Early Family Environment, Current Adversity, the Serotonin Transporter Promoter Polymorphism, and Depressive Symptomatology

Taylor, Shelley E.; Way, Baldwin M.; Welch, William T.; Hilmert, Clayton J.; Lehman, Barbara J.; Eisenberger, Naomi I.

doi:10.1016/j.biopsych.2006.04.019

Cited by 393 publications

(368 citation statements)

References 22 publications

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“…48 Six studies were cross-sectional surveys. 30,31,34,37,39,41,45 One study used a combined cohort/case-control design, selecting participants with extreme scores on either environmental adversity or depression for genotyping. 40 One study examined individuals exposed to a major stressor (myocardial infarction).…”

Section: Methodsmentioning

confidence: 99%

“…The weak or non-significant associations between SLEs and depression in these studies suggest problems with the validity of self-report measures of SLE 50 and, in the study by Gillepie and colleagues 44 possible inaccuracies of the retrospective assessment of depression. 51 Serotonin transporter gene-environment interactionunselected primary care attendees, 37 three studies used convenience samples of students or teachers; 34,35,43 three studies used enriched samples selected based on experience of childhood abuse, 31 high levels of social adversity and depression 40 or extremes on neuroticism 45 and two studies used clinical samples of depressed patients. 33,36 Sample size is a major determinant of power to detect G Â E. 52 It is therefore notable that the two studies with largest samples produced negative findings.…”

Section: Methodsmentioning

confidence: 99%

“…32 Some authors assumed a dominant s based on an early 5-HTT expression study and did not report results separately for heterozygotes. 41 On the other hand, Kendler and colleagues 15 found that a model with recessive s (that is with ll and ls combined) provided best fit to their data and at least one other study showed results consistent with recessive s. 34 Results from child and adolescent samples place heterozygotes intermediate but close to ll homozygotes, suggesting a predominantly recessive s effect for early-onset depression. 30,40,42 When multiple outcomes were considered within one sample, a co-dominant effect was shown for the more common outcome of alcohol abuse, but a recessive s effect was apparent for the less common illicit drug use.…”

Section: Allelic Variants Of 5-httlpr: L a And L G Or Rs25531mentioning

confidence: 99%

“…Taken at face value, there were eleven replications, 15,[29][30][31][32][33][34][35][36][37][38][39] three partial replications in females only, [40][41][42] and three non-replications. [43][44][45] Importantly, two studies with very large samples were negative.…”

Section: Human Studiesmentioning

confidence: 99%

“…The studies of G Â E in depression used stressful life events, 11,15,29,32,33,35,43,44 childhood abuse, 11,31,45,34 chronic somatic illness 41 and composite indexes of environmental adversity. 40,42 Moffitt et al 3 specified that a candidate environmental pathogen for G Â E should be a plausible cause of the disorder, proximal to the disorder onset, and have variable effect on different individuals; they further stipulated that cumulative, repeated, or protracted exposures are stronger pathogens than discrete acute events.…”

Section: Environmental Adversity and Stressorsmentioning

confidence: 99%

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The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Allelic Variants Of 5-httlpr: L a And L G Or Rs25531mentioning

confidence: 99%

Section: Human Studiesmentioning

confidence: 99%

Section: Environmental Adversity and Stressorsmentioning

confidence: 99%

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The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited

Karg¹,

Burmeister²,

Shedden³

et al. 2011

Arch Gen Psychiatry

1,265

1,090

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Context The initial report of an interaction between a serotonin transporter promoter polymorphism (5-HTTLPR) and stress in the development of depression is perhaps the best-known and most cited finding in psychiatric genetics. Two recent meta-analyses explored the studies seeking to replicate this initial report and concluded that the evidence did not support the presence of the interaction. However, even the larger of the meta-analyses included only 14 of the 56 studies that have explored the relationship between 5-HTTLPR, stress and depression. Objective We sought to perform a meta-analysis including all relevant studies assessing whether 5-HTTLPR moderates the relationship between stress and depression. Data Sources We identified relevant articles from previous meta-analyses and reviews and a PubMed database search. Study Selection We excluded two studies presenting data that were included in other, larger, studies already included in our meta-analysis to avoid duplicate counting of subjects. Data Extraction In order to perform a more inclusive meta-analysis, we used the Liptak-Stouffer Z-score method to combine findings of primary studies at the significance test level rather than raw data level. Results We included 54 studies and found strong evidence that 5-HTTLPR moderates the relationship between stress and depression, with the 5-HTTLPR s allele associated with an increased risk of developing depression under stress (p<0.0001). When restricting our analysis to the studies included in the previous meta-analyses, we found no evidence of association (Munafo studies p=0.16; Risch studies p=0.11). This suggests that the difference in results between previous meta-analyses and ours was not due to the difference in meta-analytic technique but instead to the expanded set of studies included in this analysis. Conclusions Contrary to the results of the smaller earlier meta-analyses, we find strong evidence that 5-HTTLPR moderates the relationship between stress and depression in the studies published to date.

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A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship

Sen¹,

Kranzler²,

Krystal³

et al. 2010

Arch Gen Psychiatry

318

323

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Context Although the prevalence of depression among medical interns substantially exceeds that of the general population, the specific factors responsible are not well understood. Recent reports of a moderating effect of a genetic polymorphism (5-HTTLPR) in the serotonin transporter protein gene on the likelihood that life stress will precipitate depression may help to understand the development of mood symptoms in medical interns. Objective To identify psychological, demographic and residency program factors that associate with depression among interns and use medical internship as a model to study the moderating effects of this polymorphism using a prospective, within-subject design that addresses the design limitations of earlier studies. Design Prospective cohort study Setting 13 United States hospitals Participants 740 interns entering participating residency programs Main outcome measures Subjects were assessed for depressive symptoms using the Patient Health Questionnaire (PHQ-9), a series of psychological traits and 5-HTTLPR genotype prior to internship and then assessed for depressive symptoms and potential stressors at 3-month intervals during internship. Results The PHQ-9 depression score increased from 2.4 prior to internship to a mean of 6.4 during internship (p<0.001). The proportion of participants who met PHQ-9 criteria for depression increased from 3.9% prior to internship to a mean of 25.7% during internship (p<0.001). A series of factors measured prior to internship (female sex, U.S. medical education, difficult early family environment, history of major depression, lower baseline depressive symptom score and higher neuroticism) and during internship (increased work hours, perceived medical errors and stressful life events) were associated with a greater increase in depressive symptoms during internship. In addition, subjects with at least one copy of a less transcribed 5-HTTLPR allele reported a greater increase in depressive symptoms under the stress of internship (p=0.002). Conclusions There is a marked increase in depressive symptoms during medical internship. Specific individual, internship and genetic factors are associated with the increase in depressive symptoms.

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Early Family Environment, Current Adversity, the Serotonin Transporter Promoter Polymorphism, and Depressive Symptomatology

Cited by 393 publications

References 22 publications

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

The Serotonin Transporter Promoter Variant (5-HTTLPR), Stress, and Depression Meta-analysis Revisited

A Prospective Cohort Study Investigating Factors Associated With Depression During Medical Internship

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