The DOI matches its Crossref record; 214 of the 214 references it cites were found in a registry or an index; 87 of the 154 sources its claims cite were checked for support.
Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms
Open accessAbstract
This paper reviews the research evidence concerning the intergenerational transmission of trauma effects and the possible role of epigenetic mechanisms in this transmission. Two broad categories of epigenetically mediated effects are highlighted. The first involves developmentally programmed effects. These can result from the influence of the offspring's early environmental exposures, including postnatal maternal care as well as in utero exposure reflecting maternal stress during pregnancy. The second includes epigenetic changes associated with a preconception trauma in parents that may affect the germline, and impact fetoplacental interactions. Several factors, such as sex‐specific epigenetic effects following trauma exposure and parental developmental stage at the time of exposure, explain different effects of maternal and paternal trauma. The most compelling work to date has been done in animal models, where the opportunity for controlled designs enables clear interpretations of transmissible effects. Given the paucity of human studies and the methodological challenges in conducting such studies, it is not possible to attribute intergenerational effects in humans to a single set of biological or other determinants at this time. Elucidating the role of epigenetic mechanisms in intergenerational effects through prospective, multi‐generational studies may ultimately yield a cogent understanding of how individual, cultural and societal experiences permeate our biology.
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46 Own interpretation · 33 Partly supported · 32 No full text of the sources · 29 Supported · 8 No basis given · 7 Sources not found · 6 Supported so far · 5 Own method · 2 Not checked yet · 1 Not supported · 1 Couldn’t confirm · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Lower cortisol and blunted cortisol reactivity were present in preadolescent boys and girls with maternal PTSD, even after controlling for youth traumatic event history and mental health symptoms 73 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Partly supportedcites [73] 73. Danielson CK, Hankin BL, Badanes LS. Youth offspring of mothers with posttraumatic stress disorder have altered stress reactivity in response to a laboratory stressor. Psychoneuroendocrinology 2015;53:170-8. sourceExperimental — accuracy not yet measured
The Results (§3.3) report a flat, blunted cortisol response in offspring of mothers with PTSD, with group differences maintained after controlling for youth traumatic event history, depressive symptoms, and physical anxiety symptoms. The Discussion (§4) describes low stress-provoked cortisol levels. However, the Methods (§2.1) give an age range of 9–15 years, so describing the entire sample as preadolescent is too narrow. (LLM, conf=0.86)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“An interaction of maternal and paternal PTSD on urinary cortisol and the DST demonstrated a decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Supportedcites [63] 63. Lehrner A, Bierer LM, Passarelli V et al. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors. Psy- choneuroendocrinology 2014;40:213-20. source
The Abstract states that the interaction of maternal and paternal PTSD on the DST and 24-hour urinary cortisol showed decreased glucocorticoid sensitivity in offspring with paternal, but not maternal, PTSD. The Discussion clarifies that this pattern occurred with paternal PTSD only; when maternal PTSD was also present, offspring showed increased sensitivity. (LLM, conf=0.94)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Epigenetic modifications impact gene function by altering gene regulatory elements that affect the action of gene transcription factors 91 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > RELEVANCE OF EPIGENETIC MECHANISMS TO INTERGENERATIONAL EFFECTS
What the sources say
- Supportedcites [91] 91. Meaney MJ, Szyf M. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environ- ment and a fixed genome. Dialogues Clin Neurosci 2005;7:103-23. source
In “The chemistry of DNA methylation” (page not provided), the paper explains that methylation within a transcription-factor response element reduces the factor’s binding affinity. The section on site-specific methylation of the NGFIA response element likewise reports that methylation interferes with NGFIA binding, supporting the claimed effect on gene regulation. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“For example, lower cortisol levels were observed in the adult offspring of combat veterans with PTSD compared to offspring of combat veterans without PTSD 65 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Partly supportedcites [65] 65. Yahyavi ST, Zarghami M, Naghshvar F et al. Relationship of cortisol, nor- epinephrine, and epinephrine levels with war-induced posttraumatic stress disorder in fathers and their offspring. Rev Bras Psiquiatr 2015;37:93-8. sourceExperimental — accuracy not yet measured
The Discussion’s Table 5 reports lower afternoon cortisol in offspring of veterans with a PTSD history than in offspring of veterans without one, following a post-hoc regrouping. But the Discussion says the offspring groups were, on average, adolescents, so the claim’s description of them as adult offspring is not supported. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
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In the paper
“A blunted cortisol reactivity to stress was observed in even younger offspring, toddlers aged 12-48 months, in association with maternal PTSD occurring as a result of interpersonal violence 74 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Supportedcites [74] 74. Cordero MI, Moser DA, Manini A et al. Effects of interpersonal violence- related post-traumatic stress disorder (PTSD) on mother and child diur- nal cortisol rhythm and cortisol reactivity to a laboratory stressor involv- ing separation. Horm Behav 2017;90:15-24. source
The Abstract identifies the toddlers as 12–48 months old and reports that children of mothers with interpersonal violence-related PTSD showed blunted cortisol reactivity to the laboratory stressor. The Children's cortisol section also reports a blunted stress response, though it describes the children's ages there as 12–42 months. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In another study, maternal exposure to child abuse was associated with smaller intracranial volume, due to differences in cortical gray matter, in newborns examined within two weeks of birth 75 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Partly supportedcites [75] 75. Moog NK, Entringer S, Rasmussen JM et al. Intergenerational effect of ma- ternal exposure to childhood maltreatment on newborn brain anatomy. Biol Psychiatry 2018;83:120-7. sourceExperimental — accuracy not yet measured
The Results (Global brain and tissue volumes; page unavailable) associate maternal childhood maltreatment with smaller newborn intracranial volume, principally reflecting lower cortical gray-matter volume. But the Methods (Procedures; page unavailable) report scans at 5–64 days after birth, with a mean of 26 days—not within two weeks. The exposure measure also included childhood neglect as well as abuse. (LLM, conf=0.93)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“In another study, several measures of GR sensitivity were found to be directionally different in offspring of mothers vs. fathers with PTSD 63 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Supportedcites [63] 63. Lehrner A, Bierer LM, Passarelli V et al. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors. Psy- choneuroendocrinology 2014;40:213-20. source
The Results report lower IC50-DEX, indicating greater glucocorticoid sensitivity, in offspring with maternal PTSD than in those with paternal PTSD alone. The Discussion says maternal and paternal PTSD effects were distinguishable and sometimes in opposing directions across three measures of HPA-axis regulation. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
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In the paper
“The increased prevalence of PTSD in Holocaust offspring in response to their own traumatic exposures was later found to be associated with maternal PTSD in Holocaust survivors 28 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE ORIGIN OF STUDIES OF INTERGENERATIONAL TRAUMA EFFECTS
What the sources say
- Supportedcites [28] 28. Yehuda R, Bell A, Bierer LM et al. Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors. J Psychiatr Res 2008;42:1104-11. source
The Results report a higher prevalence of lifetime PTSD in Holocaust survivors’ offspring than in controls and a specific association between offspring PTSD and maternal PTSD. The Introduction also discusses offspring PTSD in relation to their own trauma histories. The Discussion clarifies that Holocaust-offspring status alone did not increase PTSD risk; maternal PTSD was the relevant association. Page numbers were not available in our copy. (LLM, conf=0.90)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“The effects in adulthood were determined to be directly related to the early postnatal environmental exposures to variations in maternal care, since they were prevented by cross-fostering neonatal rat pups to mothers displaying different behavioral characteristics 81,86,90,91 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > POTENTIAL MECHANISMS FOR OBSERVED BIOLOGICAL EFFECTS IN OFFSPRING OF TRAUMA SURVIVORS
What the sources say
- Not checked — no full text of the sourcecites [81] 81. Liu D, Diorio J, Tannenbaum B et al. Maternal care, hippocampal gluco- corticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science 1997;277:1659-62. source
- Not checked — no full text of the sourcecites [86] 86. Weaver IC, Cervoni N, Champagne FA et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004;7:847-54. source
- Not checked — no full text of the sourcecites [90] 90. Champagne F, Meaney MJ. Like mother, like daughter: evidence for non-genomic transmission of parental behavior and stress responsivity. Prog Brain Res 2001;133:287-302. source
- Supportedcites [91] 91. Meaney MJ, Szyf M. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environ- ment and a fixed genome. Dialogues Clin Neurosci 2005;7:103-23. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In a recent study, grandmaternal stress during pregnancy was associated with genome-wide methylation changes in offspring and grandchildren 154 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
What the sources say
- Partly supportedcites [154] 154. Serpeloni F, Radtke K, de Assis SG et al. Grandmaternal stress during preg- nancy and DNA methylation of the third generation: an epigenome-wide association study. Transl Psychiatry 2017;7:e1202. sourceExperimental — accuracy not yet measured
The Abstract and Discussion report an association between grandmaternal stress during pregnancy and DNA methylation in grandchildren. The Materials and methods section says maternal-generation samples were not part of the present study, so this paper does not establish the claimed association in both offspring and grandchildren. (LLM, conf=0.91)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
- It may state two separate claims as one. 60
- Probably not a substantial claim. 25
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
“Maternal age at Holocaust exposure and maternal PTSD were found to independently influence urinary cortisol levels and cortisol metabolism in adult offspring, with the strongest effects in offspring of mothers who were children during World War II 167”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
What the sources say
- Disputedcites [167] 167. Bader HN, Bierer LM, Lehrner A et al. Maternal age at holocaust exposure and maternal PTSD independently influence urinary cortisol levels in adult offspring. Front Endocrinol 2014;5:103. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 1 partially supported, 1 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Checked by a reasoning model — may be wrong.
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.
It may state two separate claims as one.
- Disputed
Every source the paper cites for this claim was checked and supports it.
In the paper
“Specifically, maternal PTSD was associated with lower urinary cortisol levels as well as greater GR sensitivity as measured by the lysozyme inhibition test (an in vitro measure of that sensitivity in peripheral tissue) as well as the dexamethasone suppression test (DST).”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Supportedcites [63] 63. Lehrner A, Bierer LM, Passarelli V et al. Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors. Psy- choneuroendocrinology 2014;40:213-20. source
The Discussion reports lower urinary cortisol excretion and greater glucocorticoid sensitivity on both the lysozyme suppression test (LST) and dexamethasone suppression test (DST) in offspring associated with maternal PTSD. The cited finding concerns offspring of Holocaust survivors; no page number is provided in our copy. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the 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.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > TRANSLATIONAL STUDIES LINKING EPIGENETIC FINDINGS ASSOCIATED WITH MATERNAL CARE IN ANIMALS TO CHILDHOOD ADVERSITY AND OFFSPRING EFFECTS IN HUMANS
What the sources say
- Supportedcites [127] 127. Yehuda R, Daskalakis NP, Bierer LM et al. Holocaust exposure induced in- tergenerational effects on FKBP5 methylation. Biol Psychiatry 2016;80: 372-80. source
The Abstract reports that FKBP5 methylation at bin 3/site 6 was higher in Holocaust survivors than in controls, but lower in their offspring than in offspring controls. The Discussion likewise describes changes at the same site in opposite directions. (LLM, conf=0.94)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The interaction demonstrated that, in the absence of maternal PTSD, offspring with paternal PTSD showed higher GR promoter methylation, whereas offspring with both maternal and paternal PTSD showed lower methylation of this promoter region.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > TRANSLATIONAL STUDIES LINKING EPIGENETIC FINDINGS ASSOCIATED WITH MATERNAL CARE IN ANIMALS TO CHILDHOOD ADVERSITY AND OFFSPRING EFFECTS IN HUMANS
What the sources say
- Supportedcites [126] 126. Yehuda R, Daskalakis NP, Lehrner A et al. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid recep- tor gene in Holocaust survivor offspring. Am J Psychiatry 2014;171: 872-80. source
The Results section (‘Maternal PTSD, Paternal PTSD and GR-1F promoter methylation’) reports a significant interaction: offspring with paternal PTSD only had higher GR-1F promoter methylation, while those with both maternal and paternal PTSD had lower methylation. This directly matches the claim. (LLM, conf=0.95)
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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It 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
“The first documented study of the GR promoter in humans showed higher methylation of the hippocampal GR 1F promoter in post-mortem tissue of adult suicide victims with a history of childhood abuse, similar to findings in rodent pups raised by mothers who provided low levels of licking and grooming 121,122 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > TRANSLATIONAL STUDIES LINKING EPIGENETIC FINDINGS ASSOCIATED WITH MATERNAL CARE IN ANIMALS TO CHILDHOOD ADVERSITY AND OFFSPRING EFFECTS IN HUMANS
What the sources say
- Partly supportedcites [121] 121. McGowan PO, Sasaki A, D'alessio AC et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009;12:342-8. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [122] 122. Labonte B, Yerko V, Gross J et al. Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biol Psychiatry 2012;72:41-8. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“indicating that maternal mood and offspring HPA axis reactivity may be linked through epigenetic processes and sensitive to fetal developmental stage”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
What the sources say
- Supportedcites [141] 141. Oberlander TF, Weinberg J, Papsdorf M et al. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 2008;3:97-106. source
The Conclusion says newborn NR3C1 methylation may link antenatal maternal mood with altered infant HPA stress reactivity. The Discussion reports associations between maternal mood in the second and third trimesters and methylation at different CpG sites, supporting the qualified point about sensitivity to developmental timing. The indexed copy provides section labels but no page numbers. (LLM, conf=0.88)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Among mice exposed to stress during early, mid and late gestation, male F1 with early gestation prenatal stress exposure demonstrated behavioral indicators of stress responsivity and anhedonia, as well as alterations in GR and corticotrophin-releasing factor (CRF) expression and increased HPA axis responsivity, with corresponding alteration in CRF and nr3c1 gene methylation 159”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > FETOPLACENTAL INTERACTIONS: REGULATION BY SEX OF OFFSPRING
What the sources say
- Supportedcites [159] 159. Mueller BR, Bale TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci 2008;28:9055-65. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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It 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
“In animal models, prenatal stress has been shown to lower expression of 11β-HSD2 mRNA and 11B-HSD2 activity, both of which are associated with increased 11β-HSD2 methylation in the placenta 140 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
What the sources say
- Partly supportedcites [140] 140. Nugent BM, Bale TL. The omniscient placenta: metabolic and epigenetic regulation of fetal programming. Front Neuroendocrinol 2015;39:28-37. sourceExperimental — accuracy not yet measured
Section 6.1 reports that prenatal stress decreases placental 11β-HSD2 mRNA in rats and that reduced expression is associated with increased promoter methylation. It also reports reduced 11β-HSD2 in female mouse placentas, but does not specify reduced enzyme activity or associate an activity measurement with methylation. No page number is available in our copy. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- 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
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
“The gestational stage of the fetus is an important determinant of the impact of prenatal exposures on offspring, indicative of developmentally sensitive windows of fetal development 146,147 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
What the sources say
- Supportedcites [146] 146. Yehuda R, Engel SM, Brand SR et al. Transgenerational effects of posttrau- matic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. J Clin Endocrinol Metab 2005;90:4115-8. source
The Discussion states that effects of stress-related glucocorticoid exposure during pregnancy on offspring are partly dependent on fetal gestational age. It also reports particularly strong cortisol effects among babies whose mothers were exposed in the third trimester, supporting the claim about developmentally sensitive timing. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [147] 147. Glover V, O'connor T, O'Donnell K. Prenatal stress and the programming of the HPA axis. Neurosci Biobehav Rev 2010;35:17-22. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
“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 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > TRANSLATIONAL STUDIES LINKING EPIGENETIC FINDINGS ASSOCIATED WITH MATERNAL CARE IN ANIMALS TO CHILDHOOD ADVERSITY AND OFFSPRING EFFECTS IN HUMANS
What the sources say
- Partly supportedcites [127] 127. Yehuda R, Daskalakis NP, Bierer LM et al. Holocaust exposure induced in- tergenerational effects on FKBP5 methylation. Biol Psychiatry 2016;80: 372-80. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Partly 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
“Because of a phenomenon called imprinting, maternal and paternal genomes are differentially marked and re-programmed, and a small number of regions from the DNA of the parent of origin may remain with DNA methylation intact 173,189,191”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Supportedcites [173] 173. Rando OJ. Daddy issues: paternal effects on phenotype. Cell 2012;151: 702-8. source
The Cytosine methylation section describes different treatment of paternal and maternal methylation after fertilization: most paternal methylation is erased, while maternal methylation is protected. It also says a subset of paternal methylation marks, including marks at some imprinted genes, is maintained. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [189] 189. Lane N, Dean W, Erhardt S et al. Resistance of IAPs to methylation repro- gramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 2003;35:88-93. source
- Not checked — no full text of the sourcecites [191] 191. Buiting K, Groß S, Lich C et al. Epimutations in Prader-Willi and Angel- man syndromes: a molecular study of 136 patients with an imprinting de- fect. Am J Hum Genet 2003;72:571-7. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Supported
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In the paper
“Among the epigenetic mechanisms that have been implicated in paternal transmission of stress effects via sperm are DNA methylation, oxidative damage to sperm DNA, histone modifications, and changes in small noncoding RNA [175][176][177][178][179] , including microRNA 180,181”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Partly supportedcites [175] 175. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 2014;17: 89-96. sourceExperimental — accuracy not yet measured
The Results (page unavailable) report altered sperm DNA methylation after paternal odor-fear conditioning and discuss noncoding RNA as a possible mechanism. They found no difference in the histone modifications tested; the paper does not identify oxidative sperm-DNA damage or microRNA as mechanisms in this experiment. Thus it supports part, but not the full list attributed to it. (LLM, conf=0.88)
- Partly supportedcites [176] 176. Gapp K, Jawaid A, Sarkies P et al. Implication of sperm RNAs in transge- nerational inheritance of the effects of early trauma in mice. Nat Neurosci 2014;17:667-9. sourceExperimental — accuracy not yet measured
The paper’s Abstract reports altered sperm small noncoding RNAs, including microRNAs, after early-life trauma in mice, and sperm-RNA injection reproduced effects in offspring. It mentions DNA methylation and histone modifications only as possible later mechanisms, not as demonstrated mechanisms in this study. Our copy does not support the attributed role of oxidative damage to sperm DNA. (LLM, conf=0.88)
- Partly supportedcites [177] 177. Guerrero-Bosagna C, Weeks S, Skinner MK. Identification of genomic fea- tures in environmentally induced epigenetic transgenerational inherited sperm epimutations. PLoS One 2014;9:e100194. sourceExperimental — accuracy not yet measured
The Abstract and Introduction (pages not provided) describe transgenerational sperm DNA-methylation changes after environmental toxicant exposure; the Introduction also notes a correlation between histone marks and regions where methylation changes occur. The Discussion speculates about altered noncoding-RNA expression, but the paper does not establish paternal transmission of stress effects through oxidative sperm-DNA damage, histone modifications, or sperm microRNA changes. (LLM, conf=0.86)
- Not checked — no full text of the sourcecites [178] 178. Milekic MH, Xin Y, O'Donnell A et al. Age-related sperm DNA methylation changes are transmitted to offspring and associated with abnormal be- havior and dysregulated gene expression. Mol Psychiatry 2015;20:995- 1001. source
- Supportedcites [179] 179. Rodgers AB, Morgan CP, Bronson SL et al. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regu- lation. J Neurosci 2013;33:9003-12. source
The citations to this paper follow “including microRNA,” so the relevant attribution is the microRNA mechanism, not every mechanism in the preceding list. The Discussion reports stress-related changes in sperm microRNA content consistent with altered offspring stress responsivity; the supplied passages do not give page numbers. (LLM, conf=0.93)
- Partly supportedcites [180] 180. Jenkins TG, Carrell DT. The sperm epigenome and potential implications for the developing embryo. Reproduction 2012;143:727-34. sourceExperimental — accuracy not yet measured
The Introduction discusses sperm DNA methylation, histone modifications, and RNA transcripts as aspects of the paternal epigenome that may influence embryonic development. The Conclusions and future directions section discusses environmental effects on sperm epigenetics, but does not establish paternal transmission of stress effects or identify oxidative sperm-DNA damage as a mechanism. The sentence cites other sources specifically for microRNA, so that detail is not assessed against this paper. (LLM, conf=0.85)
- Not checked — no full text of the sourcecites [181] 181. Szyf M. Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med 2015;21:134-44. 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.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“female offspring exposed to prenatal stressors had higher HPA axis reactivity than did similarly exposed males, with differences in placental expression of 11β-HSD enzymes”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > FETOPLACENTAL INTERACTIONS: REGULATION BY SEX OF OFFSPRING
What the sources say
- Supportedcites [163] 163. Carpenter T, Grecian S, Reynolds R. Sex differences in early-life program- ming of the hypothalamic-pituitary-adrenal axis in humans suggest in- creased vulnerability in females: a systematic review. J Dev Orig Health Dis 2017;8:244-55. source
The Abstract states that female offspring exposed to stressors had increased HPA-axis reactivity compared with males and reports changes in placental 11β-HSD enzyme expression. The Discussion describes sex-specific differences in 11β-HSD1 and 11β-HSD2 expression, while noting that not every stressor or reactivity test showed a sex difference. (LLM, conf=0.92)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It 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
“Although all of a female's oocytes are present at birth, they can be affected by environmental exposures, particularly during childhood 165”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
What the sources say
- Partly supportedcites [165] 165. Cortessis VK, Thomas DC, Levine AJ et al. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response rela- tionships. Hum Genet 2012;131:1565-89. sourceExperimental — accuracy not yet measured
The Human studies section (page unavailable) proposes childhood as a period of vulnerability for female oocytes and says environmental insults may potentially disturb their epigenetic state. It does not state that all oocytes are present at birth, and it presents the exposure effect as a possibility rather than an established fact. (LLM, conf=0.86)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In vitro fertilization was also used to implant the F0 sperm into a naïve female.This produced similar behavioral and biological findings in the F1, further pointing to biological inheritance through sperm.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [175] 175. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 2014;17: 89-96. sourceExperimental — accuracy not yet measured
The Results (section “Inheritance of effects in the F2 and IVF-derived generations”) report that IVF using F0 sperm produced F1 offspring with altered olfactory anatomy, supporting the inference of biological inheritance. But the authors explicitly state that they could not perform behavioral analyses on IVF-generated offspring, so the claim that IVF produced similar behavioral findings is unsupported. (LLM, conf=0.93)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Although significant sex differences were noted in endocrine and behavioral measures, there was no interaction between sex and paternal stress in the offspring of those exposed at puberty or adulthood.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Supportedcites [179] 179. Rodgers AB, Morgan CP, Bronson SL et al. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regu- lation. J Neurosci 2013;33:9003-12. source
The Results (Analysis of offspring physiology & behavior; page unavailable) report significant sex differences in corticosterone measures, with no sex-by-paternal-stress interaction. They also report a significant sex difference in light–dark box behavior. The study compared offspring of sires stressed during puberty or adulthood. (LLM, conf=0.90)
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“Early maternal separation resulted in decreased nr3c1 DNA methylation in the hippocampus and sperm cells, as well as poor coping behavior.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [205] 205. Gapp K, Bohacek J, Grossmann J et al. Potential of environmental enrich- ment to prevent transgenerational effects of paternal trauma. Neuropsy- chopharmacology 2016;41:2749-58. sourceExperimental — accuracy not yet measured
The Effects of MSUS and EE on GR Expression and Promoter Methylation section reports decreased GR (nr3c1) methylation in the hippocampus of exposed males and their offspring, and in sperm of exposed males. But the intervention combined maternal separation with unpredictable maternal stress, and the Effects of MSUS on Coping Behaviors in Aversive Conditions section reports more active coping in offspring, not poor coping. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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- 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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“was later found to be associated with reduced sperm count, motility and morphology, and altered sperm microRNA, mitochondria and protein in the smoker parent 201,202”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Partly supportedcites [201] 201. Hamad MF, Shelko N, Kartarius S et al. Impact of cigarette smoking on histone (H2B) to protamine ratio in human spermatozoa and its relation to sperm parameters. Andrology 2014;2:666-77. sourceExperimental — accuracy not yet measured
The Results and Discussion (page numbers unavailable) report lower sperm count and motility in smokers, describe reduced normal morphology, and identify altered sperm nuclear proteins. The paper does not report altered sperm microRNA or mitochondria in smokers, so those parts of the claim are unsupported. (LLM, conf=0.90)
- Partly supportedcites [202] 202. Marczylo EL, Amoako AA, Konje JC et al. Smoking induces differential miRNA expression in human spermatozoa: a potential transgenerational epigenetic concern? Epigenetics 2012;7:432-9. sourceExperimental — accuracy not yet measured
The Discussion reports altered sperm microRNA expression in smokers. But the Study population section reports no significant difference in sperm count, motility, or morphology between smokers and non-smokers. The cited passages do not establish altered sperm mitochondria or protein; the reported Ston1 and TRIM26 changes concern mRNA expression. Page numbers are unavailable in our copy. (LLM, conf=0.90)
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.
- Partly 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
“Changes in DNA methylation were observed in sperm from men with alcohol or opioid dependence 199,200 , but effects in offspring were not measured.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [199] 199. Ouko LA, Shantikumar K, Knezovich J et al. Effect of alcohol consumption on CpG methylation in the differentially methylated regions of H19 and IG-DMR in male gametes -Implications for fetal alcohol spectrum dis- orders. Alcohol Clin Exp Res 2009;33:1615-27. source
- Supportedcites [200] 200. Chorbov VM, Todorov AA, Lynskey MT et al. Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opi- oid addicts. J Opioid Manag 2011;7:258. source
The Results report significantly increased sperm-DNA methylation at one OPRM1 CpG site in opioid-dependent men, while the overall sperm-DNA difference was not significant. The Discussion treats effects in offspring as a possibility rather than a measured outcome. This source supports the opioid portion of the sentence; the alcohol portion is not attributed to it alone because the sentence cites two sources. (LLM, conf=0.90)
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.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“These mice (F0) demon-strated behavioral changes in response to the stressor, and also changes in several specific sperm microRNA.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [179] 179. Rodgers AB, Morgan CP, Bronson SL et al. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regu- lation. J Neurosci 2013;33:9003-12. sourceExperimental — accuracy not yet measured
The Results section, “Analysis of sperm miR environment” (page unavailable), reports significant increases in nine specific sperm microRNAs in stressed males. The paper does not report behavioral changes in those F0 males in response to the stressors; its behavioral tests concern their offspring. (LLM, conf=0.88)
plaincorrelationaln = 2- 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
Every source the paper cites for this claim was checked and supports it.
In the paper
“in a social defeat model of stress, male and female F1 mice exhibited altered behaviors, and male F1 had a broader range of affected behaviors 204”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Supportedcites [204] 204. Dietz DM, Laplant Q, Watts EL et al. Paternal transmission of stress- induced pathologies. Biol Psychiatry 2011;70:408-14. source
The Results (page not provided) report altered behavior in offspring of both sexes, including changes in the elevated plus maze and forced swim tests. They also report an altered response to novelty in male but not female offspring, consistent with a broader range of affected behaviors in males; the Discussion describes the male phenotype as more robust. (LLM, conf=0.91)
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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, F3 offspring of these animals continued to show phenotypic differences, indicating conservation of stress effects through sperm.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [176] 176. Gapp K, Jawaid A, Sarkies P et al. Implication of sperm RNAs in transge- nerational inheritance of the effects of early trauma in mice. Nat Neurosci 2014;17:667-9. sourceExperimental — accuracy not yet measured
The paper states that F3 MSUS mice had behavioral symptoms similar to F1 and F2 mice (passage [3], section labeled Abstract; page unavailable). It does not establish that sperm carried the effects into F3: it reports normal sperm miRNA levels in F2 males and proposes other epigenetic marks as a possible means of further transmission. (LLM, conf=0.85)
hedgeddirect- 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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Research on possible intergenerational transmission of stress effects through epigenetic marks in sperm has been conducted in rodents, and includes preconception exposures at various developmental stages to stressful and adverse social experiences 149,175,176,179,181,203,204”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Supportedcites [149] 149. Bale TL. Lifetime stress experience: transgenerational epigenetics and germ cell programming. Dialogues Clin Neurosci 2014;16:297. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [175] 175. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 2014;17: 89-96. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Supportedcites [176] 176. Gapp K, Jawaid A, Sarkies P et al. Implication of sperm RNAs in transge- nerational inheritance of the effects of early trauma in mice. Nat Neurosci 2014;17:667-9. source
Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
hedged- 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.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“However, these results were not observed when offspring were generated by in vitro fertilization, implicating behavioral, rather than germ cell epigenetic, influence.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [204] 204. Dietz DM, Laplant Q, Watts EL et al. Paternal transmission of stress- induced pathologies. Biol Psychiatry 2011;70:408-14. sourceExperimental — accuracy not yet measured
The Results report that most behavioral differences seen after natural breeding were absent in IVF offspring, and the Discussion interprets this as suggesting that most transmission occurs through behavioral mechanisms. But the Results also report a small, significant IVF effect in the forced swim test, and the Discussion allows a limited epigenetic role. The claim overstates the finding by saying the results were not observed with IVF and contrasting behavioral with germ-cell epigenetic influence without that qualification. Page numbers were not supplied in our copy. (LLM, conf=0.88)
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.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The odorant acetophenone paired with an electric shock resulted in behavioral sensitivity in the fear conditioned mice, with an accompanying change in DNA methylation in brain and sperm of the M71 receptor, which is involved in sensing acetophenone.An increased size in the M71 specific glomeruli in the olfactory epithelium and bulb was also observed 175”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [175] 175. Dias BG, Ressler KJ. Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 2014;17: 89-96. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
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
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“early life stress, modeled by unpredictable maternal separation and maternal stress, led to depressive-like behavioral patterns upon exposure to novel environments and changes in sncRNAs in F1 sperm.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [176] 176. Gapp K, Jawaid A, Sarkies P et al. Implication of sperm RNAs in transge- nerational inheritance of the effects of early trauma in mice. Nat Neurosci 2014;17:667-9. sourceExperimental — accuracy not yet measured
The paper reports that F1 mice exposed to unpredictable maternal separation and maternal stress showed depressive-like behavior on the forced swim test, and that several sncRNAs changed in F1 sperm. It does not describe the response to an unfamiliar space on the elevated plus maze as depressive-like; it interprets that result as reduced avoidance and fear (behavioral-results passage [1]; sperm-RNA passage [3], both labeled Abstract in our copy). (LLM, conf=0.83)
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.
It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Males were bred with naïve females and produced offspring with blunted HPA axis responsivity as well as changes in transcription of GR genes in the paraventricular nucleus 179”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
What the sources say
- Partly supportedcites [179] 179. Rodgers AB, Morgan CP, Bronson SL et al. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regu- lation. J Neurosci 2013;33:9003-12. sourceExperimental — accuracy not yet measured
The Breeding Scheme (Materials & Methods) says the males were bred with naïve females, and the Abstract reports reduced HPA stress responsivity in their offspring. The Discussion reports enriched expression of glucocorticoid receptor (GR)-responsive genes in the paraventricular nucleus, not a demonstrated change in transcription of GR genes themselves; the Brain Gene Expression Analysis (Results) says no single gene met its significance criteria. (LLM, conf=0.85)
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.
It may state two separate claims as one.
- Partly supported
In the paper
“The studies described in these reports either failed to find effects in Holocaust offspring, corroborated earlier clinical descriptions, attempted to restrict the observations of damaging effects to a subgroup, or pointed to serious methodological challenges in attempting to address this question empirically [11][12][13] .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE ORIGIN OF STUDIES OF INTERGENERATIONAL TRAUMA EFFECTS
What the sources say
- Not matchedcites [11][12][13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
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
“While some aspects of intergenerational trauma effects remain contested, discussions about whether there are clinically observable intergenerational effects in offspring have become less contentious in the last several years, with the increasing recognition of the universality of this phenomenon.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE ORIGIN OF STUDIES OF INTERGENERATIONAL TRAUMA EFFECTS
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no 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
“At the current time, the idea that epigenetic mechanisms underlie clinical observations in offspring of trauma survivors represents a hypothesis to be tested.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence.
In the paper
“In adulthood, the handled rats had altered basal and stress-induced corticosterone levels as well as higher GR sensitivity on the low-dose DST and greater GR number in the hippocampus [77][78][79] .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > POTENTIAL MECHANISMS FOR OBSERVED BIOLOGICAL EFFECTS IN OFFSPRING OF TRAUMA SURVIVORS
What the sources say
- Not matchedcites [77][78][79]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
In the paper
“Although PTSD was found to occur in association with paternal PTSD in a study of Australian Vietnam Veterans and their offspring 29 , the contribution of potential maternal symptoms, even through secondary traumatization, was not assessed.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE ORIGIN OF STUDIES OF INTERGENERATIONAL TRAUMA EFFECTS
What the sources say
- Not checked — no full text of the sourcecites [29] 29. O'Toole BI, Burton MJ, Rothwell A et al. Intergenerational transmission of post-traumatic stress disorder in Australian Vietnam veterans' families. Acta Psychiatr Scand 2017;135:363-72. 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
“Finally, there had been directionally interesting findings of low cortisol and increased glucocorticoid receptor (GR) sensitivity in Holocaust survivors and other trauma exposed individuals with PTSD, suggesting that the experience of trauma might leave long-lasting biological signatures in stress-related biology that could be a catalyst for longer-term adaptations 55 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Not checked — no full text of the sourcecites [55] 55. Yehuda R, Kahana B, Binder-Brynes K et al. Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry 1995;152:982-6. 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.
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
“There is now converging evidence supporting the idea that offspring are affected by parental trauma exposures occurring before their birth, and possibly even prior to their conception.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > Abstract
hedgeddirect- 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
“Furthermore, dysregulation of stress neurocircuitry is a fundamental feature of mood and anxiety disorders [52][53][54] , including PTSD, found to be prevalent in offspring.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > THE INTRODUCTION OF BIOLOGICAL RESEARCH INTO THE STUDY OF INTERGENERATIONAL EFFECTS OF TRAUMA
What the sources say
- Not matchedcites [52][53][54]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
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
“By 22 weeks of gestation, the fetal HPA axis is developed and functioning, although it continues to be sensitive to environmental influence 137,138 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
What the sources say
- Not checked — no full text of the sourcecites [137] 137. Challis JR, Sloboda D, Matthews SG et al. The fetal placental hypothalamic- pituitary-adrenal (HPA) axis, parturition and post natal health. Mol Cell Endocrinol 2001;185:135-44. source
- Not checked — no full text of the sourcecites [138] 138. Mastorakos G, Ilias I. Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci 2003;997:136-49. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“There may also be different effects on offspring, as well mechanisms underlying these effects, depending on the history of trauma exposure and/or psychiatric symptoms prior to pregnancy.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“The intrauterine environment presents a developmentally potent context 95 , mechanistically distinct from postnatal parenting or family environment, through which maternal trauma or stressful experiences may influence fetal epigenetic programming of the HPA axis 136 .”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
What the sources say
- Not checked — no full text of the sourcecites [95] 95. Seckl JR, Meaney MJ. Glucocorticoid "programming" and PTSD risk. Ann N Y Acad Sci 2006;1071:351-78. source
- Not checked — no full text of the sourcecites [136] 136. Sosnowski DW, Booth C, York TP et al. Maternal prenatal stress and infant DNA methylation: a systematic review. Dev Psychobiol 2018;60:127-39. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Given the directionality of these findings, which is consistent with elevated cortisol levels, it may be that exposures in mothers which originate during pregnancy result in directionally different epigenetic alterations from those observed in offspring where the maternal (or paternal) trauma occurred prior to conception.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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In the paper
“However, the limited data suggesting an association of an epigenetic alteration with maternal age at trauma exposure imply potential contributions of both in utero effects and possibly preconception epigenetic changes to gametes.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
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In the paper
“paternal exposure to preconception stress at any stage of development might impact gametes but, as with females, there may be critical periods of vulnerability to insult.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Contrary to initial understanding, it is now believed that some epigenetic changes in germ cells may survive the nearly global erasure of DNA methylation that occurs before implantation of the embryo, or associate with other epigenetic mechanisms 188,189”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [188] 188. Chong S, Whitelaw E. Epigenetic germline inheritance. Curr Opin Genet Dev 2004;14:692-6. source
- Not checked — no full text of the sourcecites [189] 189. Lane N, Dean W, Erhardt S et al. Resistance of IAPs to methylation repro- gramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 2003;35:88-93. source
hedgedconditional- 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
“Germ cells in both females and males can be affected by trauma exposure, but the critical periods for affecting oocytes and sperm may differ.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Oocytes remain in a haploid de-methylated state until puberty, and are therefore vulnerable to environmental perturbations 166”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
What the sources say
- Not checked — no full text of the sourcecites [166] 166. Faulk C, Dolinoy DC. Timing is everything: the when and how of environ- mentally induced changes in the epigenome of animals. Epigenetics 2011;6:791-7. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In an unpublished study, earlier age of maternal Holocaust exposure was also associated with lower FKBP5 methylation at intron 7 in offspring.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
plaincorrelational- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“To date, there are no known studies that have directly examined transgenerational effects mediated through sperm in humans.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
hedged- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“DNA methylation marks are re-established following their erasure, allowing developmental processes, including cell differentiation, to occur 190”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [190] 190. Reik W, Dean W, Walter J. Epigenetic reprogramming in mammalian de- velopment. Science 2001;293:1089-93. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Accordingly, the nature of the effects may differ in oocytes and sperm in relation to trauma exposure.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“These effects were observed only when limited food access occurred prior to puberty, supporting the hypothesis that the transmission occurred through epigenetic programming of gametes and may be mediated by the X and Y sex chromosomes 181,195”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [181] 181. Szyf M. Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med 2015;21:134-44. source
- Not checked — no full text of the sourcecites [195] 195. Pembrey ME, Bygren LO, Kaati G et al. Sex-specific, male-line transgen- erational responses in humans. Eur J Hum Genet 2006;14:159. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Unlike oocytes, which are formed in females prior to birth, spermatogenesis in males is initiated in the testes at puberty and continues throughout the lifespan 174”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [174] 174. Desai N, Ludgin J, Sharma R et al. Female and male gametogenesis. In: Falcone T, Hurd WW (eds). Clinical reproductive medicine and surgery. New York: Springer, 2017:43-62. source
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The unknown variance associated with unmeasured stress in prior generations and its relevance to any maternal exposures is simply not known and creates a difficulty in ascertaining mechanisms.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. 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
“it is methodologically extremely difficult to separate out effects in an oocyte from effects of the fetoplacental environment”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > INTERGENERATIONAL EFFECTS OF PRECONCEPTION MATERNAL TRAUMA
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no 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
“studies examining offspring in close proximity to birth may be particularly informative regarding offspring biology”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > FETOPLACENTAL INTERACTIONS: REGULATION BY SEX OF OFFSPRING
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
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Probably not a substantial claim. It may be too vague to check against evidence. 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
“They will be less informative with respect to offspring phenotype as it is expressed later in life.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > FETOPLACENTAL INTERACTIONS: REGULATION BY SEX OF OFFSPRING
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
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
“Restricted nutritional intake in paternal grandfathers affected mortality rates in grandsons only, whereas paternal grandmother access to food was associated with mortality of granddaughters.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [181] 181. Szyf M. Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med 2015;21:134-44. source
- Not checked — no full text of the sourcecites [195] 195. Pembrey ME, Bygren LO, Kaati G et al. Sex-specific, male-line transgen- erational responses in humans. Eur J Hum Genet 2006;14:159. 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.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the exact nature of the mechanisms involved in transmission through gametes continues to remain obscure”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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
“Scientific studies are rapidly identifying epigenetic mechanisms to explain how an environmental exposure may lead to an enduring change in the function of DNA that can be passed to future generations.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no 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
“In the context of offspring born to two trauma survivors, these two modes of epigenetic influences are likely to interact, and it is indeed very difficult to parse out the many potential contributions to offspring phenotype, not to mention those related to the offspring's own experiences through childhood, adolescence and adulthood.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“The assertion that an effect is truly transgenerational requires ruling out direct exposure of offspring as a causal mechanism.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
In the paper
“a reanalysis of these data showed that the child's early life circumstances were also relevant to findings from father to son but, when childhood factors in sons were controlled in statistical analyses, the transmission effects through the male line were strengthened 194”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [194] 194. Kaati G, Bygren LO, Pembrey M et al. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 2007; 15:784. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“In males, F1 may be influenced via the germ line of the exposed F0 father, but since sperm is not generated in the fetus (as ova are in females), transmission of trauma-associated traits to F2 would be considered transgenerational transmission.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Overeating in paternal grandfathers was associated with increased risk for diabetes in grandchildren, whereas limited food availability in fathers was associated with protection from cardiovascular death in sons.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
What the sources say
- Not checked — no full text of the sourcecites [194] 194. Kaati G, Bygren LO, Pembrey M et al. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 2007; 15:784. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings indicate that stress-induced changes to germ cells are not immutable and can be reversed by alternative environmental perturbations that are directed at stimulating plasticity.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the absence of studies examining the effects of trauma through the male germ line in humans, the above findings demonstrate that a wide range of environmental exposures, not only exposure to extreme trauma, can have biological and behavioral effects that persist in one or more generations.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRECONCEPTION PATERNAL EFFECTS AND OFFSPRING PHENOTYPE: PROOF OF CONCEPT FOR THE ROLE OF SPERM
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These changes are likely to be mediated primarily by maternal trauma-related symptoms, but may be affected by multiple inputs, including paternal trauma-related effects.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: unclear — It is unclear why the paper says 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
“Nonetheless, the findings in animal models implicating epigenetic mechanisms in the transmission of stress effects through germ cells have created much excitement for the possibility that similar mechanisms might be operating in humans.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
hedged- 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.
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Probably not a substantial claim.
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
“This series of studies provides a clear demonstration of an epigenetically mediated transgenerational biological inheritance through sperm of a behavioral trait and corresponding neuroanatomical brain changes that persist for two generations.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
boosteddirect- 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.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Research on epigenetic inheritance of effects of trauma faces many scientific and methodological complexities, not to mention conceptual issues regarding interpretation of transmitted effects.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim. It may be too vague to check against evidence. 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
“Even potentially heritable changes can be modified, because environments change.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence.
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
“Thus, for females, traits must be observed in F3 females to be considered transgenerational, because the F1 female offspring is exposed to the stressor during gestation through the intrauterine environment.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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Probably not a substantial claim.
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 second are the effects of a preconception parental trauma that remain in the germ cell and following conception, affecting the offspring's development in utero and subsequent postnatal phenotype.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no 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
“The state of the science in relation to human offspring at present is that, whereas some neuroendocrine and epigenetic alterations have been documented in connection with maternal and paternal trauma exposure and PTSD, studies have not yet conclusively demonstrated epigenetic transmission of trauma effects in humans.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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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
“Epigenetic mechanisms have been favored over genetic explanations (or gene-environment interactions) of intergenerational effects in part because of their potential to explain the phenotypic differences in offspring associated with maternal vs. paternal trauma exposure.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no 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
“At the present time, the field has not sufficiently grappled with the meaning of the intergenerational transmission of trauma effects for the offspring.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no 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
“However, there is much diversity in effects, and opportunities for modifying even strong effects of non-coding RNAs, chromatin, and DNA methylation.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check 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. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. 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
“These findings confirmed that early or later life exposures in the male mouse can affect germ cell microRNA, and are sufficient to result in a similar phenotype in the subsequent generation, again confirming the transmission through sperm in an independent animal model.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > STUDIES OF INTER-AND TRANSGENERATIONAL STRESS IN MALE RODENTS
boosteddirect- 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
“Ultimately, the potential utility, and possible stability, of an environmentally induced trait transmitted to an offspring will depend on the offspring's environmental context.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plainconditional- 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.
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 principle of epigenetic plasticity implies that changes to the epigenome might reset when the environmental insults are no longer present, or when we have changed sufficiently to address environmental challenges in a new way.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > 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: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no 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
“It is the ability to flexibly respond to environmental stimuli that is fundamentally adaptive and the basis of human resilience.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
The paper relies on this without support.
Peripheral blood methylation findings reflect epigenetic processes relevant to brain or stress biology.
“Following this observation in post-mortem brain tissue, higher GR promoter methylation in circulating leukocytes of healthy adults was also found to be associated with disrupted, inadequate, or abusive parenting [123][124][125] .”
“The first documented study of the GR promoter in humans showed higher methylation of the hippocampal GR 1F promoter in post-mortem tissue of adult suicide victims with a history of childhood abuse, similar to findings in rodent pups raised by mothers who provided low levels of licking and grooming 121,122 .”
The paper relies on this without support.
Parental PTSD status is a valid indicator of the relevant parental trauma exposure for offspring effects.
“Subsequent investigations documented that maternal and paternal PTSD were associated with different biological outcomes.”
“This possibility is consistent with clinical, neuroendocrine and epigenetic findings, in which maternal and paternal PTSD predicted different psychiatric and biological outcomes in offspring 28,126 .”
The paper relies on this without support.
Preconception trauma exposure, prenatal stress, and postnatal parenting are unlikely to be independent in humans.
“Preconception trauma exposure, prenatal stress, and postnatal parenting are unlikely to be independent in humans, adding to the complexity of drawing conclusions about specific influences on offspring.”
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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
“This transgenerational effect has been attributed to the fact that prenatal exposure directly impacts both the fetus and the fetal germ cells, thus directly exposing the third generation.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > CONCLUSIONS AND FUTURE DIRECTIONS
“The assertion that an effect is truly transgenerational requires ruling out direct exposure of offspring as a causal mechanism.Thus, for females, traits must be observed in F3 females to be considered transgenerational”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
“Studies of preconception exposure to trauma without specific consideration of gestational age of exposure have also been published.”
§ Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms > PRENATAL MATERNAL CONTRIBUTIONS TO OFFSPRING VIA FETOPLACENTAL INTERACTIONS
“Higher levels of NR3C1 methylation were observed in offspring aged 10-19 of mothers who experienced intimate partner violence during, but not prior to or following, pregnancy 155 .”
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- 10.1176/ajp.155.9.1163 · DOI · Paper page
- DeGruy J, 2005, Post traumatic slave syndrome: America's legacy of enduring injury and healing
Cited by
Sorted by citations
Fiorillo, A., Sampogna, G., Giallonardo, V., Vecchio, V. D., Luciano, M., Albert, U., Carmassi, C., Carrà, G., Cirulli, F., Dell’Osso, B. M., et al. (2020) · European Psychiatry · doi:10.1192/j.eurpsy.2020.89 · Cited by 382
Maternal prenatal stress phenotypes associate with fetal neurodevelopment and birth outcomes
Walsh, K., McCormack, C. A., Webster, R., Pinto, A., Lee, S., Feng, T., Krakovsky, H. S., O’Grady, S. M., Tycko, B., Champagne, F. A., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1905890116 · Cited by 273
Giallonardo, V., Sampogna, G., Del Vecchio, V., Luciano, M., Albert, U., Carmassi, C., Carrà, G., Cirulli, F., Dell’Osso, B., Nanni, M. G., et al. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00533 · Cited by 250
Association of Adverse Childhood Experiences With Cardiovascular Disease Later in Life
Godoy, L. C., Frankfurter, C., Cooper, M., Lay, C. L., Maunder, R., & Farkouh, M. E. (2020) · JAMA Cardiology · doi:10.1001/jamacardio.2020.6050 · Cited by 247
Treatment of Posttraumatic Stress Disorder: A State-of-the-art Review
Burback, L., Brémault‐Phillips, S., Nijdam, M. J., McFARLANE, A. C., & Vermetten, E. H. G. J. M. (2023) · Current Neuropharmacology · doi:10.2174/1570159x21666230428091433 · Cited by 251
Metadata
- Authors
- Yehuda, R., & Lehrner, A.
- Affiliations
- James J. Peters VA Medical Center (US)
- Venue
- World Psychiatry
- Publisher
- Wiley
- Published
- 2018-09-07
- Volume
- 17
- Issue
- 3
- Pages
- 243-257
- ISSN
- 1723-8617 (ISSN-L)
- 2051-5545
- PMC
- PMC6127768
- OpenAlex
- W2891168202
- Cited by
- 730
- References
- 210
- Citations by year
- 2026: 140 · 2025: 135 · 2024: 94 · 2023: 87 · 2022: 114 · 2021: 61 · 2020: 71 · 2019: 23 · 2018: 3
- FWCI
- 43.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- World Psychiatry (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- intergenerational trauma, epigenetics, developmental programming, maternal care, prenatal stress, maternal trauma, sex differences, animal models
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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