The DOI matches its Crossref record; 172 of the 174 references it cites were found in a registry or an index; 1 of the 97 sources its claims cite were checked for support.
Gene–environment interactions: early life stress and risk for depressive and anxiety disorders
Open accessAbstract
Rationale Prior reviews have examined how stress, broadly defined, interacts with genetic diathesis in the pathogenesis of internalizing (i.e., depressive and anxiety) disorders. Recent findings have suggested a unique role for early life stress (ELS) in the development of internalizing disorders, contributing to the rapid proliferation of research in this area.Objective This paper critically reviews studies in humans examining gene-environment interaction (GxE) effects of ELS on the risk for depression and anxiety, primarily from a candidate gene perspective. Major methodological challenges that are unique to such studies are considered.Results The majority of published studies have focused on candidates that regulate the serotonin system, especially the serotonin transporter. More recent work has addressed interactions of ELS with candidates from the hypothalamic-pituitary-adrenal axis and neurotrophin system. Available studies vary greatly with respect to definitions of ELS, examination of gene-gene interactions, consideration of gender effects, and attention to analytic limitations.Conclusions Overall, there is support for GxE effects of ELS on the risk for depressive and anxiety outcomes. Future studies of ELS in this context will require careful attention to methodologic considerations. Such studies would benefit from more systematic assessment of positive environmental factors (e.g., social support) and greater utilization of developmentally sensitive paradigms.
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70 Not checked yet · 10 No basis given · 9 Own interpretation · 3 Own method · 2 Own result · 1 Partly supported · accuracy not yet measured
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In the paper
“Findings from 15 of the 22 samples tested support increased risk for internalizing symptoms in participants with the low-expression short alleles and ELS in all participants”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
plaincorrelationaln = 15- Asserted: passes — The authors put it forward as true.
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In the paper
“many studies do not report whether they have tested for rGE between ELS and genotype”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
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In the paper
“the majority of G×ELS studies to date have involved gene variants that regulate brain serotonin systems (Tables 1 and 2); in particular, numerous studies have focused on 5-HTTLPR”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Another major source of inconsistency involves the type of early stress under study. Whereas some studies have focused on direct childhood maltreatment, such as abuse and neglect, others have included more broadly experienced events, such as parental arguing/divorce, or qualitatively distinct circumstances, such as poverty or parent education levels.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“However, relatively few studies separately test for GxE effects within gender or type of ELS.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Although no published meta-analyses have focused on gene by ELS interactions”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“published studies are characterized by considerable differences in methodology, especially in terms of ELS measurement.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
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In the paper
“Studies yielding inconsistent findings have often relied on suboptimal timing of ELS assessment (ranging from a single measurement at 3 months of age to retrospective accounts of childhood provided by advanced-age participants).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
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In the paper
“A substantially elevated risk of internalizing (i.e., depressive and anxiety) disorders following ELS is particularly well documented”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Early life stress and risk for depressive and anxiety disorders
What the sources say
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In the paper
“Early life stress (ELS) is an established predictor of adverse outcomes across the lifespan encompassing neurocognitive, behavioral, health, and psychiatric domains”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Early life stress and risk for depressive and anxiety disorders
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Polanczyk et al. concluded that the GxE effect was supported, but with the effect specific to depression-relevant emotional memories assessed with the CTQ.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Partly supportedcites Polanczyk et al. (2009) sourceExperimental — accuracy not yet measured
The Comment reports a significant gene–environment interaction in the E-Risk Study, where maltreatment was assessed with the CTQ, but no replication in the Dunedin Study. It describes the CTQ as tapping depression-relevant emotional memories; however, the authors present the role of those memories as a hypothesis they could not test, not an established specificity of the effect. Our copy provides no page numbers for these passages. (LLM, conf=0.89)
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- Partly supported
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In the paper
“most of the studies reviewed here have either comprised racially homogeneous groups or have adjusted their models for population stratification; however, some studies have not reported on this important issue”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“to our knowledge there is only 1 report examining interactions with ELS.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Other candidate genes
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, it is important to note that these reviews included studies of life events occurring throughout the lifespan and did not formally address the potentially differential effects of ELS relative to adult stressors.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Evidence from studies reviewed here supports the existence of differences in the impact of type of ELS, and these effects may be gender-specific (Cicchetti et al. 2007; Heim et al. 2009; Sjoberg et al. 2006).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Several studies have notably failed to detect these effects.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Conclusions and future directions
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Studies that did observe rGE should be interpreted with caution, as it is possible that rGE can account for apparent GxE effects.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In the first of two samples tested by Chipman et al. (2007), genotype frequencies were not in HWE, and no GxE interaction was detected.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
What the sources say
- Not checked yetcites Chipman et al. (2007) source
plainn = 2- Asserted: passes — The authors put it forward as true.
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In the paper
“Achieving sufficient statistical power presents a special challenge because interaction effects require larger numbers of subjects for adequate power (Brookes et al. 2001; Luan et al. 2001; Uher 2008), and power depends on allele frequencies in addition to exposure to ELS (Munafo et al. 2009).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, Aguilera et al. (2009) showed a GxE effect of the 5-HTTLPR s allele and a history of childhood sexual abuse on depressive symptoms, but also observed rGE, in which the l/l genotype was more strongly associated with childhood sexual abuse than the l/s genotype.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
What the sources say
- Not checked yetcites Aguilera et al. (2009) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Although no main or interaction effects for the 5-HT2C VNTR were found, a significant main effect for increased depression in T allele carriers of the 5-HT2A T102C was observed.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
What the sources say
- Not checked yetcites Eley et al. (2004) source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“In the case of ELS, the nature and timing of the stress exposure may be a critical determinant of the sequelae, while the method of assessment (i.e., prospective, retrospective; interview, records, questionnaire) may be similarly critical in permitting detection of any moderation by candidate risk genes”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In addition, there was a GxE interaction such that men reporting ELS with an A allele had decreased cortisol responses compared with women reporting ELS, but responses of men and women without ELS did not differ.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Not checked yetcites Heim et al. (2009) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“The short (s) allele of this polymorphism confers lower transcriptional efficiency than the long (l) allele, and is associated with decreased transporter expression and serotonin reuptake”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
What the sources say
- Not checked yetcites Lesch et al. 1996 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Wichers et al. (2008), identified a three-way interaction between ELS, 5-HTTLPR, and BDNF, which the authors acknowledged must be qualified by the fact that they also found rGE between BDNF genotype and reported childhood adversity (with increased adversity reported by youth with Val/Met relative to Val/Val).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
What the sources say
- Not checked yetcites Wichers et al. (2008) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Seven of ten single nucleotide polymorphisms (SNPs) spanning the gene showed significant interactions, with the rs110402 and rs7209436 SNPs significant even after correction for multiple tests.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Not checked yetcites Bradley et al. 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, continuous measures of depression or anxiety disorders are also problematic in that they generally provide accurate assessments only of current symptoms, and therefore may miscategorize those individuals who have a history of such symptoms but are currently in remission.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The effects of genetic and environmental factors on symptoms of depression and anxiety have also been shown to differ as a function of age (Tambs and Mourn 1993) and gender (Eaves et al. 1997), so these factors should be considered in GxE analyses.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Men, but not women, who were carriers of the A allele had decreased cortisol responses compared with men with the G/G genotype.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Not checked yetcites Heim et al. (2009) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“suggesting that prior findings of elevated depressive symptoms in individuals with this genotype and childhood maltreatment could reflect alterations in neuroendocrine stress responding.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Not checked yetcites Tyrka et al. (2009) source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“Although the replication sample did not show a departure from HWE, as the authors noted, findings from the replication sample were limited by the fact that very few adolescents categorized as having persistent adversity had high levels of depressive symptoms.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
What the sources say
- Not checked yetcites Chipman et al. (2007) source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Differences in both genetic and environmental determinants of childhood- vs. adult-onset disorders could be expected, limiting the validity of studies that combine these conditions.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Munafo et al. (2009) conducted a meta-analysis which led them to conclude that most of the available studies were underpowered, and that findings using logistic regression models were “compatible with chance.””
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
What the sources say
- Not checked yetcites Munafo et al. (2009) source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Reciprocal interactions between BDNF and serotonin have also been well documented (Duman 2002; MacQueen et al. 2003).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Neurotrophins
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“This effect was specific to depression and did not predict anxiety symptoms.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Other candidate genes
What the sources say
- Not checked yetcites Haeffel et al. 2008 source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Psychiatric disorders tend to co-occur, and are also heterogeneous, so that efforts to examine dichotomous diagnoses, a common approach in genetic research, are problematic (Eaves 2006).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
What the sources say
- Not checked yetcites Eaves 2006 source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Caspi et al. (2010), recently reviewing the role of 5-HTTLPR in stress sensitivity from a broader perspective, asserted a prominent role for this gene in the neurobiological and behavioral responses to stress.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
What the sources say
- Not checked yetcites Caspi et al. (2010) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Since altered sensitivity of GRs is thought to mediate HPA axis dysregulation in depression and PTSD (Raison and Miller 2003), genes regulating components of this system are likely candidates for GxE investigations of the etiopathology of depression and anxiety (Charney 2004; Wust et al. 2004a; Wust et al. 2004b).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Dopamine, which plays a central role in motivation and pleasure, has also been implicated in the pathophysiology of depression (Dunlop and Nemeroff 2007).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Other candidate genes
What the sources say
- Not checked yetcites Dunlop and Nemeroff 2007 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“and has been implicated in impaired extinction of conditioned fear response and atypical frontoamygdala activity in humans (Soliman et al. 2010)”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Neurotrophins
What the sources say
- Not checked yetcites Soliman et al. 2010 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“FKBP5 interacted with reported childhood maltreatment to predict PTSD symptoms.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Not checked yetcites Binder et al. 2008 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Examination of continuous measures affords greater statistical power and may decrease statistical error due to miscategorization of “subthreshold” individuals (Caspi et al. 2010; Plomin and Davis 2009).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
In the paper
“Significant interactions between BDNF Val66Met and ELS were observed, with BDNF Met carriers exposed to high ELS showing poorer working memory, elevated heart rate in resting and arousal conditions, and smaller hippocampus and amygdala volumes.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Neurotrophins
What the sources say
- Not checked yetcites Gatt et al. (2009) source
plaincorrelationaln = 374- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“a recent meta-analysis by Risch et al. (2009) examined GxE between stressful life events and 5-HTTLPR on depression using 14 studies (N=14,250). Just under half of the included studies focused on the effects of ELS. The authors concluded that there was no support for an interaction effect”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
What the sources say
- Not checked yetcites Risch et al. (2009) source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“there was an interaction between childhood experiences of crime and abuse and FKBP5 genotype in predicting PTSD in African Americans, but not European Americans.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > HPA axis
What the sources say
- Not checked yetcites Xie et al. (2009) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“studies reviewed here suggest that differences in findings may be attributable to: (1) type of ELS, (2) gender-related effects, (3) additional interactive or additive environmental influences, such as social support, and (4) additional moderating genes.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Conclusions and future directions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Timing of ELS is likely also critically important, and may further explain inconsistencies in the literature.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Conclusions and future directions
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The authors state this as an assumption.
Common diseases are influenced by common genetic variants.
“Candidate gene research is predicated on the assumption that common diseases are influenced by common genetic variants”
The paper relies on this without support.
Early life stress does not invariably lead to dysfunction and is not a specific risk factor for any particular disorder.
“ELS does not invariably lead to dysfunction, nor is it a specific risk factor for any particular disorder.”
The authors state this as an assumption.
An increasingly accepted gene–environment model assumes that genes may interact with environmental influences on both ends of the spectrum, with risk and resilience resulting from exposure to negative and positive environments, respectively.
“Finally, an increasingly accepted GxE model assumes genes may interact with environmental influences on both ends of the spectrum, with risk and resilience resulting from exposure to negative and positive environments, respectively.”
The paper relies on this without support.
Some types of adversity commonly co-occur, while others, such as sexual abuse, may occur in isolation.
“A further complication is that some types of adversity commonly co-occur, while others, such as sexual abuse, may occur in isolation.”
The paper relies on this without support.
Identified stressors may occur in the context of additional adversity that is not consistently identified or examined.
“Moreover, identified stressors may occur in the context of additional adversity that is not consistently identified or examined.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Candidate genetic risk factors play functional roles in serotonin transport, activation of the HPA-axis via corticotropin releasing hormone (CRH), glucocorticoid sensitivity, and production of brain derived neurotrophic factors (BDNF).”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Nugent et al., 2011
In the citing paper
“there is evidence to support that specific genetic risk factors can predispose an individual to psychopathology in the presence of increasing life stress”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Nugent et al., 2011
In the citing paper
“It is notable that each of these identified risk factors has distinct links to functioning of the HPA-axis and inflammatory activity.”
From Developmental psychoneuroendocrine and psychoneuroimmune pathways from childhood adversity to disease (2017) · cites this paper as Nugent et al., 2011
Citations
Cites
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120 · cited 14×
“Of the 13 studies including physical abuse as an ELS, ten found support for GxE with risk associated with the s/s′ allele (Aguilera et al. 2009; Åslund et al. 2009; Caspi et al. 2003; Cicchetti et al. 2007; Kaufman et al. 2006; Kaufman et al. 2004; Stein et al. 2008; Taylor et al. 2006; Wichers et al. 2008; Xie et al.…”
BackgroundMethodInfluentialLesch, K.-P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., Petri, S., Benjamin, J., Müller, C. R., Hamer, D. H., & Murphy, D. L. (1996) · Science · doi:10.1126/science.274.5292.1527 · Cited by 5,162 · cited 1×
“The short (s) allele of this polymorphism confers lower transcriptional efficiency than the long (l) allele, and is associated with decreased transporter expression and serotonin reuptake (Lesch et al. 1996).”
BackgroundStress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621 · cited 1×
“Converging findings from preclinical and clinical studies indicate that exposure to excessive glucocorticoid concentrations impedes neuroprotection and neurogenesis in the hippocampus, effects linked to the pathogenesis of depression and anxiety disorders (De Kloet et al. 2005).”
BackgroundMethodology for Genetic Studies of Twins and Families
Neale, M. C., & Cardon, L. R. (1992) · doi:10.1007/978-94-015-8018-2 · Cited by 4,005
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., Zaitsev, E., Gold, B., Goldman, D., Dean, M., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00035-7 · Cited by 3,888 · cited 2×
“The Met allele of the functional BDNF Val66Met polymorphism confers abnormal intracellular packaging and secretion of BDNF (Egan et al. 2003), and has been implicated in impaired extinction of conditioned fear response and atypical frontoamygdala activity in humans (Soliman et al. 2010), as well as…”
BackgroundA Neurotrophic Model for Stress-Related Mood Disorders
Duman, R. S., & Monteggia, L. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.013 · Cited by 3,375 · cited 20×
“A study of depressed inpatients found that those with two copies of the Met allele of BDNF Val66Met had elevated adrenocorticotropic hormone and cortisol responses to the Dex/CRH text (Schule et al. 2006).”
BackgroundInfluentialBeyond diathesis stress: differential susceptibility to environmental influences
Belsky, J., & Pluess, M. (2009) · Psychological Bulletin · doi:10.1037/a0017376 · Cited by 3,039 · cited 2×
“It is also possible for certain genes to confer environmentally sensitive “plasticity” such that the same genetic variant may confer risk under harmful environmental circumstances but provide benefit under auspicious conditions (Belsky et al. 2009; Belsky and Pluess 2009; Fox et al. 2007).”
BackgroundNature-nurture reconceptualized in developmental perspective: A bioecological model.
Bronfenbrenner, U., & Ceci, S. J. (1994) · Psychological Review · doi:10.1037/0033-295x.101.4.568 · Cited by 2,973 · cited 3×
“Consistent with early theory (Bronfenbrenner and Ceci 1994), twin models of both internalizing and externalizing have suggested that socioeconomically disadvantaged environments may obscure genetic effects (Raine 2002; South and Krueger 2010; Tuvblad et al.”
BackgroundValidity of adult retrospective reports of adverse childhood experiences: review of the evidence
Hardt, J., & Rutter, M. (2004) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2004.00218.x · Cited by 2,827 · cited 2×
“…may be a critical determinant of the sequelae, while the method of assessment (i.e., prospective, retrospective; interview, records, questionnaire) may be similarly critical in permitting detection of any moderation by candidate risk genes (Hardt and Rutter 2004; Moffitt et al. 2005; Paivio 2001).”
BackgroundMethodChristakis, D., Richards, J. A., Zimmerman, F. J., Garrison, M. M., Xu, D., & Yapanel, U. H. (2009) · Cited by 2,290
Cited by
Sorted by citations
Snyder, H. R. (2013) · Psychological Bulletin · doi:10.1037/a0028727 · Cited by 1,667
Child Development in the Context of Disaster, War, and Terrorism: Pathways of Risk and Resilience
Masten, A. S., & Narayan, A. J. (2011) · Annual Review of Psychology · doi:10.1146/annurev-psych-120710-100356 · Cited by 1,173
“…in stress response, also have been implicated as potential moderators of trauma response in geneby-environment (G x E) studies, including research on the corticotropin-releasing hormone type 1 receptor and glucocorticoid receptor genes (Cicchetti 2010, Nugent et al. 2011, Pratchett & Yehuda 2011).”
de Figueiredo, C. S., Sandre, P. C., Portugal, L. C. L., Mázala-de-Oliveira, T., Chagas, L. D. S., Raony, Í., Ferreira, E. S., Giestal‐de‐Araujo, E., dos Santos, A. A., & Oliveira-Silva, P. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110171 · Cited by 720
Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure
van Bodegom, M., Homberg, J. R., & Henckens, M. J. A. G. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00087 · Cited by 606
Cultural evolutionary theory: How culture evolves and why it matters
Creanza, N., Kolodny, O., & Feldman, M. W. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1620732114 · Cited by 482
Metadata
- Authors
- Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H.
- Affiliations
- Brown University (US)
- Corresponding author
- Nugent, Nicole R.
- Venue
- Psychopharmacology
- Published
- 2011-01-12
- Volume
- 214
- Issue
- 1
- Pages
- 175-196
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC3615637
- OpenAlex
- W2094951488
- Cited by
- 269
- References
- 174
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 8 · 2023: 16 · 2022: 40 · 2021: 14 · 2020: 13 · 2019: 11 · 2018: 17 · 2017: 25 · 2016: 10 · 2015: 30 · 2014: 20 · 2013: 25 · 2012: 17
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- National Institute of Mental Health (K01MH087240, R01MH083704, R01MH068767)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Keywords
- gene-environment interaction, early life stress, depression, anxiety disorders, internalizing disorders, candidate genes, serotonin transporter, serotonergic system, hypothalamic-pituitary-adrenal axis, neurotrophins, gene-gene interaction, sex differences, social support
- MeSH terms
- Animals, Anxiety Disorders, Depressive Disorder, Female, Humans, Life Change Events, Male, Risk Factors, Sex Factors, Stress, Psychological
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