Dataset Information

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

ABSTRACT:

Background

Recent 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.

Aims

To 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.

Method

Participants 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.

Results

A 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.

Conclusions

The 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.

SUBMITTER: Fergusson DM

PROVIDER: S-EPMC3031653 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Publications

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

Fergusson David M DM Horwood L John LJ Miller Allison L AL Kennedy Martin A MA

The British journal of psychiatry : the journal of mental science 20110201 2

<h4>Background</h4>Recent 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.<h4>Aims</h4>To 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.<h4 ...[more]

PMID: 21282783

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Project description:ObjectiveThis study aims to explore the short-term and long-term prevalence and effects of post-traumatic stress disorder (PTSD) among victims of cluster munitions.Design and settingA prospective 10-year longitudinal study that took place in Lebanon.ParticipantsTwo-hundred-and-forty-four Lebanese civilian victims of submunition blasts, who were injured in 2006 and were over 18 years old, were interviewed. Included were participants who had been diagnosed with PTSD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) and the PTSD Checklist - Civilian Version in 2006. Interviewees were present for the 10-year follow-up.Main outcome measuresPTSD prevalence rates of participants in 2006 and 2016 were compared. Analysis of the demographical data pertaining to the association of long-term PTSD with other variables was performed. p Values <0.05 were considered statistically significant for all analyses (95% CI).ResultsAll the 244 civilians injured by cluster munitions in 2006 responded, and were present for long-term follow-up in 2016. The prevalence of PTSD decreased significantly from 98% to 43% after 10 years (p<0.001). A lower long-term prevalence was significantly associated with male sex (p<0.001), family support (p<0.001) and religion (p<0.001). Hospitalisation (p=0.005) and severe functional impairment (p<0.001) post-trauma were significantly associated with increased prevalence of long-term PTSD. Symptoms of negative cognition and mood were more common in the long run. In addition, job instability was the most frequent socioeconomic repercussion among the participants (88%).ConclusionsPsychological symptoms, especially PTSD, remain high in war-affected populations many years after the war; this is particularly evident for Lebanese civilians who were victimised by cluster munitions. Screening programmes and psychological interventions need to be implemented in vulnerable populations exposed to war traumas. Officials and public health advocates should consider the socioeconomic implications, and help raise awareness against the harm induced by cluster munitions and similar weaponry.

Project description:ObjectiveTo conduct a meta-analysis of all published genetic association studies of 5-HTTLPR polymorphisms performed in PTSD cases.Methods data sourcesPotential studies were identified through PubMed/MEDLINE, EMBASE, Web of Science databases (Web of Knowledge, WoK), PsychINFO, PsychArticles and HuGeNet (Human Genome Epidemiology Network) up until December 2011.Study selectionPublished observational studies reporting genotype or allele frequencies of this genetic factor in PTSD cases and in non-PTSD controls were all considered eligible for inclusion in this systematic review.Data extractionTwo reviewers selected studies for possible inclusion and extracted data independently following a standardized protocol.Statistical analysisA biallelic and a triallelic meta-analysis, including the total S and S' frequencies, the dominant (S+/LL and S'+/L'L') and the recessive model (SS/L+ and S'S'/L'+), was performed with a random-effect model to calculate the pooled OR and its corresponding 95% CI. Forest plots and Cochran's Q-Statistic and I(2) index were calculated to check for heterogeneity. Subgroup analyses and meta-regression were carried out to analyze potential moderators. Publication bias and quality of reporting were also analyzed.Results13 studies met our inclusion criteria, providing a total sample of 1874 patients with PTSD and 7785 controls in the biallelic meta-analyses and 627 and 3524, respectively, in the triallelic. None of the meta-analyses showed evidence of an association between 5-HTTLPR and PTSD but several characteristics (exposure to the same principal stressor for PTSD cases and controls, adjustment for potential confounding variables, blind assessment, study design, type of PTSD, ethnic distribution and Total Quality Score) influenced the results in subgroup analyses and meta-regression. There was no evidence of potential publication bias.ConclusionsCurrent evidence does not support a direct effect of 5-HTTLPR polymorphisms on PTSD. Further analyses of gene-environment interactions, epigenetic modulation and new studies with large samples and/or meta-analyses are required.

Dataset Information

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

Background

Aims

Method

Results

Conclusions

Publications

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

Similar Datasets

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