The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index; 35 of the 60 sources its claims cite were checked for support.
Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation
Open accessAbstract
Background The involvement of epigenetic mechanisms in intergenerational transmission of stress effects has been demonstrated in animals but not in humans. Methods Cytosine methylation within the gene encoding for FK506 binding protein 5 (FKBP5) was measured in Holocaust survivors (n = 32), their adult offspring (n = 22), and demographically comparable parent (n = 8) and offspring (n = 9) control subjects, respectively. Cytosine-phosphate-guanine sites for analysis were chosen based on their spatial proximity to the intron 7 glucocorticoid response elements. Results Holocaust exposure had an effect on FKBP5 methylation that was observed in exposed parents as well in their offspring. These effects were observed at bin 3/site 6. Interestingly, in Holocaust survivors, methylation at this site was higher in comparison with control subjects, whereas in Holocaust offspring, methylation was lower. Methylation levels for exposed parents and their offspring were significantly correlated. In contrast to the findings at bin 3/site 6, offspring methylation at bin 2/sites 3 to 5 was associated with childhood physical and sexual abuse in interaction with an FKBP5 risk allele previously associated with vulnerability to psychological consequences of childhood adversity. The findings suggest the possibility of site specificity to environmental influences, as sites in bins 3 and 2 were differentially associated with parental trauma and the offspring's own childhood trauma, respectively. FKBP5…
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35 of 60 cited sources checked · 21 supported · 1 flagged · accuracy not yet measured
At least one cited source doesn’t support this claim or points to a different paper, and none confirmed it — see the verdicts below.
In the paper
“Furthermore, both bins within intron 7 appear to be equally sensitive to glucocorticoid-dependent FKBP5 demethylation in a multipotent human hippocampal progenitor cell line (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Disputedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci sourceExperimental — accuracy not yet measured
The Results report dexamethasone-induced demethylation in intron 7 of human hippocampal progenitor cells, but say the bin affected by early trauma showed the strongest demethylation—not that the bins were equally sensitive. The Methods also describe three CpG bins in intron 7, rather than two. (LLM, conf=0.82)
Checked by a reasoning model — may be wrong.
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“Second, reporter gene assays established that methylation of the sites affected FKBP5 gene expression (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci source
The Results section reports that a methylated FKBP5 intron 7 reporter construct had significantly lower dexamethasone-induced activity than an unmethylated construct. The effect was specific to glucocorticoid stimulation; methylation did not affect baseline activity. Page numbers are not available in our copy. (LLM, conf=0.91)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“After extensive investigation of all relevant regions in the FKBP5 gene that had GR-binding signals including the promoter regions and introns 2, 5, and 7 (31,39), Klengel et al. (38) demonstrated that only intron 7 CpG sites were differentially methylated in response to early abuse in the presence of FKBP5 rs1360780 risk allele.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci source
The Results report a significant childhood-abuse × rs1360780 genotype interaction on methylation in intron 7 bin 2, but not in the other tested CpG bins. The effect was a decrease in methylation among abuse-exposed risk-allele carriers; the finding concerns this specific bin, not every CpG in intron 7. (LLM, conf=0.92)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“since FKBP5 site-specific demethylation occurs with age (49).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Supportedcites [49] Blair, 2013, Accelerated neurodegeneration through chaperone-mediated oligomerization of tau, J Clin Invest source
Figure 7 (p. 8) reports significant age-related demethylation at specific FKBP5 CpG sites in intron 7 and the promoter. The research article text (p. 9) likewise reports decreased methylation with aging at seven sites in those regions. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Third, using a multipotent human hippocampal progenitor cell line, four of these sites (3 to 6) were shown to be demethylated by glucocorticoid administration (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Partly supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci sourceExperimental — accuracy not yet measured
The Results report that dexamethasone caused significant demethylation of FKBP5 intron 7 CpGs in a multipotent human hippocampal progenitor cell line. They identify three CpGs in the most strongly affected bin, but do not establish that four sites numbered 3–6 were demethylated. (LLM, conf=0.84)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“First, an experiment using chromatin conformation capture revealed that intron 7 is in direct physical contact with the FKBP5 transcriptional start site (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci source
The Results report that chromatin conformation capture found an interaction between FKBP5 intron 7 and the transcription start site through three-dimensional loop formation. The Methods describe the chromatin conformation capture experiment used to assess that interaction. (LLM, conf=0.94)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Klengel et al. (38) and other investigators (51,52) focusing on early childhood trauma effects and the influence of the gene 3 early life environment interactions on methylation did not assess the contribution of parental experiences, particularly trauma exposure.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci source
The Methods (Psychometric instruments; page unavailable) describe measures of participants’ own childhood and lifetime trauma. The Methods analysis of FKBP5 methylation includes participants’ trauma exposure and genotype, but no parental experiences or parental trauma exposure. This supports the claim as it applies to Klengel et al.; the other cited investigators are outside this verdict. (LLM, conf=0.87)
- Partly supportedcites [51] Turecki, 2016, Effects of the social environment and stress on glucocorticoid receptor gene methylation: A systematic review, Biol Psychiatry sourceExperimental — accuracy not yet measured
The Conclusion describes Klengel et al.’s finding on childhood maltreatment, FKBP5 genotype and methylation. The Results discuss parental stress in a separate group of studies, but do not establish that Klengel et al. or the other investigators named in the citing sentence failed to assess parental trauma exposure. (LLM, conf=0.78)
- Partly supportedcites [52] Daskalakis, 2014, Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: Systematic review of contributing factors, Front Neurosci sourceExperimental — accuracy not yet measured
The sections on GR-1F promoter site-specific methylation and possible transgenerational effects distinguish studies of childhood adversity from work assessing parental trauma or PTSD, and note that the two influences are difficult to disentangle (page unavailable). The review does not establish that Klengel et al. or all the other investigators cited failed to assess parental experiences, so that categorical part is unsupported. (LLM, conf=0.73)
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These results partially replicate previous findings (38) in which bin 2 demethylation was associated with physical and sexual abuse, the FKBP5 risk allele, and their interaction in two separate large cohorts.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Partly supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci sourceExperimental — accuracy not yet measured
The Results (page unavailable) report that intron 7 bin 2 methylation was associated with childhood abuse, FKBP5 risk genotype, and their interaction in the first cohort. In the second cohort, methylation correlated with physical abuse among risk-genotype carriers, but not with sexual abuse. The claim therefore overstates the findings across both cohorts; the methylation analyses involved 76 and 56 participants, respectively, rather than two large samples. (LLM, conf=0.88)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“alterations in methylation at bins 1, 2, and 3 affect GR-induced FKBP5 gene transcription as shown by reporter-gene assay (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Partly supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci sourceExperimental — accuracy not yet measured
The Results ('Functional effects of intron 7 demethylation'; page unavailable) report that methylating an intron 7 reporter construct reduced its dexamethasone-induced activity. The Methods identify bins 1, 2, and 3 in that region, but the assay methylated the construct as a whole; it did not show that alterations in each bin individually affect transcription. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Lower methylation leading to higher FKBP5 messenger RNA and protein levels has been linked to decreased GR sensitivity (38)”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Partly supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci sourceExperimental — accuracy not yet measured
The Results (page not available in our copy) link lower intron 7 methylation to greater glucocorticoid-induced FKBP5 expression and increased glucocorticoid receptor resistance. They do not establish that lower methylation raises FKBP5 protein levels, and report no association with baseline FKBP5 expression. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
- Probably not a substantial claim. 18
- It may state two separate claims as one. 20
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Enduring behavioral responses to stress and epigenetic alterations in adult offspring have been demonstrated to be mediated by changes in gametes (10)(11)(12)(13), in utero effects (14), variations in early postnatal care (15,16), and/or other early life experiences (17) that are influenced by parental exposure (18).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Abstract
What the sources say
- Supportedcites [10] Dias, 2014, Parental olfactory experience influences behavior and neural structure in subsequent generations, Nat Neurosci source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Not checked — no full text of the sourcecites [11] Zaidan, 2013, Prereproductive stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring, Biol Psychiatry source
- Supportedcites [12] Franklin, 2010, Epigenetic transmission of the impact of early stress across generations, Biol Psychiatry source
Citation 18 is attached to the claim that parental exposure influences outcomes in offspring, not to the separately cited list of mediating mechanisms. The Abstract reports that early stress in male mice was followed by behavioral alterations and DNA-methylation changes in their offspring; the Results say those offspring were raised under normal conditions. (LLM, conf=0.88)
- Supportedcites [13] Rodgers, 2013, Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation, J Neurosci source
The citation is attached to the point that parental exposure can influence offspring outcomes. The Introduction (page unavailable) says parental environmental exposures can shape offspring neurodevelopment and identifies changes in the intrauterine environment, lactation, and maternal behavior as relevant pathways. The paper does not need to establish every separately cited mechanism in the sentence to support this point. (LLM, conf=0.86)
- Supportedcites [14] Boersma, 2014, Prenatal stress decreases Bdnf expression and increases methylation of Bdnf exon IV in rats, Epigenetics source
Citation (14) is attached to the in utero effects, not to the separately cited gamete or postnatal-care pathways. The Experimental set-up and Abstract report gestational stress exposure followed by altered Bdnf expression and DNA methylation in adult rat offspring; the Introduction also describes lasting behavioral effects of prenatal stress. The paper does not itself measure offspring behavior, but it reports that evidence as background. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites [15] Champagne, 2006, Maternal care associated with methylation of the estrogen receptor-alpha1b promoter and estrogen receptor-alpha expression in the medial preoptic area of female offspring, Endocrinology source
- Not checked — no full text of the sourcecites [16] Weaver, 2004, Epigenetic programming by maternal behavior, Nat Neurosci source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Differential methylation of the glucocorticoid receptor (GR) gene associated with maternal behavior has been observed in F1 in rodents at Nr3c1 exon 1 7 promoter (16) and in human offspring with parental PTSD at the ortholog NR3C1 exon 1 F promoter (24).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Abstract
What the sources say
- Not checked — no full text of the sourcecites [16] Weaver, 2004, Epigenetic programming by maternal behavior, Nat Neurosci source
- Supportedcites [24] Yehuda, 2014, Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring, Am J Psychiatry source
The citation is attached to the human-offspring portion of the sentence. The Results (Maternal PTSD, Paternal PTSD and GR-1F promoter methylation) report differences in NR3C1 exon 1F promoter methylation associated with parental PTSD in offspring of Holocaust survivors; the Introduction identifies this human promoter as orthologous to the rat promoter. (LLM, conf=0.93)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Animal models have demonstrated that stress exposure can result in epigenetic alterations in the next generation, and such mechanisms have been hypothesized to underpin vulnerability to symptoms in offspring of trauma survivors (6)(7)(8)(9).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Abstract
What the sources say
- Not checked — no full text of the sourcecites [6] Gapp, 2014, Early life epigenetic programming and transmission of stress-induced traits in mammals: How and when can environmental factors influence traits and their transgenerational inheritance?, Bioessays source
- Partly supportedcites [7] Yehuda, 2009, The relevance of epigenetics to PTSD: Implications for the DSM-V, J Trauma Stress sourceExperimental — accuracy not yet measured
The section “Cytosine Methylation in Response to Variations in Maternal Care: A Behavioral Model” (page unavailable) reports altered DNA methylation in rat pups receiving different levels of maternal care and says associated biological effects were transmitted to a third generation. It does not clearly demonstrate that stress exposure in one generation caused epigenetic alterations in the next; the animal model described is one of variation in maternal care. (LLM, conf=0.82)
- Not checked — no full text of the sourcecites [8] Bale, 2015, Epigenetic and transgenerational reprogramming of brain development, Nat Rev Neurosci source
- Not checked — no full text of the sourcecites [9] Dias, 2015, Epigenetic mechanisms underlying learning and the inheritance of learned behaviors, Trends Neurosci source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
Every source the paper cites for this claim was checked and supports it.
In the paper
“For example, lower 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) activity was observed in Holocaust survivors compared with control subjects, presumably reflecting an enduring adaptive response to extreme nutritional deprivation (19).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Abstract
What the sources say
- Supportedcites [19] Yehuda, 2009, Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors, J Psychiatr Res source
The Results report a significantly elevated urinary F/E ratio in Holocaust survivors compared with controls, suggesting lower 11β-HSD-2 activity. The Discussion describes this change as potentially beneficial during starvation or salt depletion and associates it with starvation or other Holocaust-specific trauma, consistent with the claim’s hedged interpretation. (LLM, conf=0.91)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“FKBP5 effectively decreases glucocorticoid binding to GR, impeding GR translocation to the nucleus (29,30).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Not checked — no full text of the sourcecites [29] Pratt, 1997, Steroid receptor interactions with heat shock protein and immunophilin chaperones, Endocr Rev source
- Partly supportedcites [30] Wochnik, 2005, FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells, J Biol Chem sourceExperimental — accuracy not yet measured
The Discussion reports reduced hormone binding and demonstrates that FKBP51 delays GR nuclear translocation. But it describes impaired translocation as an additional effect: the 'FKBP51 Inhibits Nuclear Translocation of GR' section finds a delay even at saturating hormone concentrations, when the binding-affinity effect is excluded. The claim's implication that reduced binding causes the translocation delay is therefore too broad. (LLM, conf=0.83)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“Early abuse induced demethylation in the presence of the FKBP5 risk allele was demonstrated for three of the sites (3 to 5) in adult peripheral blood (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci source
The Results report that, in DNA from peripheral blood cells, three CpGs in FKBP5 intron 7 showed an average 12.3% decrease in methylation among childhood-abuse-exposed risk-allele carriers compared with the other groups. The Methods identify peripheral blood as the DNA source. (LLM, conf=0.91)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Epigenetic effects in maternal or paternal gametes are a potential explanation for epigenetic effects in offspring (10-13), but blood samples will not permit ascertainment of gamete-dependent transmission.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > DISCUSSION
What the sources say
- Supportedcites [10] Dias, 2014, Parental olfactory experience influences behavior and neural structure in subsequent generations, Nat Neurosci source
The Results section says the authors investigated sperm for epigenetic changes because their data suggested inheritance via parental gametes; they found reduced methylation at an olfactory-receptor locus in sperm from exposed fathers. This supports the cited proposition that gamete-based epigenetic effects are a potential explanation for effects in offspring. The statement about what blood samples can establish follows the citation and is not attributed to this source. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [11] Zaidan, 2013, Prereproductive stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring, Biol Psychiatry source
- Supportedcites [12] Franklin, 2010, Epigenetic transmission of the impact of early stress across generations, Biol Psychiatry source
The citation attaches to the proposed gamete-based explanation, not the subsequent statement about blood samples. The Results report altered DNA methylation in the male germline that may be passed to offspring, supporting a paternal-gamete mechanism; the paper need not establish a maternal mechanism to support this possibility. (LLM, conf=0.91)
- Supportedcites [13] Rodgers, 2013, Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation, J Neurosci source
The Introduction (page not provided) proposes epigenetic marks in germ cells as a mechanism by which parental exposures affect offspring, while discussing both maternal and paternal studies. The citation is attached to that proposed gamete-dependent mechanism; the statement about what blood samples can establish is the citing authors’ uncited qualification. (LLM, conf=0.91)
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“FKBP5 single nucleotide polymorphisms have additionally been shown to interact with early trauma to predict both PTSD and major depression (36,37), possibly through involvement of allelespecific, environmentally dependent changes in methylation of specific cytosine-phosphate-guanine (CpG) sites (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Partly supportedcites [36] Binder, 2008, Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults, JAMA sourceExperimental — accuracy not yet measured
The COMMENT reports that FKBP5 SNPs interacted with child abuse to predict adult PTSD symptoms. The “FKBP5 and Child Abuse Interaction” section reports no significant genotype-by-child-abuse interaction for depression outcome after correction for multiple testing. This source therefore supports the PTSD part, but not the claim about major depression. (LLM, conf=0.90)
- Partly supportedcites [37] Koenen, 2010, FKBP5 polymorphisms modify the effects of childhood trauma, Neuropsychopharmacology sourceExperimental — accuracy not yet measured
The main text reports that FKBP5 SNP rs9470080 interacted with childhood adversity to predict PTSD risk in African-American participants; the interaction was not significant in European Americans. It does not report an FKBP5–early-trauma interaction predicting major depression. The depression study listed in the References concerns CRHR1, not FKBP5. (LLM, conf=0.87)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Partly supported
The cited sources that could be checked couldn’t confirm or dispute this claim.
In the paper
“alterations of which have been associated with both PTSD and intergenerational effects (27,28).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Could not verifycites [27] Lehrner, 2014, Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors, Psychoneuroendocrinology sourceExperimental — accuracy not yet measured
The Results report an association between maternal PTSD and offspring glucocorticoid sensitivity, and the Discussion considers possible intergenerational mechanisms. Neither section identifies FKBP5 or links alterations of it to PTSD or intergenerational effects (searched: FKBP5 and FK506-binding protein 5). (LLM, conf=0.72)
- Not checked — no full text of the sourcecites [28] Daskalakis, 2013, Endocrine aspects of post-traumatic stress disorder and implications for diagnosis and treatment, Endocrinol Metab Clin North Am source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Could not verify
Every source the paper cites for this claim was checked and supports it.
In the paper
“Intron 7 sites are located within, or in proximity to, functional consensus glucocorticoid response elements (GREs) and are demethylated by glucocorticoids, particularly during developmentally sensitive periods (38).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Supportedcites [38] Klengel, 2013, Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions, Nat Neurosci source
The Methods (page not supplied) locate the intron 7 CpG sites within or near consensus GREs. The Results (page not supplied) report dexamethasone-induced demethylation of those sites and a sensitive period during which glucocorticoid exposure produced the effect. (LLM, conf=0.94)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“FKBP5 gene expression has been shown to be altered in PTSD and major depression (32)(33)(34)(35).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Supportedcites [32] Menke, 2013, Genetic variation in FKBP5 associated with the extent of stress hormone dysregulation in major depression, Genes Brain Behav source
The Abstract (page unavailable) reports genotype-specific gene-expression changes in PTSD. The Stimulated FKBP5 mRNA expression section (page unavailable) reports a significant difference in FKBP5 mRNA induction between depressed patients and controls carrying the same risk allele. Together, these passages support the broad claim that FKBP5 expression is altered in both conditions. (LLM, conf=0.88)
- Partly supportedcites [33] Mehta, 2011, Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies, Arch Gen Psychiatry sourceExperimental — accuracy not yet measured
The Results and Comment sections report genotype-dependent changes in FKBP5 expression associated with PTSD symptoms, including a replicated association. The passages do not report altered FKBP5 expression in major depression, so this source supports only the PTSD part of the claim. Page numbers were not provided in our copy. (LLM, conf=0.88)
- Partly supportedcites [34] Sarapas, 2011, Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks, Dis Markers sourceExperimental — accuracy not yet measured
The genetic analysis (§3.3; page unavailable) links lower FKBP5 expression to greater PTSD symptom severity. The Discussion (§4; page unavailable) does not establish altered FKBP5 gene expression in major depression: it reports that a depression-associated genotype was not related to FKBP5 mRNA expression, although it was associated with higher protein levels. (LLM, conf=0.88)
- Supportedcites [35] Yehuda, 2009, Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks, Biol Psychiatry source
The Results report significantly decreased FKBP5 expression in participants with PTSD. The Discussion also reports that FKBP5 expression in recurrent depression was altered in the opposite direction; the paper does not present that depression finding as its own experiment. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Indeed, for the NR3C1 gene, associations of individual sites with exposures to several types of adversity are increasingly recognized (52).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Supportedcites [52] Daskalakis, 2014, Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: Systematic review of contributing factors, Front Neurosci source
The GR-1F promoter site-specific methylation section reviews site-specific NR3C1 methylation findings across 16 studies. It identifies associations with several forms of adversity, including prenatal maternal mood, childhood abuse, parental loss, and other early stressful events. The supplied passages do not provide page numbers. (LLM, conf=0.93)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- 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
“The main finding in this study is that Holocaust survivors and their offspring have methylation changes on the same site in a functional intronic region of the FKBP5 gene, a GR-binding sequence in intron 7, but in the opposite direction.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Neither parental PTSD (β 5 .134,ns) nor the presence of the FKBP5 risk allele (β 5 2.044, ns) contributed to the model.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > FKBP5 Intron 7 Methylation Holocaust Offspring and F1 Comparison Subjects
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“However, like the CTQ total score, emotional abuse was not significantly associated with bin 3/site 6 methylation (β 5 .018,ns) and did not alter the significance of Holocaust exposure at this site (β 5 2.375, p 5 .045).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > FKBP5 Intron 7 Methylation Holocaust Offspring and F1 Comparison Subjects
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“Adding childhood adversity as measured by the CTQ total score did not alter the predictive significance of parental exposure (β 5 2.359, p 5 .049)and was not a predictor of bin 3/site 6 methylation (β 5 2.034, ns).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > FKBP5 Intron 7 Methylation Holocaust Offspring and F1 Comparison Subjects
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“The mechanism of intergenerational transmission of epigenetic effects at bin 3/site 6 is not known but does not appear to be mediated by childhood adversity, as is the case for bin 2.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Biological Psychiatry
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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
“In contrast to the findings at bin 3/site 6, which relate to parental exposure, bin 2/sites 3 to 5 methylation was associated with offspring trauma exposure (childhood physical and sexual abuse), but the direction depended on the presence of the FKBP5 risk allele.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“It should be noted that mean CTQ subscale and total scores for the Holocaust offspring were generally lower than reported in other population samples”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Parental trauma exposure is associated with greater risk for posttraumatic stress disorder (PTSD) and mood and anxiety disorders in offspring (1,2).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Abstract
What the sources say
- Not checked — no full text of the sourcecites [1] Yehuda, 1998, Vulnerability to posttraumatic stress disorder in adult offspring of Holocaust survivors, Am J Psychiatry source
- Not checked — no full text of the sourcecites [2] Weissman, 2005, Families at high and low risk for depression: A 3-generation study, Arch Gen Psychiatry source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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 finding was unchanged without covariation (F 1,29 5 4.91, p 5 .035)and when presence of lifetime PTSD in offspring (p 5 .036)or severity of childhood trauma (p 5 .049)were added, respectively, as additional covariates.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > FKBP5 Intron 7 Methylation Holocaust Offspring and F1 Comparison Subjects
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Bin 3/site 6 methylation was not associated with the FKBP5 risk allele and could not be attributed to the offspring's own trauma exposure, their own psychopathology, or other examined characteristics that might independently affect methylation of this gene.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“in the aforementioned study, the increase in offspring 11β-HSD-2 activity was interpreted as a protective adaptation to mitigate exposure to elevated maternal glucocorticoids associated with reduced maternal 11β-HSD-2 activity (20,50).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Not checked — no full text of the sourcecites [20] Bierer, 2014, Elevation of 11beta-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: Evidence for an intergenerational effect of maternal trauma exposure, Psychoneuroendocrinology source
- Not checked — no full text of the sourcecites [50] Yehuda, 2011, Minireview: Stress-related psychiatric disorders with low cortisol levels: A metabolic hypothesis, Endocrinology source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“The addition of presence/absence of the FKBP5 risk allele as a covariate did not appreciably alter the finding (p 5 .053),suggesting that bin 3/site 6 methylation changes in F0 were driven more by exposure than genetic variation in this single nucleotide polymorphism.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > FKBP5 Intron 7 Methylation in Holocaust Survivors and F0 Comparison Subjects
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“We previously reported a directional difference between parents and offspring in 11β-HSD-2 activity, which was interpreted as an accommodation in the offspring during a sensitive developmental window to the biological consequences of parental trauma exposure (20).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Not checked — no full text of the sourcecites [20] Bierer, 2014, Elevation of 11beta-hydroxysteroid dehydrogenase type 2 activity in Holocaust survivor offspring: Evidence for an intergenerational effect of maternal trauma exposure, Psychoneuroendocrinology source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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
“Like FKBP5, 11β-HSD-2 is a moderator of glucocorticoid action”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“The directional difference in bin 3/site 6 methylation between Holocaust survivors and their offspring was unexpected but may reflect an intergenerational biological accommodation.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
Strength:hedged· not yet calibratedCausal:conditional· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In turn, FKBP5 gene expression is regulated by GR binding, forming an intracellular ultrashort glucocorticoid negative-feedback loop that regulates FKBP5 and GR (26,31).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > SEE COMMENTARY ON PAGE
What the sources say
- Not checked — no full text of the sourcecites [26] Binder, 2009, The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders, Psychoneuroendocrinology source
- Not checked — no full text of the sourcecites [31] Jaaskelainen, 2011, Steroid up-regulation of FKBP51 and its role in hormone signaling, Curr Opin Pharmacol source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“There were no significant differences between the groups in age, gender, years of education, current anxiety or mood disorder diagnoses, or frequency of the FKBP5 risk allele.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Survivor and Comparison Group Demographic Characteristics
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“There were no significant differences between the groups in age, gender, years of education, childhood trauma scores, psychiatric diagnoses, frequency of the FKBP5 risk allele, or cortisol levels.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Offspring and Comparison Group Demographic Characteristics
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“In contrast, the effect was reduced when controlling for parental PTSD (F 1,23 5 2.59, p 5 .121),suggesting an influence of parental PTSD symptoms.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > FKBP5 Intron 7 Methylation Holocaust Offspring and F1 Comparison Subjects
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“Genotypes of rs1360780 were in Hardy-Weinberg equilibrium (p ..05).”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Genotyping.
Strength:plain· not yet calibratedn = 71Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In addition, even within the same cell type, observed global changes reflect diverse changes in single cells, as has been reported in a number of articles using clone-based sequencing for methylation analysis [for example (16,17,54)].”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Holocaust Exposure and Intergenerational FKBP5 Methylation
What the sources say
- Not checked — no full text of the sourcecites [16] Weaver, 2004, Epigenetic programming by maternal behavior, Nat Neurosci source
- Not checked — no full text of the sourcecites [17] Murgatroyd, 2009, Dynamic DNA methylation programs persistent adverse effects of early-life stress, Nat Neurosci source
- Not checked — no full text of the sourcecites [54] Yehuda, 2015, Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder, Biol Psychiatry source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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
“All F1 participants were raised by their biological parents.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > METHODS AND MATERIALS Sample
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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 intra-assay and interassay coefficients of variation were 2.3% and 6.1%, respectively.”
§ Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation > Hormone Measurement.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
A major gap in the clinical literature is that parents and their adult offspring have not been studied in tandem, making it difficult to understand the origin of changes in association with parental exposure.
“A major gap in the clinical literature is that parents and their adult offspring have not been studied in tandem, making it difficult to understand the origin of changes in association with parental exposure.”
The paper relies on this without support.
What can be detected in blood samples is parental and offspring experience-dependent epigenetic modifications.
“What can be detected in blood samples is parental and offspring experience-dependent epigenetic modifications.”
The paper relies on this without support.
The observed associations between parental Holocaust exposure and offspring FKBP5 methylation reflect intergenerational transmission of epigenetic effects rather than preconception or postnatal influences or offspring recalibration of glucocorticoid regulation.
“At present, it is not clear whether glucocorticoid programming in offspring reflects intergenerational consequences of parental exposure or offspring recalibration of glucocorticoid regulation.”
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?
The cited source doesn’t support the claim as written.
In the citing paper
“This finding tends to contradict previous findings where FKBP5 methylation has been associated with PTSD (e.g., Yehuda et al., 2016;Methal et al., 2019).”
From DNA methylation of NR3C1 and FKBP5 is associated with posttraumatic stress disorder, posttraumatic growth, and resilience. (2020) · cites this paper as Yehuda et al., 2016
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Across survivor populations and their descendants, research suggests coordinated involvement of stress-response regulation, neurodevelopmental signaling, and behavioral adaptation (7, 82–100).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [83]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Studies of Holocaust survivors and their offspring demonstrate differential DNA methylation of key HPA-axis genes, including NR3C1 and FKBP5, corresponding with variation in glucocorticoid receptor sensitivity and cortisol feedback regulation (82, 83).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [83]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Variation in FKBP5 methylation across intronic regions has also been reported, with opposite directional patterns observed in survivors and their offspring, corresponding with differences in FKBP5 expression and glucocorticoid receptor sensitivity (83, 84).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [83]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“FKBP5 methylation differences have been reported across multiple trauma contexts in both survivors and offspring, raising the possibility that stress-response regulatory genes may help distinguish individuals more likely to benefit from specific interventions (38, 66, 83, 84, 136).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [83]
Experimental — accuracy not yet measured
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A substantial proportion of studies have focused on a limited number of stress-response genes, most notably FKBP5 and NR3C1 (55, 65, 83, 84, 121, 129).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [83]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“For example, a preliminary study examining FKBP5 intron 7 methylation in Holocaust survivors and their children demonstrated alterations at the same site within intron 7 in both parents and their children, with no specific consideration of parental gender or PTSD 127 .”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [127]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“In 32 Holocaust survivors and their 22 adult offspring compared to eight non-exposed control parents and their nine children, parental Holocaust exposure was found to predict FKBP5 intron 7 methylation in offspring.”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Yehuda et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“Methylation of the third GRE in intron 7 was further positively correlated with methylation at the same site in their offspring and overall average methylation of intron 7 was negatively correlated with wake-up cortisol”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Yehuda et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“Furthermore, offspring carrying the FKBP5 rs1360780 A risk allele showed a significant negative correlation between the degree of physical and sexual childhood abuse and CpG methylation across the first GRE in intron 7, while G/G genotype carriers displayed a positive correlation”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Yehuda et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“Of note, increased whole blood CpG methylation was observed in the third (of a total of three) GRE of FKBP5 intron 7 in Holocaust survivors compared to contemporary Jewish controls, while children of Holocaust survivors were characterized by decreased methylation compared to control children”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Yehuda et al., 2016
The cited source says what the claim attributes to it.
In the citing paper
“Potential epigenetic effects in maternal or paternal gametes could not, however, be investigated.”
The cited source says what the claim attributes to it.
In the citing paper
“Exposed parents had an average of 10% higher methylation compared to unexposed, while exposed offspring had 7.7% lower methylation.”
The cited source says what the claim attributes to it.
In the citing paper
“In their analysis, Yehuda and colleagues also controlled for current PTSD (51.6% of the Holocaust-exposed parents), childhood trauma in the offspring, or genetic variation in the gene.”
The cited source says what the claim attributes to it.
In the citing paper
“Holocaust exposure was associated with blood DNA methylation of the FKBP5 gene at the same transcriptionally active site in both generations, although interestingly in opposing directions.”
The cited source says what the claim attributes to it.
In the citing paper
“The majority of the studies looked at only maternal transmission, but four considered both maternal and paternal [83,94,95,102], and two focused only on fathers [97,104].”
The cited source says what the claim attributes to it.
In the citing paper
“Of the five studies that measured FKBP5 DNA methylation, three found lower methylation in the offspring of exposed parents [83,94,99], one found an opposite association with higher methylation [103], and another reported no association [88].”
The cited source says what the claim attributes to it.
In the citing paper
“There were six studies of trauma or PTSD following war, including two studies of Holocaust survivors [83,94,95], two studies on the Rwandan genocide [90,91], and one each from the Kosovo War [96] and Vietnam veterans [97].”
The cited source says what the claim attributes to it.
In the citing paper
“However, interestingly, they were directionally distinct (when compared to their respective control groups), with Holocaust offspring showing lower methylation at this site compared to demographically-matched controls, and Holocaust survivors demonstrating higher methylation compared to respective controls.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [127]
The cited source says what the claim attributes to it.
In the citing paper
“FKBP5 methylation in parents and their children were positively correlated.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [127]
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“While hypothesis-driven candidate gene studies can provide mechanistic insight, narrow locus selection risks overemphasizing the importance of specific genes while overlooking broader regulatory networks (83, 84, 121, 129).”
From Epigenetic changes associated with multi-generational trauma: characterization, mechanisms, and therapeutics (2026) · cites this paper as [83]
Experimental — accuracy not yet measuredIn the citing paper
“Multiple human studies have indicated that traumas such as combat exposure, forced displacement, genocide exposure, and low maternal bonding may be passed on inter-generationally, and have been associated with both psychopathology in children and DNA methylation in the FKBP5 gene.45,46”
From The role of epigenetics in psychological resilience (2021) · cites this paper as [46]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Control offspring trauma total does not match its subscales
MinorThe five listed mean trauma subscale scores for comparison offspring sum to 35.6, not the reported total mean of 30.2. The gap exceeds what rounding the subscale means could explain.
Reported 30.2 · recomputed 35.6
“| Total score | 36.7 6 11.5 | 30.2 6 6.9 | F 1,30 5 2.46, ns |”
Emotional-abuse direction conflicts with the table
MinorThe discussion of this sample implies greater emotional abuse among Holocaust offspring, whereas Table 2 lists a lower mean for them than for comparison offspring.
“Since emotional abuse is reported substantially more often by Holocaust survivor offspring (25) and was reported in this sample at a trend level of significance (t 5 21.98, df 5 24.89, p 5 .059),we tested emotional abuse in the regression model.”
“| Emotional abuse | 9.0 6 5.4 | 12.0 6 3.3 | F 1,30 5 2.57, ns |”
A predictor is called significant at p = .054
MinorThe paper sets significance at p < .05 but describes parental exposure as remaining significant in a model where its reported p-value is .054.
“In each of these, however, parental exposure remained a significant predictor (respectively, β 5 2.461, p 5 .054;β 5 2.362, p 5 .043).”
“Finally, statistical significance for all analyses was set at two-tailed, p , .05.”
Offspring anxiety diagnosis differs significantly in the table
MinorThe text says psychiatric diagnoses did not differ between offspring groups, but Table 2 reports a significant difference for current anxiety disorder.
“There were no significant differences between the groups in age, gender, years of education, childhood trauma scores, psychiatric diagnoses, frequency of the FKBP5 risk allele, or cortisol levels.”
“| Current Anxiety Disorder (except PTSD) d | 8 (36.4%) | 0 (0%) | χ 2 1 5 6.56, p 5 .041 |”
Citations
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BackgroundYu, S., Yu, M., Bu, Z., He, P., & Feng, J. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00193 · Cited by 51
Childhood trauma, the stress response and metabolic syndrome: A focus on DNA methylation
Womersley, J. S., Nöthling, J., Toikumo, S., Malan‐Müller, S., van den Heuvel, L. L., McGregor, N. W., Seedat, S., & Hemmings, S. M. J. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.15370 · Cited by 52
Transgenerational epigenetic inheritance of traumatic experience in mammals
Švorcová, J. (2023) · Genes · doi:10.3390/genes14010120 · Cited by 47
Santavirta, T., Santavirta, N., & Gilman, S. E. (2018) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2017.3511 · Cited by 48
Daskalakis, N. P., Xu, C., Bader, H. N., Chatzinakos, C., Weber, P. C., Makotkine, I., Lehrner, A. L., Bierer, L. M., Binder, E. B., & Yehuda, R. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-00900-8 · Cited by 48
Self-citationJowf, G. I. A., Snijders, C., Rutten, B. P. F., de Nijs, L., & Eijssen, L. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910743 · Cited by 52
The public reception of putative epigenetic mechanisms in the transgenerational effects of trauma
Yehuda, R., Lehrner, A. L., & Bierer, L. M. (2018) · Current Zoology · doi:10.1093/eep/dvy018 · Cited by 51
Self-citationCarter, S. E., Gibbons, F. X., & Beach, S. R. H. (2021) · Development and Psychopathology · doi:10.1017/s0954579421001073 · Cited by 47
Frasch, M. G., Lobmaier, S. M., Stampalija, T., Desplats, P., Pallarés, M. E., Pastor, V. E., Brocco, M. A., Wu, H., Schulkin, J. A., Herry, C. L., et al. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.05.026 · Cited by 47
Saldaña‐Tejeda, A. (2017) · BioSocieties · doi:10.1057/s41292-017-0078-8 · Cited by 45
Ullmann, E., Barthel, A., Petrowski, K., Tobias Stalder, A., Kirschbaum, C., & Bornstein, S. R. (2016) · Scientific Reports · doi:10.1038/srep25842 · Cited by 44
Kazlauskas, E., Gailienė, D., Vaskelienė, I., & Skerytė-Kazlauskienė, M. (2017) · Frontiers in Psychology · doi:10.3389/fpsyg.2017.01677 · Cited by 44
“Trauma-related parental stress can produce neuroendocrine, epigenetic, and neuroanatomical changes in offspring as evidenced by genetic and neuroscience research (Bowers and Yehuda, 2016; Yehuda et al., 2016).”
BackgroundMoody, D. L. B., Taylor, A. D., Leibel, D. K., Al-Najjar, E., Katzel, L. I., Davatzikos, C. A., Gullapalli, R. P., Seliger, S. L., Kouo, T., Erus, G., et al. (2018) · Health Psychology · doi:10.1037/hea0000638 · Cited by 45
“Such work has mainly been conducted in Holocaust survivors and their offspring (e.g., Yehuda et al., 2016).”
Getting to Why: Adverse Childhood Experiences' Impact on Adult Health
Bryan, R. H. (2018) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2018.09.012 · Cited by 44
“Epigenetic changes to DNA due to stress persist, and research has demonstrated intergenerational transmission.(25) Exposure to ACEs is also associated with premature shortening of telomeres, the protective end sequences of DNA.”
BackgroundSnoek, A., Beekman, A. T. F., Dekker, J., Aarts, I., van Grootheest, G., Blankers, M., Vriend, C., van den Heuvel, O., & Thomaes, K. (2020) · BMC Psychiatry · doi:10.1186/s12888-020-02713-x · Cited by 44
Palma‐Gudiel, H., Prather, A. A., Lin, J., Oxendine, J. D., Guintivano, J., Xia, K., Rubinow, D. R., Wolkowitz, O. M., Epel, E. S., & Zannas, A. S. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.11.027 · Cited by 47
Intergenerational Transmission of Child Abuse and Neglect: A Transdisciplinary Analysis
Wert, M. V., Anreiter, I., Fallon, B., & Sokolowski, M. B. (2019) · Gender and the Genome · doi:10.1177/2470289719826101 · Cited by 54
HAM-TBS: high-accuracy methylation measurements via targeted bisulfite sequencing
Roeh, S., Wiechmann, T., Sauer, S., Ködel, M., Binder, E. B., & Provençal, N. (2018) · Epigenetics & Chromatin · doi:10.1186/s13072-018-0209-x · Cited by 42
Self-citationRacial disparities in pregnancy outcomes: genetics, epigenetics, and allostatic load
Leimert, K. B., & Olson, D. M. (2019) · Current Opinion in Physiology · doi:10.1016/j.cophys.2019.12.003 · Cited by 41
Systemic racism can get under our skin and into our genes
Mulligan, C. J. (2021) · American Journal of Physical Anthropology · doi:10.1002/ajpa.24290 · Cited by 47
Kim, A. W., Mohamed, R. S., Norris, S. A., Richter, L., & Kuzawa, C. W. (2022) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.13672 · Cited by 48
Sijbrandij, M. (2017) · Epidemiology and Psychiatric Sciences · doi:10.1017/s2045796017000713 · Cited by 39
“Further, an exciting line of research is focused on epigenetic mechanisms in the intergenerational transmission of traumatic stress effects in refugees, and possibilities to interfere with such effects deserve further study (see Yehuda et al. (2016)).”
BackgroundKira, I. A., Shuwiekh, H. A. M., Kucharska, J., Fawzi, M. H., Ashby, J. S., Omidy, A. Z., Abou-Mediene, S., & Lewandowski, L. (2018) · American Journal of Orthopsychiatry · doi:10.1037/ort0000304 · Cited by 43
Aydın, N., & Yıldız, H. (2018) · Journal of Human Sciences · doi:10.14687/jhs.v15i1.5175 · Cited by 40
Bhattacharya, S., Fontaine, A., MacCallum, P. E., Drover, J., & Blundell, J. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00113 · Cited by 40
“…region for FK506 binding protein 5 (FKBP5), a protein that lowers the affinity of cortisol when it is bound to GR; thereby potentially hindering the negative HPA axis feedback loop (Binder, 2009), while methylation at this site was lower in Holocaust survivor offspring (Yehuda et al., 2016).”
BackgroundResultInfluentialCasier, K., Boivin, A., Carré, C., & Teysset, L. (2019) · Cells · doi:10.3390/cells8091108 · Cited by 37
“A restricted number of studies identified epigenetic modifications associated with parental stress [6].”
BackgroundA Review on Epigenetic Inheritance of Experiences in Humans
Ghai, M., & Kader, F. (2021) · Biochemical Genetics · doi:10.1007/s10528-021-10155-7 · Cited by 40
DNA methylation from germline cells in veterans with PTSD
Mehta, D., Pelzer, E. S., Bruenig, D., Lawford, B., McLeay, S., Morris, C. P., Gibson, J. N., Young, R. M., Voisey, J., McLeay, S., et al. (2019) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2019.06.001 · Cited by 37
Mbiydzenyuy, N. E., Hemmings, S. M. J., & Qulu, L. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.977416 · Cited by 44
“One is the transfer of genes that are vulnerable to stress from mother to offspring (Bowers and Yehuda, 2016) and the other is the direct impact of the traumatic stress on the mother affecting her ability to parent her child and the altered childhood environment (Yehuda et al., 2001).”
BackgroundDave, L. A., Hodgkinson, S. M., Roy, N. C., Smith, N. W., & McNabb, W. C. (2021) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2021.2012753 · Cited by 47
Cohn, I. G., & Morrison, N. M. V. (2017) · Australian Journal of Psychology · doi:10.1111/ajpy.12194 · Cited by 40
Refugee and Asylum-Seeking Children: Interrupted Child Development and Unfulfilled Child Rights
Vaghri, Z., Tessier, Z., & Whalen, C. (2019) · Children · doi:10.3390/children6110120 · Cited by 38
Harnett, N. G. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0681-4 · Cited by 41
Opportunities and challenges of big data for the social sciences: The case of genomic data
Liu, H., & Guo, G. (2016) · Social Science Research · doi:10.1016/j.ssresearch.2016.04.016 · Cited by 39
“In another study, Yehuda et al. (2015) showed that holocaust exposure affected FK506 binding protein 5 (FKBP5) methylation that was observed in exposed parents as well in their offspring.”
BackgroundCulture as an ingredient of personalized medicine
Matheson, K., Bombay, A., & Anisman, H. (2017) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.170234 · Cited by 38
Neuroepigenetics of Post-Traumatic Stress Disorder
Kim, G. S., Smith, A. K., Nievergelt, C. M., & Uddin, M. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.04.001 · Cited by 37
The Pathways between Cortisol-Related Regulation Genes and PTSD Psychotherapy
Castro-Vale, I., & Carvalho, D. M. (2020) · Healthcare · doi:10.3390/healthcare8040376 · Cited by 39
The Epigenetics of Early Life Adversity: Current Limitations and Possible Solutions
Barnett-Burns, S., Almeida, D. M., & Turecki, G. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.01.008 · Cited by 35
Reversing Behavioral, Neuroanatomical, and Germline Influences of Intergenerational Stress
Aoued, H. S., Sannigrahi, S., Doshi, N. K., Morrison, F. G., Linsenbaum, H., Hunter, S. C., Walum, H., Baman, J., Yao, B., Jin, P., et al. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.07.028 · Cited by 38
“Trauma like the Holocaust and domestic abuse in humans (31,32), and stress protocols in rodents (3,6,33), are broad in their intergenerational effects.”
BackgroundAfrican American Health and Posttraumatic Slave Syndrome: A Terror Management Theory Account
Halloran, M. J. (2018) · Journal of Black Studies · doi:10.1177/0021934718803737 · Cited by 54
Rieder, A. D., Roth, S. L., Musyimi, C. W., Ndetei, D. M., Sassi, R. B., Mutiso, V., Hall, G. B., & González, A. (2019) · Developmental Science · doi:10.1111/desc.12833 · Cited by 38
Dynamic Changes in DNA Methylation Occur during the First Year of Life in Preterm Infants
Piyasena, C., Cartier, J., Provençal, N., Wiechmann, T., Khulan, B., Sunderesan, R., Menon, G. N., Seckl, J. R., Reynolds, R. M., Binder, E. B., et al. (2016) · Frontiers in Endocrinology · doi:10.3389/fendo.2016.00158 · Cited by 36
“” In vivo and in vitro studies have shown that glucocorticoid exposure leads to stable DNA demethylation at these specific sites within the FKBP5 locus (20, 39), and several studies have now shown that exposure to trauma during childhood associates with allele-specific demethylation at FKBP5 in adulthood (20, 40).”
BackgroundSelf-citationHousen, T., Lenglet, A., Shah, S., Sha, H., Ara, S., Pintaldi, G., & Richardson, A. (2019) · Conflict and Health · doi:10.1186/s13031-019-0245-6 · Cited by 38
The potential of epigenetics in stress-enhanced fear learning models of PTSDPreprint
Blouin, A. M., Sillivan, S. E., Joseph, N. F., & Miller, C. A. (2016) · Learning & Memory · doi:10.1101/lm.040485.115 · Cited by 37
“A reduction in FKBP5 levels have been reported in PTSD patients (Yehuda et al. 2009), and changes in methylation of the FKBP5 gene have been found in holocaust survivors and their offspring (Yehuda et al. 2015a).”
BackgroundInfluentialMulligan, C. J., Quinn, E. B., Hamadmad, D., Dutton, C. L., Nevell, L., Binder, A. M., Panter-Brick, C., & Dajani, R. (2025) · Scientific Reports · doi:10.1038/s41598-025-89818-z · Cited by 36
“Specifically, maternal stress and trauma have been associated with changes in newborn DNAm and epigenetic age acceleration as well as indicators of worsened health outcomes such as diabetes 18–22 .”
How to Make DNA Methylome Wide Association Studies More Powerful
Lin, X., Barton, S. J., & Holbrook, J. D. (2016) · Epigenomics · doi:10.2217/epi-2016-0017 · Cited by 33
Epigenetic Programming Effects of Early Life Stress: A Dual-Activation Hypothesis
Lux, V. (2018) · Current Genomics · doi:10.2174/1389202919666180307151358 · Cited by 40
“even reported tentative evidence of transgenerational effects of differential DNA methylation at the Fkbp5 intron 7 in blood cells of Holocaust survivors and their offspring compared to controls, possibly indicating a long-term programming effect across generations [73].”
BackgroundConstitutional Mosaic Epimutations – a hidden cause of cancer?
Lønning, P. E., Eikesdal, H. P., Løes, I. M., & Knappskog, S. (2019) · Cell Stress · doi:10.15698/cst2019.04.183 · Cited by 33
“Merging evidence indicates trans-generational responses also in humans [189, 190].”
BackgroundFourie, M. M., Stein, D. J., Solms, M., Gobodo‐Madikizela, P., & Decety, J. (2019) · Scientific Reports · doi:10.1038/s41598-019-49298-4 · Cited by 39
Li, S., Hu, W., Deng, F., Chen, S., Zhu, P., Wang, M., Chen, X., Wang, Y., Hu, X., Zhao, B., et al. (2021) · DNA and Cell Biology · doi:10.1089/dna.2020.5662 · Cited by 35
“In addition, FKBP5 may interact with in-flammatory factors, and the upregulation of FKBP5 may promote the regulation of nuclear factor-kappa B to kinases and inflammation in cardiovascular diseases (Vac-carino et al. , 2013, Yehuda et al. , 2016).”
Focusing on Racial, Historical and Intergenerational Trauma, and Resilience
Fortuna, L. R., Tobón, A. L., Anglero, Y. L., Postlethwaite, A., Porche, M. V. M., & Rothe, E. M. (2022) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2021.11.004 · Cited by 38
Musanabaganwa, C., Wani, A. H., Donglasan, J., Fatumo, S., Jansen, S., Mutabaruka, J., Rutembesa, E., Uwineza, A., Hermans, E. J., Roozendaal, B., et al. (2022) · Epigenomics · doi:10.2217/epi-2021-0310 · Cited by 35
A Review of the Impact of Maternal Prenatal Stress on Offspring Microbiota and Metabolites
Yeramilli, V. A., Cheddadi, R., Shah, J., Brawner, K. M., & Martin, C. A. (2023) · Metabolites · doi:10.3390/metabo13040535 · Cited by 38
Mental health dished up—the use of iPSC models in neuropsychiatric research
McNeill, R. V., Ziegler, G. C., Radtke, F., Nieberler, M., Lesch, K., & Kittel‐Schneider, S. (2020) · Journal of Neural Transmission · doi:10.1007/s00702-020-02197-9 · Cited by 32
“These genes are additionally involved in neurodevelopmental processes, further supporting a possible role in ADHD etiology (Hu et al. 2011) (Breiderhoff et al. 2013) (Yoo et al. 2015) (Chen et al. 2016).”
BackgroundHaq, S. U., Bhat, U. A., & Kumar, A. (2021) · Journal of Biosciences · doi:10.1007/s12038-021-00153-7 · Cited by 37
Ellis, A. S., Toussaint, A. B., Knouse, M. C., Thomas, A. S., Bongiovanni, A. R., Mayberry, H. L., Bhakta, S., Peer, K., Bangasser, D. A., & Wimmer, M. E. (2020) · Psychopharmacology · doi:10.1007/s00213-019-05450-6 · Cited by 33
“Multigenerational and transgenerational effects of paternal insults such as stress and diet have been reported in humans (Kaati et al. 2002; Pembrey et al. 2006; Radley et al. 2011; Yehuda et al. 2016; Yehuda and Lehrner 2018) but are intrinsically difficult to study and remain highly debated.”
Morgan, C. P., Shetty, A. C., Chan, J. C., Berger, D. S., Ament, S. A., Epperson, C. N., & Bale, T. L. (2020) · Scientific Reports · doi:10.1038/s41598-020-73867-7 · Cited by 33
Provenzi, L., Grumi, S., Giorda, R., Biasucci, G., Bonini, R., Cavallini, A. R., Decembrino, L., Drera, B. A., Falcone, R., Fazzi, E. M., et al. (2020) · BMJ Open · doi:10.1136/bmjopen-2020-044585 · Cited by 32
Lebow, M., Schroeder, M., Tsoory, M., Holzman-Karniel, D., Mehta, D., Ben‐Dor, S., Gil, S., Bradley, B., Smith, A. K., Jovanović, T., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0509-3 · Cited by 37
Self-citationKahn, S., & Denov, M. S. (2022) · Transcultural Psychiatry · doi:10.1177/13634615221080231 · Cited by 36
“Extreme stress during pregnancy has been shown to be a factor in the epigenetic transmission of trauma (Perroud et al., 2014; Yehuda, & Lehrner, 2018; Yehuda et al., 2016).”
BackgroundSante, J. D., Ismaylova, E., Nemoda, Z., Gouin, J., Yu, W.-J., Caldwell, W., Vitaro, F., Szyf, M., Tremblay, R. E., & Booij, L. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.07.019 · Cited by 33
On the role of epigenetic modifications of HPA axis in posttraumatic stress disorder and resilience
Khan, Z., Messiri, N. E., Iqbal, E., Hassan, H., Tanweer, M. S., Sadia, S. R., Taj, M., Zaidi, U., Yusuf, K., Syed, N. I., et al. (2025) · Journal of Neurophysiology · doi:10.1152/jn.00345.2024 · Cited by 32
Rodríguez, N., Buxó, C. J., Morou-Bermúdez, E., Pérez‐Edgar, K. E., Ocasio‐Quiñones, I. T., Surillo‐González, M. B., & Martínez, K. (2021) · Developmental Psychobiology · doi:10.1002/dev.22195 · Cited by 30
Lewis, C. R., Tafur, J., Spencer, S., Green, J. M., Harrison, C., Kelmendi, B., Rabin, D. M., Yehuda, R., Yazar‐Klosinski, B., & Cahn, B. R. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.959590 · Cited by 32
“For example, previous studies have focused on the promoter region in intron seven of the FKBP5 gene, demonstrating epigenetic changes correlating with trauma exposure and PTSD symptomatology (14, 15, 54).”
BackgroundSelf-citationRizavi, H. S., Khan, O. S., Zhang, H., Bhaumik, R., Grayson, D. R., & Pandey, G. N. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02345-1 · Cited by 31
360-Degree Perspectives on Obesity
Cuciureanu, M. D., Caratașu, C.-C., Gabrielian, L., Frăsinariu, O. E., Checheriță, L. E., Trandafir, L. M., Stanciu, G. D., Szilagyi, A., Pogonea, I., Bordeianu, G., et al. (2023) · Medicina · doi:10.3390/medicina59061119 · Cited by 33
Intergenerational Transmission of Trauma: Maternal Trauma–Related Cognitions and Toddler Symptoms
Fenerci, R. L. B., & DePrince, A. P. (2017) · Child Maltreatment · doi:10.1177/1077559517737376 · Cited by 31
“Future studies should explore whether mothers’ trauma–related cognitions could interact with established genetic/epigenetic mechanisms (e.g., Yehuda et al., 2016) in explaining the intergenerational transmission of trauma.”
BackgroundBinder, E. B. (2017) · European Journal of Psychotraumatology · doi:10.1080/20008198.2017.1412745 · Cited by 29
Self-citationGenetics of stress-related disorders
Gottschalk, M. G., & Domschke, K. (2020) · doi:10.1093/med/9780198713005.003.0080 · Cited by 29
Plasticity of Sensorimotor Networks
Buch, E. R., Liew, S., & Cohen, L. G. (2016) · The Neuroscientist · doi:10.1177/1073858416638641 · Cited by 30
Razoux, F., Russig, H. D., Mueggler, T., Baltes, C., Dikaiou, K., Rudin, M., & Mansuy, I. M. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.146 · Cited by 29
“These Things Continue”: Violence as Contamination in Everyday Life After War in Northern Uganda
Meinert, L., & Whyte, S. R. (2017) · Ethos · doi:10.1111/etho.12161 · Cited by 33
MicroRNAs in Post-traumatic Stress Disorder
Snijders, C., de Nijs, L., Baker, D. G., Hauger, R. L., van den Hove, D., Kenis, G., Nievergelt, C. M., Boks, M. P., Vermetten, E. H. G. J. M., Gage, F. H., et al. (2017) · Current topics in behavioral neurosciences · doi:10.1007/7854_2017_32 · Cited by 31
Cordero, M. I., Stenz, L., Moser, D. A., Rusconi Serpa, S., Paoloni-Giacobino, A., & Schechter, D. S. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.919820 · Cited by 27
“(9) reported a significant positive correlation of methylation in another gene that also regulates glucocorticoid receptor activity (FK506 binding protein 5, FKBP5) between parents and their offspring, in a sample including Holocaust survivors (n = 32) and match controls (n = 8) and their adult offspring (Holocaust of…”
BackgroundPerinatal stress and epigenetics.
(2021) · Handbook of Clinical Neurology · doi:10.1016/b978-0-12-820107-7.00008-2 · Cited by 28
Reviewing the epigenetics of schizophrenia
Cromby, J., Chung, E. M. L., Papadopoulos, D., & Talbot, C. J. (2016) · Journal of Mental Health · doi:10.1080/09638237.2016.1207229 · Cited by 29
“For example, Yehuda et al. (2015) claim to have found evidence for increased methylation, amongst both Holocaust survivors and their children, at gene sites associated with stress reactivity.”
BackgroundVerstraeten, B. S. E., McCreary, J. K., Weyers, S., Metz, G. A. S., & Olson, D. M. (2019) · Biology of Reproduction · doi:10.1093/biolre/ioy166 · Cited by 28
Flasbeck, V., & Brüne, M. (2021) · PLoS ONE · doi:10.1371/journal.pone.0248514 · Cited by 29
Neonatal NR3C1 Methylation and Social-Emotional Development at 6 and 18 Months of Age
Folger, A. T., Ding, L., Ji, H., Yolton, K. A., Ammerman, R. T., Ginkel, J. B. V., & Bowers, K. A. (2019) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2019.00014 · Cited by 30
“However, this study was exploratory, and studies of similar size and focus have contributed to the emerging field (Stroud et al., 2016; Yehuda et al., 2016).”
ResultEpigenetic Mechanisms Activated by Childhood Adversity
Krause, B. J., Artigas, R., Sciolla, A., & Hamilton, J. (2020) · Epigenomics · doi:10.2217/epi-2020-0042 · Cited by 29
Update on the neurodevelopmental theory of depression: is there any 'unconscious code'?
Gałecka, M., Bliźniewska-Kowalska, K., Maes, M., Su, K.-P., & Gałecki, P. (2021) · Pharmacological Reports · doi:10.1007/s43440-020-00202-2 · Cited by 27
Metabolic Enhancement of the Soldier Brain
Friedl, K. E., & Grate, S. J. (2019) · Oxford University Press eBooks · doi:10.1093/oso/9780190455132.003.0002 · Cited by 29
Climate Changes Affect Human Capital
Caruso, G. D., de Marcos, I., & Noy, I. (2024) · Economics of Disasters and Climate Change · doi:10.1007/s41885-023-00140-2 · Cited by 34
“Another study found that the children of the survivors of the Holocaust had epigenetic changes to a gene linked to their cortisol levels, a hormone involved in stress responses (Yehuda et al. 2016).”
Transgenerational epigenetic inheritance: a critical perspective
Bird, A. P. (2024) · Frontiers in Epigenetics and Epigenomics · doi:10.3389/freae.2024.1434253 · Cited by 32
“…this, a report that exposure to the horrors of the Holocaust during the second world war had adverse consequences for the children of survivors (Yehuda et al., 2016) made headline news, despite numerous technical weakness (e.g., a sample of only 32 people, limited controls and unclear…”
Shields, A. E. (2017) · Epigenomics · doi:10.2217/epi-2017-0013 · Cited by 27
Gendered imaginaries: situating knowledge of epigenetic programming of health
Chiapperino, L., & Panese, F. (2018) · Sociology of Health & Illness · doi:10.1111/1467-9566.12779 · Cited by 27
Exposure to drugs of abuse induce effects that persist across generations
Baratta, A. M., Rathod, R. S., Plasil, S. L., Seth, A., & Homanics, G. E. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.08.003 · Cited by 29
Half a Century of Research on Posttraumatic Stress Disorder: A Scientometric Analysis
Sabé, M., Chen, C., El‐Hage, W., Leroy, A., Vaïva, G., Monari, S., Prémand, N., Bartolomei, J., Caiolo, S., Maercker, A. R. A., et al. (2023) · Current Neuropharmacology · doi:10.2174/1570159x22666230927143106 · Cited by 31
“Importantly, mutation of the FKBP5 gene [71], which is a major regulator of glucocorticoid receptor (GR) sensitivity, has been linked to a higher risk of developing PTSD, especially in individuals who experience childhood abuse (Binder et al. JAMA 2008) or war scenarios [72].”
BackgroundUpdates in PTSD Animal Models Characterization
Zhang, L., Hu, X., Li, H., Li, X., Yu, T., Dohl, J., & Ursano, R. J. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9554-7_19 · Cited by 30
Doherty, T. S., & Roth, T. L. (2016) · Development and Psychopathology · doi:10.1017/s095457941600081x · Cited by 27
“It is interesting that epigenetic effects have been seen in this gene in the offspring of Holocaust survivors, with survivors exhibiting higher FKBP5 methylation and their adult offspring exhibiting lower levels (Yehuda et al., 2015).”
BackgroundInsights from epigenetic studies on human health and evolution
Mulligan, C. J. (2018) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2018.06.008 · Cited by 25
Cissé, Y. M., Chan, J. C., Nugent, B. M., Banducci, C., & Bale, T. L. (2020) · Placenta · doi:10.1016/j.placenta.2020.06.019 · Cited by 28
Emerging trends in epigenetic and childhood trauma: Bibliometrics and visual analysis
Nie, Y., Wen, L., Song, J., Wang, N., Huang, L., Gao, L., & Qu, M. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.925273 · Cited by 28
“Furthermore, trauma experience can also have intergenerational effect on FKBP5 methylation (34).”
BackgroundNeighborhood Deprivation and DNA Methylation and Expression of Cancer Genes in Breast Tumors
Jenkins, B. D., Rossi, E. L., Pichardo, C. M., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2023.41651 · Cited by 25
Metadata
- Authors
- Yehuda, R., Daskalakis, N. P., Bierer, L. M., Bader, H. N., Klengel, T., Holsboer, F., & Binder, E. B.
- Affiliations
- James J. Peters VA Medical Center (US)
- Mount Sinai Hospital (US)
- Emory University (US)
- HolsboerMaschmeyer NeuroChemie (Germany) (DE)
- Corresponding author
- Yehuda, Rachel
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 80
- Issue
- 5
- Pages
- 372-380
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W1203252705
- Cited by
- 782
- References
- 60
- Citations by year
- 2026: 58 · 2025: 90 · 2024: 68 · 2023: 55 · 2022: 65 · 2021: 66 · 2020: 99 · 2019: 75 · 2018: 75 · 2017: 74 · 2016: 47
- FWCI
- 29.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- NIMH (R01 MH 64675-01)
- Biology of Risk and PTSD in Holocaust Survivor Offspring (1RC1MH088101-01)
- Mount Sinai General Clinical Research Center from the National Institute of Health (5 M01 RR00071)
- European Research Council starting (281338)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- Holocaust survivors, intergenerational trauma, FKBP5, DNA methylation, epigenetics, glucocorticoid response element, childhood abuse, cortisol, parental trauma, site-specific methylation
- MeSH terms
- Tacrolimus Binding Protein 5, Cytosine, Female, Humans, Male, Parents, Psychiatric Status Rating Scales, Surveys and Questionnaires, Stress Disorders, Post-Traumatic, Cohort Studies, Child of Impaired Parents, Survivors, Holocaust, DNA Methylation, Tacrolimus Binding Proteins, Adult Children
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.
A language model drew the claims from the paper on 2026-10-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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