Brain-Derived Neurotrophic Factor–5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children

Kaufman, Joan; Yang, Bao Zhu; Douglas‐Palumberi, Heather; Grasso, Damion J.; Lipschitz, Deborah S.; Houshyar, Shadi; Krystal, John H.; Gelernter, Joel

doi:10.1016/j.biopsych.2005.10.026

Cited by 653 publications

(602 citation statements)

References 57 publications

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“…The one study in children shows interaction effect consistent with the young adult studies. 31 The two adolescent studies both show an interaction in the expected direction among females only and trend for an opposite effect in males. 40,42 The G Â E interaction is consistently positive in young adults.…”

Section: Methodsmentioning

confidence: 94%

“…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%

“…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%

See 3 more Smart Citations

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: 94%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Human Studiesmentioning

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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“…Further support for the aforementioned is reflected in findings of gene x gene and gene x gene x environment interactions which are indicative of significant interaction effects of the BDNF Val66Met polymorphism and the serotonin transporter gene ( SLC6A4 ) on anxiety-related traits (e.g. neuroticism and harm avoidance) (Arias et al, 2012; Terracciano et al, 2010) and depressive symptoms and disorder (Gutiérrez et al, 2015; Kaufman et al, 2006). Finally, the effects of environmental influences other than CM, such as parenting rearing practices (Ibarra et al, 2014) and general self-efficacy (Schiele et al, 2016), on AS should be explored.…”

Section: Discussionmentioning

confidence: 99%

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample

Martin

Hemmings

Kidd

et al. 2018

European Journal of Psychotraumatology

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Background: Anxiety disorders in youth are attributable to multiple causal mechanisms, comprising biological vulnerabilities, such as genetics and temperament, and unfavourable environmental influences, such as childhood maltreatment (CM).Objective: A gene-environment (G x E) interaction study was conducted to determine the interactive effect of the BDNF Val66Met polymorphism and CM to increase susceptibility to anxiety sensitivity (AS) in a sample of mixed race adolescents.Method: Participants (n = 308, mean age = 15.8 years) who were all secondary school students and who completed measures for AS and CM were genotyped for the BDNF Val66Met polymorphism. Hierarchical multiple regression analysis was conducted to assess G x E influences on AS. Age and gender were included in the models as covariates as age was significantly associated with AS total score (p < .05), and females had significantly higher AS scores than males (p < .05).Results: A main effect of CM on AS was evident (p < .05), however, no main effect of BDNF genotype on AS was observed (p > .05). A non-significant G x E effect on AS was revealed (p < .05).Conclusions: Our results suggest that CM does not have a moderating role in the relationship between the BDNF Val66Met genotype and the increased risk of anxiety-related phenotypes, such as AS. Given the exploratory nature of this study, findings require replication in larger samples and adjustment for population stratification to further explore the role of BDNF Val66Met and CM on AS in mixed race adolescents.

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Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations

Xie¹,

Kranzler²,

Poling³

et al. 2009

Arch Gen Psychiatry

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222

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Context: The 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) has been found to moderate several categories of emotional response after stressful life events. Previous studies generally focused on its effect on depressive symptoms; little is known about its moderation of the development of post-traumatic stress disorder (PTSD). Objective: To examine the effects of childhood adversity, adult traumatic events, 5-HTTLPR genotypes, and gene×environment interactions on the etiology of PTSD. Design: A cross-sectional study in which participants in several studies investigating the genetics of substance dependence were also screened for lifetime PTSD. The triallelic system of 5-HTTLPR was genotyped. Logistic regression modeling was used in the analyses. Setting: General community. Participants: Five hundred eighty-two European American and 670 African American individuals who reported experiences of childhood adversity, adult traumatic events, or both. Main Outcome Measure: Diagnosis of PTSD, defined by DSM-IV diagnostic criteria and assessed through the Semi-Structured Assessment for Drug Dependence and Alcoholism interview. Results: Childhood adversity and adult traumatic events both predicted PTSD. Although the 5-HTTLPR genotype alone did not predict the onset of PTSD, it interacted with adult traumatic events and childhood adversity to increase the risk for PTSD, especially for those with high rates of both types of trauma exposure (European American: odds ratio [OR], 2.86; 95% confidence interval [CI], 1.50-5.45; P=.002; African American: OR, 1.88; 95% CI, 1.04-3.40; P=.04; pooled: OR, 2.31; 95% CI, 1.50-3.56; P<.001). Conclusions: Participants 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. The risk was increased in individuals with 1 or 2 copies of the S′ (S) allele compared with the L′ (L) homozygotes. Our study provides additional direct evidence that PTSD is influenced by the interactive effect of environmental and genetic factors.

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Brain-Derived Neurotrophic Factor–5-HTTLPR Gene Interactions and Environmental Modifiers of Depression in Children

Cited by 653 publications

References 57 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

No gene-by-environment interaction of BDNF Val66Met polymorphism and childhood maltreatment on anxiety sensitivity in a mixed race adolescent sample

Interactive Effect of Stressful Life Events and the Serotonin Transporter 5-HTTLPR Genotype on Posttraumatic Stress Disorder Diagnosis in 2 Independent Populations

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