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
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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
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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
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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
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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
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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
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In the paper
“Such divergent outcomes can be explained in part by gene-environment (GxE) interactions, in which genetic differences influence the likelihood that exposure to ELS will result in psychopathology.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions
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- Rests on an assumption: Early life stress does not invariably lead to dysfunction and is not a specific risk factor for any particular disorder.
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In the paper
“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”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions
What the sources say
- Not checked yetcites Belsky et al. 2009
- Not checked yetcites Belsky and Pluess 2009
- Not checked yetcites Fox et al. 2007 source
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In the paper
“It is important that the study sample contains adequate numbers of subjects exposed and unexposed to the stressful environment to ensure adequate power”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
What the sources say
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In the paper
“For both polymorphisms, individuals with the G/G genotype and reported childhood maltreatment had an elevated cortisol response”
§ 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
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In the paper
“Nobile et al. (2009) examined the effects of being in a single-parent family during childhood/adolescence, with a significant GxE identified with TPH2 such that allele 5 decreased the risk of high depressive symptoms in single-parent youth.”
§ 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 Nobile et al. (2009) source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“ELS analyses also showed a significant GxE interaction, with the s allele of this gene predicting the subsequent development of major depression among those with ELS.”
§ 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 Caspi et al. 2003 source
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In the paper
“Extensive research supports a role for the serotonin system in the development of both mood and anxiety disorders”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Selecting candidate genes
What the sources say
- Not checked yetcites Ressler and Nemeroff 2000 source
boostedcorrelational- 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
“The validity of studies that do not supplement parent report with additional sources of information may be limited by the fact that parents may not be aware of all of their childs stressors.”
§ 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
“Findings from their E-Risk cohort, a large study of women, replicated the interaction of retrospective reports of childhood maltreatment with the TAT haplotype (rs7209436, rs110402, and rs242924) in predicting depression diagnoses.”
§ 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 Polanczyk et al. (2009) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“One proposed mechanism of ELS interactions with serotonergic genes such as 5-HTTLPR involves modulation of stress responses through HPA axis activity (El Hage et al. 2009).”
§ 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 El Hage et al. 2009 source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The use of logistic regression techniques to identify interactions in GxE studies is widespread, but it is important to note that this technique can lead to both false-positive and false-negative findings”
§ 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
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“there is extensive evidence documenting perturbed HPA function both as a result of ELS and in the context of depression and certain anxiety disorders (particularly PTSD)”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Selecting candidate genes
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Yet another concern when testing for interaction effects is the potential for artifactual interactions that can occur secondary to subtle changes in definition and scaling of the variables”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Another important consideration is that individuals may shape their environments or elicit certain types of responses or stimuli in their environment, resulting in gene–environment correlation (rGE)”
§ 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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In the paper
“No significant main effects or interactions were found in the prediction of depression or anxiety 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. (2010) source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Using an independent sample, these authors also examined the interaction between CRHR1 rs110402 and ELS in predicting depression, again finding an interaction of ELS (particularly physical abuse) and CRHR1 in men only.”
§ 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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In the paper
“Bradley et al. found an interaction between reports of childhood maltreatment on the Childhood Trauma Questionnaire (CTQ) and CRHR1 in predicting depressive symptoms in a sample of predominantly African-American and low socioeconomic status adults (Bradley et al. 2008).”
§ 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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In the paper
“Findings revealed a significant protective effect of TPH1 on depressive symptoms in relation to ELS, which consisted of family problems, parent education, and adverse events occurring in adolescence.”
§ 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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In the paper
“Participants with a history of childhood maltreatment who had the G/G rs110402 genotype had the highest depressive 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 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
“Population stratification, or variation in allele frequency as a function of race/ancestry, is another major consideration, because if a mixed-ethnicity sample is used without control for population stratification, spurious GxE effects can result.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Methodological considerations
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Brain-derived neurotrophic factor (BDNF), a nerve growth factor that supports neuronal survival and plasticity, has recently been strongly implicated in the pathophysiology of major depression”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Gene–environment interactions > Selecting candidate genes
What the sources say
- Not checked yetcites Duman and Monteggia 2006 source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In a replication sample, predominantly Caucasian and of higher socioeconomic status, the authors further examined common haplotypes of CRHR1, detecting a GxE protective effect on depression in individuals with a history of childhood maltreatment who possessed a TAT haplotype formed by three CRHR1 variants (rs7209436, rs110402, and rs242924).”
§ 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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In the paper
“However, results from the Dunedin cohort, comprised of both men and women, did not support the expected GxE interaction.”
§ 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 Polanczyk et al. (2009) source
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
“Divergence from HWE in GxE studies can arise from a number of sources, ranging from population stratification characteristics, to genotyping error, to aspects of sampling.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Candidate genes and effects of early life stress > Serotonin system
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The Met allele of the functional BDNF Val66Met polymorphism confers abnormal intracellular packaging and secretion of BDNF (Egan 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
- Not checked yetcites Egan et al. 2003 source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Research supports differences in neurobiological and treatment-response characteristics of depression with onset in childhood, adolescence, and adulthood (Rutter 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
- Not checked yetcites Rutter et al. 2006 source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In a path analysis, reduced gray matter in the hippocampus and lateral prefrontal cortex mediated the impact of the GxE interaction in predicting depressive symptoms.”
§ 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
plaindirectn = 89- Asserted: passes — The authors put it forward as true.
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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
“If a particular form of adversity, such as childhood sexual abuse, is the critical environmental component, failure to adequately detect this could result in its unrecognized presence in both ELS and control groups.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: Some types of adversity commonly co-occur, while others, such as sexual abuse, may occur in isolation.
- Rests on an assumption: Identified stressors may occur in the context of additional adversity that is not consistently identified or examined.
In the paper
“In a study of 176 male juvenile detainees, the dopamine transporter gene (DAT1) interacted with reported maternal rejection in predicting both depression and suicidal ideation (Haeffel et al. 2008).”
§ 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
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, these interaction effects remained significant even after controlling for potential confounds (i.e., depressive symptoms, age, sex, non-child abuse trauma, genetic ancestry).”
§ 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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In the paper
“Similarly, startle-elicited heart rate mediated the effects of BDNF×ELS on neuroticism, which predicted increased depressive and anxiety symptoms.”
§ 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
plaindirectn = 374- Asserted: passes — The authors put it forward as true.
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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
“Consideration of the timing of onset and chronicity of illness may also influence findings of GxE investigations.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Inconsistencies in the literature: methodological issues
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The 22/23 K and 9beta polymorphisms interacted with childhood adversity to predict depressive 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 Bet et al. (2009) source
plaincorrelationaln = 906- 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
“As discussed above, the studies by Kaufman et al. (2006) and Wichers et al. (2008) demonstrate that BDNF Val66Met acts as a moderator of 5-HTTLPR×ELS interactions.”
§ 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.
- 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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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
“In spite of significant variability in methodology and findings, taken together these studies provide support for GxE effects of genes in the serotonin, HPA axis, and neurotrophin systems in predicting depressive and anxiety disorders.”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Conclusions and future directions
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Moreover, the 22/23EK variant was associated with a lower morning free cortisol index in subjects reporting childhood adversity.”
§ 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 Bet et al. (2009) source
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Consistent with this, the s′ allele of 5-HTTLPR has been associated with an exaggerated cortisol response to a standardized psychosocial stressor in children and adults (Alexander et al. 2009; Gotlib et al. 2008).”
§ 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
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.
In the paper
“In a subsequent systematic review, the 14 studies (out of 34 possible studies) included in the Risch report were found to show a statistically significant bias toward negative findings (Uher and McGuffin 2010).”
§ 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 Uher and McGuffin 2010 source
plain- 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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Also in subjects reporting childhood adversity, heterozygotes for the Bcl1 variant had lower serum cortisol binding globulin and less risk of depressive symptoms than either wild type or Bcl1 homozygous subjects.”
§ 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 Bet 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.
In the paper
“Aguilera et al. (2009) found that carriers of the Met allele of the BDNF Val66Met polymorphism with reported childhood abuse had greater risk for depressive symptoms than abused participants with the Val/Val genotype.”
§ 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 Aguilera 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.
In the paper
“and there is evidence that the ELS profiles of individuals with childhood- vs. adult-onset depression differ (Jaffee et al. 2002).”
§ 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 Jaffee et al. 2002 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.
In the paper
“The s′ allele of 5-HTTLPR enhanced the effects of the CRHR1 risk haplotype, even under conditions of lower levels of abuse.”
§ 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 Ressler et al. (2010) source
plaindirect- 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.
In the paper
“Significant interactions were observed between ELS and three of the four GABRA2 SNPs in predicting lifetime risk for PTSD.”
§ 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 Nelson et al. 2009 source
plaincorrelationaln = 259- 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.
- Based: passes — The paper gives a reason why it holds.
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
“ELS is difficult to assess, reflecting the subjectivity inherent to the experience of stress, biases involved in reporting and recall, and the developmental context in which such experiences occur.”
§ 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.
- 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.
In the paper
“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).”
§ 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 Schule et al. 2006 source
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“as well as reduced amygdala and hippocampus volume (Montag et al. 2009).”
§ 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 Montag et al. 2009 source
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In contrast, a specificity path analysis did not show similar effects with the 5-HTTLPR gene.”
§ 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
plain- 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.
- Based: passes — The paper gives a reason why it holds.
In the paper
“emerging epigenetic research suggests that timing of stress may be linked to functional alterations of genes implicated in depression (Murgatroyd et al. 2010).”
§ Gene–environment interactions: early life stress and risk for depressive and anxiety disorders > Conclusions and future directions
What the sources say
- Not checked yetcites Murgatroyd et al. 2010 source
hedgedcorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 30
- Probably not a substantial claim. 8
- The quote only partly states this claim. 1
The cited sources support only part of this claim — read each source’s verdict below.
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)
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.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
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 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.
- 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
None of the sources cited for this claim have been checked yet.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
None of the sources cited for this claim have been checked yet.
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.
- 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
“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.
- 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
“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.
- 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
“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.
- 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
“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.
- 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.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- 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
“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.
- 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.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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
“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.
- 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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
“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.
- 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- 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
“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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
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.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether 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
“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.
- 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.
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.
- Based: passes — The paper gives a reason why it holds.
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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