scholarly journals Life stress, 5-HTTLPR and mental disorder: findings from a 30-year longitudinal study

2011 ◽  
Vol 198 (2) ◽  
pp. 129-135 ◽  
Author(s):  
David M. Fergusson ◽  
L. John Horwood ◽  
Allison L. Miller ◽  
Martin A. Kennedy
Keyword(s):  
Longitudinal Study ◽  
Mental Disorders ◽  
Life Events ◽  
Life Stress ◽  
Additive Models ◽  
Stable Gene ◽  
Environment Interaction ◽  
Adverse Life Events ◽  
Gene Environment ◽  
S Alleles

BackgroundRecent meta-analyses have raised concerns about the replicability of gene × environment interactions involving the serotonin transporter gene (5-HTTLPR) in moderating the associations between adverse life events and mental disorders.AimsTo use data gathered over the course of a 30-year longitudinal study of a New Zealand birth cohort to test the hypothesis that the presence of short (‘s’) alleles of 5-HTTLPR are associated with an increased response to life stress.MethodParticipants were 893 individuals from the Christchurch Health and Development Study who had complete data on: the 5-HTTLPR genotype; psychiatric disorders up to the age of 30; and exposure to childhood and adult adverse life events.ResultsA series of 104 regression models were fitted to four mental health outcomes (depressive symptoms, major depression, anxiety disorder and suicidal ideation) observed at ages 18, 21, 25 and 30 using 13 measures of life-course stress that spanned childhood and adult stressors. Both multiplicative and additive models were fitted to the data. No evidence was found that would support the hypothesis that ‘s' alleles of 5-HTTLPR are associated with increased responsivity to life stressors.ConclusionsThe present findings add to the evidence suggesting that it is unlikely that there is a stable gene × environment interaction involving 5-HTTLPR, life stress and mental disorders.

scholarly journals Life events, first depression onset and the serotonin transporter gene

2006 ◽  
Vol 188 (3) ◽  
pp. 210-215 ◽  
Author(s):  
Kay Wilhelm ◽  
Philip B. Mitchell ◽  
Heather Niven ◽  
Adam Finch ◽  
Lucinda Wedgwood ◽  
...  
Keyword(s):  
Risk Factors ◽  
Major Depression ◽  
Life Events ◽  
Serotonin Transporter ◽  
Serotonin Transporter Gene ◽  
Environment Interaction ◽  
Transporter Gene ◽  
Adverse Life Events ◽  
Gene Environment Interaction ◽  
Gene Environment

BackgroundA relationship between the serotonin transporter gene, adverse events and onset of major depression has been reported.AimsTo replicate a gene × environment interaction in a cohort with longitudinal data for life events, experience of depression, parental bonding and neuroticism.MethodAtthe 25-year follow-up, genomic DNA was obtained from 127 cohort members (mean age 48 years) to determine the genotype of the serotonin transporter gene-linked promoter region (5-HTTLPR). Associations were investigated between the 5-HTTLPR genotype, positive and adverse life events and the gene × environment interaction, and also between the 5-HTTLPR genotype and risk factors for depression.ResultsNo relationship was found between 5-HTTLPR genotype and either risk factors for depression or positive life events. Adverse life events had a significantly greater impact on the onset of depression for individuals with the s/s genotype.ConclusionsThe 5-HTTLPR genotype is a significant predictor of onset of major depression following multiple adverse events. This is one of the more robust findings concerning specific biological risk factors for depression.

Stress sensitization to depression following childhood adversity: Moderation by HPA axis and serotonergic multilocus profile scores

2020 ◽  
pp. 1-15
Author(s):  
Lisa R. Starr ◽  
Catherine B. Stroud ◽  
Zoey A. Shaw ◽  
Suzanne Vrshek-Schallhorn
Keyword(s):  
Genetic Variation ◽  
Life Events ◽  
Hpa Axis ◽  
Life Stress ◽  
Childhood Adversity ◽  
Risk Scores ◽  
Genetic Profile ◽  
Environment Interaction ◽  
Nucleotide Polymorphisms ◽  
Stress Sensitization

Abstract Childhood adversity appears to sensitize youth to stress, increasing depression risk following stressful life events occurring throughout the lifespan. Some evidence suggests hypothalamic–pituitary–adrenal (HPA) axis-related and serotonergic genetic variation moderates this effect, in a “gene-by-environment-by-environment” interaction (G × E × E). However, prior research has tested single genetic variants, limiting power. The current study uses a multilocus genetic profile score (MGPS) approach to capture polygenic risk relevant to HPA axis and serotonergic functioning. Adolescents (N = 241, Mage = 15.90) completed contextual-threat-based interviews assessing childhood adversity and acute life events, and diagnostic interviews assessing depression. Established MGPSs indexed genetic variation linked to HPA axis (10 single nucleotide polymorphisms [SNPs]) and serotonergic (five SNPs) functioning. Results showed significant MGPS × Childhood Adversity × Recent Life Stress interactions predicting depression for both HPA axis and serotonergic MGPSs, with both risk scores predicting stronger Childhood Adversity × Recent Stress interactions. Serotonergic genetic risk specifically predicted sensitization to major interpersonal stressors. The serotonergic MGPS G × E × E was re-tested in an independent replication sample of early adolescent girls, with comparable results. Findings support the notion that genetic variation linked to these two neurobiological symptoms alters stress sensitization, and that gene-by-environment (G × E) interactions may be qualified by environmental exposures occurring at different points in development.

scholarly journals Genetic moderation of environmental risk for depression and anxiety in adolescent girls

2001 ◽  
Vol 179 (2) ◽  
pp. 116-121 ◽  
Author(s):  
Judy Silberg ◽  
Michael Rutter ◽  
Michael Neale ◽  
Lindon Eaves
Keyword(s):  
Life Events ◽  
Structural Equation ◽  
Genetic Factors ◽  
Negative Life Events ◽  
Genetic Effect ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Significant Gene ◽  
Independent Life

BackgroundThere is huge individual variation in people's response to negative life events.AimsTo test the hypothesis that genetic factors moderate susceptibility to the environmentally mediated risks associated with negative life events.MethodThe Virginia Twin Study of Adolescent Behavioral Development (VTSABD) was used to study the effects of independent life events (assessed from maternal interview) on depression/anxiety (assessed from child interview) in 184 same-gender female twin pairs, aged 14–17 years, measured on two occasions.ResultsThere was no genetic effect on the independent negative life events studied. A significant gene–environment interaction was found using structural equation modelling. There was no effect of independent life events on adolescents' depression in the absence of parental emotional disorder, but a significant effect in its presence.ConclusionsThere is an environmentally mediated effect of life events on depression/anxiety. Genetic factors play a significant role in individual differences in susceptibility to these environmentally mediated risks.

Stressful life events in early life and suicidal behaviour

2011 ◽  
Vol 26 (S2) ◽  
pp. 2162-2162
Author(s):  
P.A. Saiz
Keyword(s):  
Life Events ◽  
Suicidal Behaviour ◽  
Life Stress ◽  
Stressful Life Events ◽  
Negative Emotion ◽  
Association Studies ◽  
Stressful Life ◽  
Environment Interaction ◽  
Biological Stress ◽  
S Allele

There is robust evidence that stressful life events (SLE) are associated with an increase in risk of developing depression. However, humans display wide variation in response to adversity. Caspi et al (2003) reported that a functional length polymorphism (5-HTTLPR) in the promoter of the serotonin transporter gene moderated the influence of SLE on depressive symptoms, major depression, and suicidality, suggesting evidences of a gene-by-environment interaction.Neuroimage data from healthy, non-depressed, s allele carriers of the 5-HTTLPR show an exaggerated amygdale response to threatening visual stimuli as well as reduced gray matter volume in limbic regions critical for processing of negative emotion compared with individuals with the LL genotype. These data suggest a potent modulatory effect of the 5-HTTLPR on amygdala reactivity to environmental threat.In recent years, a growing number of molecular genetic studies have focused on the serotonin system, suggesting that this system may be involved in the pathogenesis of suicidal behaviour. Meta-analytic evidences support a link between the s allele of the 5-HTTLPR and the risk of suicidal behaviour. However, several case-control association studies show an association between the short allele and the violence, the number, and the medical lethality of the attempts.On the other hand, recent data suggest that biological stress reactivity, mediated by the hypothalamic-pituitary-adrenocortical axis, might be a plausible mechanism underlying the association between the 5-HTTLPR genotype and exposure to life stress in predicting psychopathology.In this presentation we discuss data regarding the complex relationship between the above mentioned systems, stress, and suicidal behaviour.

scholarly journals Life stress, the dopamine receptor gene, and emerging adult drug use trajectories: A longitudinal, multilevel, mediated moderation analysis

2012 ◽  
Vol 24 (3) ◽  
pp. 941-951 ◽  
Author(s):  
Gene H. Brody ◽  
Yi-Fu Chen ◽  
Tianyi Yu ◽  
Steven R. H. Beach ◽  
Steven M. Kogan ◽  
...  
Keyword(s):  
Drug Use ◽  
Emerging Adults ◽  
Dopamine Receptor ◽  
Life Stress ◽  
Receptor Gene ◽  
Saliva Sample ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Gene Environment ◽  
Status Interaction

AbstractThis study was designed to examine the prospective relations of life stress and genetic status with increases in drug use. African Americans (N = 399) in rural Georgia (Wave 1 mean age = 17 years) provided three waves of data across 27.5 months and a saliva sample from which the dopamine receptor D4 (DRD4) gene was genotyped. Multilevel growth curve modeling analysis indicated that emerging adults manifested the highest escalations in drug use when they reported high life stress and carried an allele of DRD4 with 7 or more repeats (7 + R allele). In addition, emerging adults who reported high life stress and carried the 7 + R allele evinced the largest increases in two proximal risk factors for drug use: affiliations with drug-using companions and drug use vulnerability cognitions. Furthermore, when the Gene × Environment interaction effects on the increases in affiliations with drug-using companions and vulnerability cognitions were entered into the model forecasting drug use, the Life Stress × DRD4 Status interaction on drug use became nonsignificant in the presence of the risk mechanisms. This finding provides an example of “second generation” Gene × Environment interaction research in which the interaction's effects on proximal risk mechanisms account for its effects on outcomes.

Gene–environment interaction

2020 ◽  
pp. 343-358
Author(s):  
Craig Morgan ◽  
Marta Di Forti ◽  
Helen L. Fisher
Keyword(s):  
Mental Disorders ◽  
Environmental Factors ◽  
Statistical Modelling ◽  
Environment Interaction ◽  
Gene Environment Interaction ◽  
Working Definition ◽  
Gene Environment ◽  
Genetic And Environmental Factors ◽  
Definition Of ◽  
Study Designs

For all major mental disorders there are many factors that, in combination and through multiple pathways, increase or decrease the risk of onset. These include, to varying degrees, genetic and environmental factors. This chapter provides an introduction, from an epidemiological perspective, to the study of gene–environment interaction. It begins by providing a working definition of gene–environment interaction, rooted in a sufficient causes framework, and then considers, in turn, the prominent puzzles and challenges, including the statistical modelling of interaction, the main study designs (including strengths and weaknesses), measurement of environmental exposures, and required sample sizes. The chapter concludes with a consideration of the implications of recent advances in genetics for studies of gene–environment interaction.

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