Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene

@article{Caspi2003InfluenceOL,
  title={Influence of Life Stress on Depression: Moderation by a Polymorphism in the 5-HTT Gene},
  author={Avshalom Caspi and Karen Sugden and Terrie E. Moffitt and Alan H. Taylor and Ian W. Craig and HonaLee Harrington and Joseph L. McClay and Jonathan S Mill and Judith Martin and Antony Braithwaite and Richie Poulton},
  journal={Science},
  year={2003},
  volume={301},
  pages={386 - 389}
}
In a prospective-longitudinal study of a representative birth cohort, we tested why stressful experiences lead to depression in some people but not in others. A functional polymorphism in the promoter region of the serotonin transporter (5-HT T) gene was found to moderate the influence of stressful life events on depression. Individuals with one or two copies of the short allele of the 5-HT T promoter polymorphism exhibited more depressive symptoms, diagnosable depression, and suicidality in… 
The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication.
TLDR
Variation at the 5-HTT moderates the sensitivity of individuals to the depressogenic effects of SLEs largely by producing, in SS individuals, an increased sensitivity to the impact of mild stressors.
Interaction between genetic polymorphisms and stressful life events in first episode depression.
Interaction of Serotonin Transporter Gene-Linked Polymorphic Region and Stressful Life Events Predicts Cortisol Stress Response
TLDR
There was a significant interaction of 5-HTTLPR genotype and SLEs, but this interaction was only significant in younger adults and only when the measured SLES had occurred during the first 5 years of life, suggesting that both age and the specific type of SLE has a role in whether a significant gene–environment interaction is observed.
An interaction between perceived stress and 5HTTLPR genotype in the prediction of stable depressive symptomatology.
TLDR
Analysis of data from the National Longitudinal Study of Adolescent Health (Add Health) indicates that the association between perceived stress and depression is moderated by 5HTTLPR genotype for females, but not for males.
Suppression mediates the effect of 5-HTTLPR by stress interaction on depression.
TLDR
It is shown that individuals homozygous for the long allele respond to stressful events by reappraising their emotional meaning, which may hamper the harmful effect of stress on mental health.
Development of depression: sex and the interaction between environment and a promoter polymorphism of the serotonin transporter gene.
TLDR
The results suggest that both the molecular and the psychosocial mechanisms underlying depression may differ between boys and girls and that males seem to be protected from depression.
A relationship between early life stress and depression : the role of the serotonin transporter gene polymorphism ( 5-HTTLPR ) REVIEW
Early life stress has been associated with many different negative outcomes including adulthood depression. Studies have suggested a role of the serotonin transporter gene polymorphism (5-HTTLPR) in
Stress-related negative affectivity and genetically altered serotonin transporter function: evidence of synergism in shaping risk of depression.
TLDR
The probability that stress-related cognitive vulnerabilities for depression result in symptom formation may be moderated by a neurobiologic phenotype characterized by altered processing of negative emotions associated with variation in 5-HTTLPR.
Interactive effect of stressful life events and the serotonin transporter 5-HTTLPR genotype on posttraumatic stress disorder diagnosis in 2 independent populations.
TLDR
People who had both childhood adversity and adult traumatic events were more likely to develop lifetime PTSD compared with those who experienced either type of adverse event, providing additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors.
Moderating effects of DRD2 on depression
The current study examined whether a dopamine receptor gene (DRD2) TaqIA polymorphism and a serotonin transporter polymorphism (5HTTLPR) moderate the effects of stressful life events on depression,
...
...

References

SHOWING 1-10 OF 23 REFERENCES
Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting
Stressful life events, genetic liability, and onset of an episode of major depression in women.
TLDR
Genetic factors influence the risk of onset of major depression in part by altering the sensitivity of individuals to the depression-inducing effect of stressful life events.
Stressful life events and genetic liability to major depression: genetic control of exposure to the environment?
TLDR
In women, genetic risk factors for MD increase the probability of experiencing SLEs in the interpersonal and occupational/financial domains, and the genetic liability to alcoholism impacted on the risk for being robbed and having trouble with the law.
Serotonin Transporter Genetic Variation and the Response of the Human Amygdala
TLDR
Genetically driven variation in the response of brain regions underlying human emotional behavior is demonstrated and differential excitability of the amygdala to emotional stimuli may contribute to the increased fear and anxiety typically associated with the short SLC6A4 allele.
Genetic and population perspectives on life events and depression
  • G. Brown
  • Psychology
    Social Psychiatry and Psychiatric Epidemiology
  • 1998
Abstract Population comparisons of epidemiological surveys using the same investigator-based measures suggest that large differences are possible in the experience of clinically relevant depression
Diathesis-stress theories in the context of life stress research: implications for the depressive disorders.
TLDR
Advances in the conceptualization and measurement of life stress in the past 2 decades raise several questions concerning traditional diathesis-stress theories of psychopathology, and information is available on diatheses and stress for specific disorders to provide a foundation for more empirically based hypotheses about diathetic-stress interactions.
Role of Genotype in the Cycle of Violence in Maltreated Children
TLDR
A functional polymorphism in the gene encoding the neurotransmitter-metabolizing enzyme monoamine oxidase A was found to moderate the effect of maltreatment, and it was found that Maltreated children with a genotype conferring high levels of MAOA expression were less likely to develop antisocial problems.
Genetic perspectives on the serotonin transporter
Adolescent life events as predictors of adult depression.
...
...