there may be a differential effect of stressors and 5-HTTLPR on depressive symptoms by ethnicity, but further research is needed, particularly when using a haplotype to characterize variation in 5-HTTLPR in population-based sample with a diverse ethnic composition.
| S-EPMC4720538 | biostudies-literature
Project description:Previous studies have shown that peer dysfunction in adolescence predicts depression in adulthood, even when controlling for certain individual- and/or family-level characteristics. However, these studies have not controlled for numerous potential familial confounders, precluding causal inferences. The present study therefore used a sibling comparison design (i.e., comparing siblings within families) to test whether peer dysfunction (e.g., lack of friendships, victimization) in adolescence continues to predict depression in adulthood after accounting for unmeasured familial confounds and individual characteristics in adolescence. Participants' (N = 85) dysfunction with peers was assessed in adolescence (Mage = 13.21, SD = 3.47) by self- and parent-report, and adult depressive symptoms were assessed up to five times, up to 38 years later. Multilevel modeling was used to examine the effect of adolescent peer dysfunction on adult depressive symptoms after adjusting for familial confounds and/or individual characteristics in adolescence (e.g., baseline depressive symptoms, dysfunctional relations with siblings/parents). Both self-reported (b = 1.28, p < 0.001) and parent-reported (b = 0.56, p = 0.032) adolescent peer dysfunction were associated with greater depressive symptom severity in adulthood in unadjusted models. Self-reported (but not parent-reported) adolescent peer dysfunction continued to predict adult depressive symptoms after controlling for familial confounding and measured covariates such as adolescent depressive symptoms and relations with siblings and parents (b = 1.06, p = 0.035). Although confidence intervals were wide and the potentially confounding effects of numerous individual-level factors were not ruled out, these findings provide preliminary evidence that perceived peer dysfunction in adolescence may be an unconfounded risk factor for depressive symptoms in adulthood.
| S-EPMC8854477 | biostudies-literature
Project description:Studying monoaminergic seasonality is likely to improve our understanding of neurobiological mechanisms underlying season-associated physiological and pathophysiological behavior. Studies of monoaminergic seasonality and the influence of the serotonin-transporter-linked polymorphic region (5-HTTLPR) on serotonin seasonality have yielded conflicting results, possibly due to lack of power and absence of multi-year analyses. We aimed to assess the extent of seasonal monoamine turnover and examined the possible involvement of the 5-HTTLPR. To determine the influence of seasonality on monoamine turnover, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) were measured in the cerebrospinal fluid of 479 human subjects collected during a 3-year period. Cosine and non-parametric seasonal modeling were applied to both metabolites. We computed serotonin (5-HT) seasonality values and performed an association analysis with the s/l alleles of the 5-HTTLPR. Depressive symptomatology was assessed using the Beck Depression Inventory-II. Circannual variation in 5-HIAA fitted a spring-peak cosine model that was significantly associated with sampling month (P=0.0074). Season of sampling explained 5.4% (P=1.57 × 10(-7)) of the variance in 5-HIAA concentrations. The 5-HTTLPR s-allele was associated with increased 5-HIAA seasonality (standardized regression coefficient=0.12, P=0.020, N=393). 5-HIAA seasonality correlated with depressive symptoms (Spearman's rho=0.13, P=0.018, N=345). In conclusion, we highlight a dose-dependent association of the 5-HTTLPR with 5-HIAA seasonality and a positive correlation between 5-HIAA seasonality and depressive symptomatology. The presented data set the stage for follow-up in clinical populations with a role for seasonality, such as affective disorders.
| S-EPMC3818011 | biostudies-literature
Project description:BackgroundChild maltreatment (CM) and peer victimization (PV) are serious issues affecting children and adolescents. Despite the interrelatedness of these exposures, few studies have investigated their co-occurrence and combined impact on health outcomes. The study objectives were to determine the overall and sex-specific prevalence of lifetime exposure to CM and past-month exposure to PV in adolescents, and the impact of CM and PV co-occurrence on non-suicidal self-injury, suicidality, mental health disorders, and physical health conditions.MethodsAdolescents aged 14-17 years (n = 2,910) from the 2014 Ontario Child Health Study were included. CM included physical, sexual, and emotional abuse, physical neglect, and exposure to intimate partner violence. PV included school-based, cyber, and discriminatory victimization. Logistic regression was used to compare prevalence by sex, examine independent associations and interaction effects in sex-stratified models and in the entire sample, and cumulative effects in the entire sample.ResultsAbout 10% of the sample reported exposure to both CM and PV. Sex differences were as follows: females had increased odds of CM, self-injury, suicidality, and internalizing disorders, and males had greater odds of PV, externalizing disorders, and physical health conditions. Significant cumulative and interaction effects were found in the entire sample and interaction effects were found in sex-stratified models, indicating that the presence of both CM and PV magnifies the effect on self-injury and all suicide outcomes for females, and on suicidal ideation, suicide attempts, and mental health disorders for males.ConclusionsExperiencing both CM and PV substantially increases the odds of poor health outcomes among adolescents, and moderating relationships affect females and males differently. Continued research is needed to develop effective prevention strategies and to examine protective factors that may mitigate these adverse health outcomes, including potential sex differences.
| S-EPMC9074223 | biostudies-literature