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Cited by 43Child Abuse and TraumaTelomeres, Telomerase, and SenescenceChild and Adolescent Psychosocial and Emotional Development

Telomere Length and Psychopathology: Specificity and Direction of Effects Within the Bucharest Early Intervention Project

Open access
Wade, Mark, Fox, Nathan A., Zeanah, Charles H., Nelson, Charles A., Drury, Stacy S.·2020·Journal of the American Academy of Child & Adolescent Psychiatry
DOI 10.1016/j.jaac.2019.02.013PMC PMC8056885
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Abstract

Objective: Telomere length has been linked to several psychiatric conditions in children and adults. Telomere shortening is accelerated by early adversity, including maltreatment and psychosocial deprivation. These experiences also increase the risk of psychopathology in many domains. Two fundamental issues remain unresolved. The first concerns the specificity of the relations between TL and different dimensions of psychopathology; and the second relates to the direction of association between TL and psychopathology. Method: This study addresses these shortcomings in a two-fold manner. First, we examined the association between TL and statistically-independent general, internalizing, and externalizing psychopathology factors to determine the specificity of this relation. Second, we used a two-wave longitudinal cross-lagged model to explicitly examine the direction of the relation between telomere length and each psychopathology factor. Data were drawn from the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of severe psychosocial deprivation on child health and development (N = 195). At age 8–10 and 12–14, buccal DNA were collected and teachers and/or caregivers reported on different domains of psychopathology. Results: Longitudinal path analyses revealed that shorter telomere length was specifically associated with higher internalizing psychopathology at age 8–10. In contrast, at age 12–14, shorter telomere length was associated with higher general psychopathology. Most telling, internalizing psychopathology at age 8–10 predicted shorter telomere length at age 12–14, with no reciprocal effects. Conclusion: Results suggest that telomere erosion may be a consequence of distress-related psychopathology rather than a selection mechanism for later psychiatric problems. Trial Registration: Clinicaltrials.gov Identifier: NCT00747396

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Crossref · 10.1016/j.jaac.2019.02.013

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 49 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Higher internalizing psychopathology at ages 8-10 predicted shorter telomere length at ages 12-14 after controlling for telomere length at ages 8-10.

    “internalizing psychopathology at age 8–10 predicted shorter telomere length at age 12–14, with no reciprocal effects.”
    • Also stated in: § Association between telomere length and psychopathology · plain
      “higher internalizing psychopathology at age 8–10 predicted shorter telomere length at age 12–14 after controlling for telomere length at age 8–10.”
    Quote in the paperSubstantial claim
  • Findingown data

    General and externalizing psychopathology at ages 8-10 did not predict telomere length at ages 12-14.

    “Neither general nor externalizing psychopathology at age 8–10 were associated with telomere length at age 12–14”
    Quote in the paperSubstantial claim
  • Findingown data

    Among female participants, longer duration of institutional care at baseline and 54 months was associated with shorter telomere length at ages 12-14.

    “In female participants, greater duration of institutional care at baseline and 54 months was associated with shorter telomere length at age 12–14.”
    Quote in the paperSubstantial claim
  • Findingown data

    There were no observable differences between ever-institutionalized and never-institutionalized children in the paths linking psychopathology and telomere length.

    “there were no observable differences in the paths linking psychopathology and telomere length between EIG and NIG children”
    Quote in the paperSubstantial claim
  • Findingown data

    Ever-institutionalized children had significantly higher general psychopathology at ages 8-10 than never-institutionalized children.

    “EIG children had significantly higher general psychopathology at age 8–10 than NIG”
    Quote in the paperSubstantial claim
  • May combine two claims. 20
  • The quote only partly states this claim. 1
  • Classified as probably not a substantial claim. 31

  • May combine two claims.

    Findingown data

    At ages 8-10, children with shorter telomere length had higher internalizing psychopathology, and telomere length was not associated with general or externalizing psychopathology at that age.

    “Longitudinal path analyses revealed that shorter telomere length was specifically associated with higher internalizing psychopathology at age 8–10.”
    • Also stated in: § Association between telomere length and psychopathology · plain
      “In terms of within-time associations, shorter telomere length at age 8–10 was significantly associated with higher internalizing problems, but was unrelated to general or externalizing psychopathology.”
    • Also stated in: § Discussion · boosted
      “We provide the first evidence that internalizing problems are associated with shorter telomere length in late childhood (age 8–10)”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Findingown data

    Telomere length did not predict later psychopathology; no reciprocal effects were found.

    “with no reciprocal effects”
    • Also stated in: § Association between telomere length and psychopathology · plain
      “no reciprocal effects of telomere length on psychopathology emerged.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At ages 12-14, shorter telomere length was associated with higher general psychopathology, but not with internalizing or externalizing psychopathology.

    “In contrast, at age 12–14, shorter telomere length was associated with higher general psychopathology.”
    • Also stated in: § Association between telomere length and psychopathology · plain
      “On the other hand, shorter telomere length at age 12–14 was associated with higher general, but not internalizing or externalizing, psychopathology.”
    • Also stated in: § Discussion · plain
      “yet in early adolescence (age 12–14), shorter telomeres are associated with higher general psychopathology.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Among children in the care-as-usual group, greater exposure to institutional care at 54 months, 8 years, and 12 years was associated with shorter telomere length at ages 12-14; this association was not found in the foster care group.

    “greater exposure to institutional care at 54 months, 8 years, and 12 years was associated with shorter telomere length at age 12–14 among CAUG, but not FCG”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    General psychopathology was relatively stable over time regardless of institutional status, while internalizing and externalizing showed little stability after accounting for general factor stability.

    “there was relative stability in general psychopathology over time, regardless of institutional status, but little stability in internalizing or externalizing after accounting for stability in the general factor.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Telomere erosion may result from distress-related psychopathology rather than acting as a selection mechanism for later psychiatric problems.

    “Results suggest that telomere erosion may be a consequence of distress-related psychopathology rather than a selection mechanism for later psychiatric problems.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    There was one direct association between institutionalization status and relational aggression at age 8 only, which generally supported invariance across groups.

    “There was a single direct association between institutionalization status and relational aggression at age 8 only, generally supporting invariance across groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Institutionally reared children with profound psychosocial deprivation have shorter telomeres as a function of time spent in institutions and show accelerated telomere shortening from age 6 to 15 compared with never-institutionalized children.

    “institutionally-reared children raised under conditions of profound psychosocial deprivation have been shown to have shorter telomeres as a function of time spent in institutions,9 as well as accelerated telomere shortening from age 6 to 15 compared to never-institutionalized children.10”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [9] Drury, 2012, Telomere length and early severe social deprivation: linking early adversity and cellular aging, Mol Psychiatry source

      Not checked in the free run.

    • cites [10] Humphreys, 2016, Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level, Psychiatry Res source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Environmental stress, including perceived psychological distress, is associated with shorter telomere length in human studies, including meta-analyses.

    “Environmental stress, including perceived psychological distress, has been associated with shorter telomere length in a number of human studies, including meta analyses.3–5”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [3] Choi, 2008, Reduced telomerase activity in human T lymphocytes exposed to cortisol, Brain Behav Immun source

      Not checked in the free run.

    • cites [4] Mathur, 2016, Perceived stress and telomere length: a systematic review, meta-analysis, and methodologic considerations for advancing the field, Brain Behav Immun source

      Not checked in the free run.

    • cites [5] Epel, 2004, Accelerated telomere shortening in response to life stress, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The link between duration of institutionalization and telomere length varied by sex and age of assessment, rather than there being direct associations between institutionalization group and telomere length.

    “Thus, there are associations between duration of institutionalization and telomere length that vary based on sex and age of assessment rather than direct associations between institutionalization group and telomere length.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    Cross-lagged models test reciprocal relations between constructs after controlling within-time covariance and cross-time stability, bringing researchers closer to causal effects.

    “Cross-lagged models test for reciprocal relations between constructs once within-time covariance terms and cross-time stability coefficients are controlled, leading researchers closer to establishing causal effects.27”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [27] Burkholder, 2003, An illustration of a longitudinal cross-lagged design for larger structural equation models, Struct Eq Model source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Measurement invariance over time for the psychopathology factors was established in a previous investigation.

    “This previous study established measurement invariance on these factors over time.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Wade, 2018, Effect of foster care intervention on trajectories of general and specific psychopathology among children with histories of institutional rearing: a randomized clinical trial., JAMA Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Full-information maximum likelihood outperforms other missing-data methods in parameter bias, model convergence, and model fit.

    “FIML has been shown to outperform other methods for handling missing data, including listwise deletion, pairwise deletion, and mean substitution in terms of parameter bias, model convergence, and model fit.34”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Enders, 2001, The relative performance of full information maximum likelihood estimation for missing data in structural equation models, Struct Eq Model source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A recent comprehensive review supports the hypothesis that telomere length is most strongly related to stress-related psychiatric disorders and indexes both adversity exposure and future health risk.

    “A recent comprehensive review provides support for the hypothesis that telomere length is most strongly related to stress-related psychiatric disorders and indexes both adversity exposure and future health risk.17”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Epel, 2018, Stress, telomeres, and psychopathology: toward a deeper understanding of a triad of early aging, Ann Rev Clin Psychol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted).

    Premisecitation

    The behavioral causation model proposes that psychopathology leads to telomere erosion over time.

    “The first suggests that psychopathology leads to telomere erosion over time (“behavioral causation”).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Bateson, 2018, Why are there associations between telomere length and behaviour?, Phil Trans R Soc Lond B Biol Sci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The externalizing factor indexes approach-related traits such as sensation-seeking and surgency.

    “while the internalizing factor captures elements of fear and distress, and the externalizing factor indexes approach-related traits such as sensation-seeking and surgency.22,23”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Forbes, 2017, Unique associations between childhood temperament characteristics and subsequent psychopathology symptom trajectories from childhood to early adolescence, J Abnorm Child Psychol source

      Not checked in the free run.

    • cites [23] Olino, 2014, Testing models of psychopathology in preschool-aged children using a structured interview-based assessment, J Abnorm Child Psychol source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The general psychopathology factor is believed to reflect high negative emotionality and emotion dysregulation that underpin many conditions.

    “The general factor is believed to reflect high negative emotionality and emotion dysregulation that underpins many conditions,21”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [21] Beauchaine, 2015, Heart rate variability as a transdiagnostic biomarker of psychopathology, Int J Psychophysiol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    The latent structure of psychopathology includes shared causal influences and unique liabilities to different psychiatric problems.

    “Recent reports on the latent structure of psychopathology posit both shared causal influences and unique liabilities to different psychiatric problems.18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Caspi, 2014, The p factor: one general psychopathology factor in the structure of psychiatric disorders?, Clin Psychol Sci source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The internalizing factor captures elements of fear and distress.

    “while the internalizing factor captures elements of fear and distress, and the externalizing factor indexes approach-related traits such as sensation-seeking and surgency.22,23”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [22] Forbes, 2017, Unique associations between childhood temperament characteristics and subsequent psychopathology symptom trajectories from childhood to early adolescence, J Abnorm Child Psychol source

      Not checked in the free run.

    • cites [23] Olino, 2014, Testing models of psychopathology in preschool-aged children using a structured interview-based assessment, J Abnorm Child Psychol source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Shorter telomeres are associated with multiple psychiatric conditions, including stress-related disorders, mood disorders, externalizing disorders, and neurodevelopmental disorders.

    “Emerging evidence suggests that shorter telomeres are associated with multiple psychiatric conditions, including stress-related disorders such as PTSD and anxiety, mood disorders including depression and bipolar, externalizing disorders, and neurodevelopmental disorders such as autism.11–16”
    Quote in the paperSubstantial claim0 of 6 sources checked
    • cites [11] Darrow, 2016, The association between psychiatric disorders and telomere length: a meta-analysis involving 14,827 persons, Psychosom Med source

      Not checked in the free run.

    • cites [12] Powell, 2018, Telomere length and bipolar disorder, Neuropsychopharmacology source

      Not checked in the free run.

    • cites [13] Ridout, 2016, Depression and telomere length: a meta-analysis, J Affect Disord source

      Not checked in the free run.

    • cites [14] Nelson, 2015, Shortened telomeres in families with a propensity to autism, J Am Acad Child Adolesc Psychiatry source

      Not checked in the free run.

    • cites [15] Wojcicki, 2015, Telomere length is associated with oppositional defiant behavior and maternal clinical depression in Latino preschool children, Transl Psychiatry source

      Not checked in the free run.

    • cites [16] de Souza Costa, 2015, Telomere length is highly inherited and associated with hyperactivity-impulsivity in children with attention deficit/hyperactivity disorder, Front Mol Neurosci

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The selective adoption model proposes that shorter telomere length predisposes individuals to later psychopathology.

    “This model predicts that shorter telomere length predisposes individuals to later psychopathology.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Bateson, 2018, Why are there associations between telomere length and behaviour?, Phil Trans R Soc Lond B Biol Sci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Stress related to psychopathology is associated with physiological and cellular alterations related to telomere length, such as elevated oxidative stress or inflammation.

    “This model is consistent with the idea that stress related to psychopathology is associated with physiological and cellular alterations related to telomere length, such as elevated oxidative stress or inflammation.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Ng, 2008, Oxidative stress in psychiatric disorders: evidence base and therapeutic implications, Int J Neuropsychopharmacol source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In neural precursor cells, telomere length influences the timing and direction of cellular differentiation.

    “In neural precursor cells, telomere length influences the timing and direction of cellular differentiation, suggesting a role for telomeres in cellular aging, differentiation, and survival.2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Ferrón, 2009, Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis, J Neurosci source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    In Gotlib et al., daughters of depressed mothers who had not developed depression had shorter telomeres than daughters of non-depressed mothers.

    “In their study, the daughters of depressed mothers, who had not developed depression themselves, had shorter telomeres compared to daughters of non-depressed mothers”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [26] Gotlib, 2015, Telomere length and cortisol reactivity in children of depressed mothers, Mol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Healthy daughters of depressed women have shorter telomeres than daughters of never-depressed women, suggesting that telomere shortening antedates and may be a risk factor for depression.

    “Gotlib and colleagues have demonstrated that healthy daughters of depressed women have shorter telomeres compared to daughters of never-depressed woman, suggesting that telomere shortening antedates, and may be a risk factor for, depression.26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Gotlib, 2015, Telomere length and cortisol reactivity in children of depressed mothers, Mol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Erosion of telomeres is accelerated by oxidative stress, which partially accounts for the gap between observed and predicted telomere shortening.

    “Erosion of telomeres is accelerated by processes such as oxidative stress, which partially account for the gap between observed rates of telomere shortening and those predicted by the end-replication problem.2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Ferrón, 2009, Telomere shortening in neural stem cells disrupts neuronal differentiation and neuritogenesis, J Neurosci source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The fastest telomere loss occurs in the earliest years of life.

    “since telomere attrition is greatest during the first years of life,38”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Frenck, 1998, The rate of telomere sequence loss in human leukocytes varies with age, Proc Natl Acad Sci U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Telomeres naturally shorten with each mitotic division because of the end-replication problem of DNA polymerase.

    “Telomeres naturally shorten with each mitotic division due to the “end-replication problem” of DNA polymerase.1”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [1] Chan, 2004, Telomeres and telomerase, Phil Trans R Soc Lond B Biol Sci source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The current study cannot rule out long-term transactional effects between telomere length and psychopathology, including shorter telomeres from increased internalizing psychopathology forecasting later psychopathology risk.

    “the current study cannot rule out long-term transactional effects between telomere length and psychopathology, with shorter telomeres as a function of increased internalizing psychopathology forecasting later risk for psychopathology.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The potential for bias from missing data was minimized by best-practice methods.

    “The potential for bias was minimized by using best-practice methods for handling missing data.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductcitation

    The latent psychopathology factors were successfully reproduced at both time points, and measurement invariance had been previously demonstrated.

    “we were able to successfully reproduce the latent psychopathology factors at both time points and have previously demonstrated measurement invariance.31”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Wade, 2018, Effect of foster care intervention on trajectories of general and specific psychopathology among children with histories of institutional rearing: a randomized clinical trial., JAMA Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Stress reactivity mediated by cortisol is linked to faster telomere shortening.

    “cortisol-mediated stress reactivity is associated with accelerated telomere shortening,26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Gotlib, 2015, Telomere length and cortisol reactivity in children of depressed mothers, Mol Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Buccal swabs may better reflect brain epigenetic processes than blood or saliva because they share ectodermal origin with the neural system.

    “buccal swabs measure telomeres in cells with the same embryologic origin as the neural system, the ectoderm”
    • Also stated in: § Discussion · hedged
      “and therefore may be more reflective of epigenetic processes in the brain than blood or saliva”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Telomeres in buccal cells come from ectodermal tissue, the same embryonic layer as the neural system.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    DNA was not available for all participants at all time points.

    “DNA was not available for all study participants at all time points.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Inflammation and oxidative stress processes have been implicated in the pathophysiology of distress-related psychopathology such as anxiety and depression.

    “These processes have also been implicated in the pathophysiology of distress-related psychopathology (i.e., anxiety and depression).42”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [42] Hovatta, 2010, Oxidative stress in anxiety and comorbid disorders, Neurosci Res source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Shorter telomeres have been linked to higher morbidity and mortality from multiple causes.

    “Since telomere erosion is associated with increased morbidity and mortality from a number of causes,46”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Wolkowitz, 2010, Depression gets old fast: do stress and depression accelerate cell aging?, Depress Anxiety source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Inflammation decreases leukocyte telomere length by increasing leukocyte turnover and accelerating replicative senescence.

    “inflammation has been shown to decrease leukocyte telomere length by increasing leukocyte turnover and accelerating replicative senescence.39”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [39] Aviv, 2004, Telomeres and human aging: facts and fibs, Sci Aging Knowledge Environ source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Oxidative stress can preferentially damage telomeric DNA, disrupt telomerase, and influence epigenetic factors such as methylation and phosphorylation.

    “A related mechanism involves changes in cellular redox potential (e.g., oxidative stress), in which reactive oxygen species preferentially damage DNA at telomeres, disrupt telomerase activity (the enzyme that lengthens telomeres), and/or influence epigenetic factors such as methylation and phosphorylation.40,41”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [40] Ahmed, 2018, Impact of oxidative stress on telomere biology, Differentiation source

      Not checked in the free run.

    • cites [41] von Zglinicki, 2002, Oxidative stress shortens telomeres, Trends Biochem Sci source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Post-hoc bootstrap re-sampling yielded similar but more conservative results, supporting robustness.

    “Post-hoc analyses using bootstrap re-sampling methods yielded similar, though more conservative, results, supporting the robustness of effects.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    Telomere attrition from distress-related psychopathology plausibly contributes to increased premature mortality among people with psychiatric conditions.

    “it is plausible that telomere attrition as a function of distress-related psychopathology contributes to increased rates of premature mortality among individuals with psychiatric conditions.47”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Kiecolt-Glaser, 2016, Psychiatric disorders, morbidity, and mortality: tracing mechanistic pathways to accelerated aging, Psychosom Med source

      Not checked in the free run.

    • Rests on an assumption: Psychiatric disorders often occur alongside age-related medical conditions like diabetes and cardiovascular disease.

  • May combine two claims.

    Premisecitation

    There is no evidence that one biological source is superior for telomere measurement, and telomere length is highly correlated across tissue types.

    “there is no evidence to date that one biological source is superior, and there is also a high correlation in telomere length measured across tissue types.45”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Daniali, 2013, Telomeres shorten at equivalent rates in somatic tissues of adults, Nat Commun source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Missing data may have introduced bias.

    “Fourth, missing data across participants may have introduced bias.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Interventions that reduce stress-related psychopathology effects or target telomere length may improve physical and mental health by attenuating telomere erosion or increasing telomerase activity.

    “Interventions designed to reduce the stress-related effects of psychopathology or target telomere length directly (e.g. exercise, meditation, and antioxidants) may engender positive effects on physical and mental health by attenuating telomere erosion and/or increasing telomerase activity.48–50”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [48] Schutte, 2014, A meta-analytic review of the effects of mindfulness meditation on telomerase activity, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [49] Dimauro, 2017, Regular exercise participation improves genomic stability in diabetic patients: an exploratory study to analyse telomere length and DNA damage, Sci Rep source

      Not checked in the free run.

    • cites [50] Prasad, 2017, Telomere shortening during aging: attenuation by antioxidants and anti-inflammatory agents, Mech Ageing Dev source

      Not checked in the free run.

43 of 43

  • The paper relies on this without support.

    Most previous studies examining the link between telomere length and discrete disorders did not control for other domains of psychopathology.

    “However, in assessing the link between telomere length and discrete disorders, most previous studies failed to control for other domains of psychopathology.”

  • The paper relies on this without support.

    No study in children or adolescents has assessed both telomere length and psychopathology across multiple waves and examined cross-lagged associations.

    “To date, no study in children or adolescents has assessed both telomere length and psychopathology across multiple waves of data collection and examined their cross-lagged associations.”

  • The paper relies on this without support.

    The general psychopathology factor is a latent liability to psychopathology characterized by high negative emotionality and deficits in emotion regulation.

    “Given that the general psychopathology factor is conceptualized as a latent liability to psychopathology that is characterized by high negative emotionality and deficits in emotion regulation”

  • The paper relies on this without support.

    Telomeres in buccal cells come from ectodermal tissue, the same embryonic layer as the neural system.

    “buccal swabs measure telomeres in cells with the same embryologic origin as the neural system, the ectoderm”

  • The paper relies on this without support.

    Psychiatric disorders often occur alongside age-related medical conditions like diabetes and cardiovascular disease.

    “Psychiatric illness frequently co-occurs with age-related medical illnesses such as cardiovascular disease and diabetes.”
5 of 5

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Early neglect can compound normative developmental risks, leading to greater telomere shortening and increased long-term health risks.

    “early neglect can compound these effects, leading to even greater telomere shortening and increased long-term health risks (Wade et al., 2020).”

    From Telomere trajectories from early adolescence to adulthood following early institutionalization: Protective effects of foster care in the Bucharest Early Intervention Project (2026) · cites this paper as Wade et al., 2020

    The Introduction (page not provided) reports that children exposed to profound psychosocial deprivation showed accelerated telomere shortening compared with never-institutionalized children, beyond the natural shortening it describes. The Discussion (page not provided) links telomere erosion to morbidity and mortality, but treats downstream health effects as plausible and in need of further research; it does not establish that early neglect leads to increased long-term health risks. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Cites

Flagged first, then by citations

Research works printed but not linked: 2

  1. Drury, 2012, Telomere length and early severe social deprivation: linking early adversity and cellular aging, Mol Psychiatry, 17, 719, 10.1038/mp.2011.53 · DOI · Paper page
  2. Humphreys, 2016, Accelerated telomere shortening: tracking the lasting impact of early institutional care at the cellular level, Psychiatry Res, 246, 95, 10.1016/j.psychres.2016.09.023 · DOI · Paper page

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Authors
Wade, M., Fox, N. A., Zeanah, C. H., Nelson, C. A., & Drury, S. S.
Affiliations
  • Boston Children's Hospital (US)
  • University of Maryland, College Park (US)
  • Tulane University (US)
Corresponding author
Wade, Mark
ORCID
Venue
Journal of the American Academy of Child & Adolescent Psychiatry
Publisher
Elsevier BV
Published
2020-01
Volume
59
Issue
1
Pages
140-148.e3
ISSN
0890-8567 (ISSN-L)
DOI
10.1016/j.jaac.2019.02.013
PMC
PMC8056885
OpenAlex
W2920067933
Semantic Scholar
8e8750b46f39d38ab7382133cae9429a5aa060dd
Cited by
43
References
52
Citations by year
2026: 1 · 2025: 23 · 2024: 1 · 2023: 9 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 3
FWCI
2.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American Academy of Child & Adolescent Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute of Mental Health
  • NIMH
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • NICHD
  • National Science Foundation
  • NSF
  • National Institutes of Health
  • NIH
  • Russell Sage Foundation
  • Harris Foundation
  • Substance Abuse and Mental Health Services Administration
  • SAMHSA
  • Jacobs Foundation
  • Patient-Centered Outcomes Research Institute
  • Tulane University
Topics
  • Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
  • Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Keywords
telomere length, psychopathology, internalizing problems, externalizing problems, general psychopathology, childhood adversity, psychosocial deprivation, child abuse, telomere shortening, Bucharest Early Intervention Project, reciprocal effects
MeSH terms
Adolescent, Child, Female, Humans, Longitudinal Studies, Male, Psychopathology, Psychosocial Deprivation, Telomere, Telomere Shortening

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