Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults

Tyrka, Audrey R.; Ridout, Kathryn K.; Parade, Stephanie H.

doi:10.1017/s0954579416000870

Cited by 119Child Abuse and TraumaStress Responses and CortisolEpigenetics and DNA Methylation

Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults

Open access

Tyrka, Audrey R., Ridout, Kathryn K., Parade, Stephanie H.·2016·Development and Psychopathology

DOI 10.1017/s0954579416000870PMC PMC5330387

Open this paper in CoChat — free account

Abstract

Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus–pituitary–adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects. We present recent evidence related to epigenetic regulation of genes involved in hypothalamus–pituitary–adrenal axis regulation, namely, the glucocorticoid receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506 binding protein 51 gene (FKBP5), after childhood adversity and associations with risk for psychiatric disorders. Implications for the development of interventions and future research are discussed.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1017/s0954579416000870

Cites

173 of 173 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Studies across animals and humans point to altered methylation and expression of GR (NR3C1) and FKBP5 following ELS.
“Studies across animals and humans point to altered methylation and expression of the glucocorticoid receptor (GR or NR3C1) and FKBP5, a GR chaperone protein which impedes GR signaling, following ELS [79–81].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [79]
The ‘Childhood Adversity and Methylation of NR3C1’ section (page not available) links early adversity to NR3C1 methylation in humans and reports reduced gene expression in rodent models. The FKBP5 section (page not available) links childhood maltreatment to altered FKBP5 methylation, but its evidence of increased FKBP5 expression comes from glucocorticoid-treated cells, not a direct measurement following early-life stress. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Several studies have shown ELS is associated with GR hypermethylation in youth, though findings for FKBP5 are mixed.
“several studies have now shown that ELS is associated with GR hypermethylation in youth, though findings for FKBP5 have so far been mixed [79].”
From Trauma, PTSD, and the Developing Brain (2017) · cites this paper as [79]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Relationship of Childhood Abuse and Household Dysfunction to Many of the Leading Causes of Death in Adults
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A. M., Edwards, V., Koss, M. P., & Marks, J. S. (1998) · American Journal of Preventive Medicine · doi:10.1016/s0749-3797(98)00017-8 · Cited by 18,943 · see citing works
Child abuse: Adolescent records vs. adult recall
Femina, D. D., Yeager, C. A., & Lewis, D. O. (1990) · Child Abuse & Neglect · doi:10.1016/0145-2134(90)90033-p · Cited by 8,820 · see citing works
Effects of stress throughout the lifespan on the brain, behaviour and cognition
Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2639 · Cited by 6,256 · see citing works
Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177 · see citing works
Physiology and neurobiology of stress and adaptation: central role of the brain
McEwen, B. S. (2007) · Physiological Reviews · doi:10.1152/physrev.00041.2006 · Cited by 4,981 · cited 2× · see citing works
“Excessive stimulation by severe or prolonged stress may result in adaptive changes that alter function of the HPA axis (Doom, Cicchetti, & Rogosch, 2014; Fries, Hesse, Hellhammer, & Hellhammer, 2005; Heim, Ehlert, & Hellhammer, 2000; McEwen, 2007; Pryce et al., 2005; Tyrka et al., 2008).”
Background
DNA methylation and its basic function
Moore, L. D., Le, T., & Fan, G. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.112 · Cited by 4,906 · see citing works
Stress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621 · see citing works
CpG islands and the regulation of transcription
Deaton, A. M., & Bird, A. (2011) · Genes & Development · doi:10.1101/gad.2037511 · Cited by 3,187 · see citing works
Psychological Stress and Disease
Cohen, S., Janicki-Deverts, D., & Miller, G. E. (2007) · JAMA · doi:10.1001/jama.298.14.1685 · Cited by 3,168 · see citing works
If it goes up, must it come down? Chronic stress and the hypothalamic-pituitary-adrenocortical axis in humans.
Miller, G. E., Chen, E., & Zhou, E. S. (2007) · Psychological Bulletin · doi:10.1037/0033-2909.133.1.25 · Cited by 2,467 · see citing works
Childhood Adversities and Adult Psychiatric Disorders in the National Comorbidity Survey Replication I: Associations With First Onset of DSM-IV Disorders
Green, J. G., McLaughlin, K. A., Berglund, P. A., Gruber, M. J., Sampson, N. A., Zaslavsky, A. M., & Kessler, R. C. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2009.186 · Cited by 2,323 · see citing works
The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders
Heim, C., Ehlert, U., & Hellhammer, D. H. (2000) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(99)00035-9 · Cited by 1,688 · see citing works
Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex
McEwen, B. S., Nasca, C., & Gray, J. D. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2015.171 · Cited by 1,574 · see citing works
Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., Pace, T. W. W., Mercer, K. B., Mayberg, H. S., Bradley, B., et al. (2013) · Nature Neuroscience · doi:10.1038/nn.3275 · Cited by 1,447 · see citing works
Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008) · Epigenetics · doi:10.4161/epi.3.2.6034 · Cited by 1,432 · see citing works
Mechanisms of stress in the brain
McEwen, B. S., Bowles, N. P., Gray, J. D., Hill, M. N., Hunter, R. G., Karatsoreos, I. N., & Nasca, C. (2015) · Nature Neuroscience · doi:10.1038/nn.4086 · Cited by 1,386 · see citing works
Adverse childhood experiences and the risk of premature mortality
Brown, D. W., Anda, R. F., Tiemeier, H., Felitti, V. J., Edwards, V. J., Croft, J. B., & Giles, W. H. (2009) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2009.06.021 · Cited by 1,369 · see citing works
A new view on hypocortisolism
Fries, E., Hesse, J., Hellhammer, J., & Hellhammer, D. H. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.04.006 · Cited by 1,204 · see citing works
Covalent Modification of DNA Regulates Memory Formation
Miller, C. A., & Sweatt, J. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.022 · Cited by 1,180 · see citing works
Toward an Ecological/Transactional Model of Community Violence and Child Maltreatment: Consequences for Children’s Development
Cicchetti, D., & Lynch, M. (1993) · Psychiatry · doi:10.1080/00332747.1993.11024624 · Cited by 1,152 · see citing works
The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders
Binder, E. B. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.05.021 · Cited by 968 · see citing works
Low cortisol and a flattening of expected daytime rhythm: Potential indices of risk in human development
GUNNAR, M. R., & VAZQUEZ, D. M. (2001) · Development and Psychopathology · doi:10.1017/s0954579401003066 · Cited by 900 · see citing works
The Biological Effects of Childhood Trauma
De Bellis, M. D., & Zisk, A. (2014) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2014.01.002 · Cited by 892 · see citing works
Glucocorticoid receptor signaling in health and disease
Kadmiel, M., & Cidlowski, J. A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.07.003 · Cited by 849 · see citing works
Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation
Yehuda, R., Daskalakis, N. P., Bierer, L. M., Bader, H. N., Klengel, T., Holsboer, F., & Binder, E. B. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.08.005 · Cited by 782 · see citing works
Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood
Weaver, I. C. G., Meaney, M. J., & Szyf, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507526103 · Cited by 771 · see citing works
Untitled work
(2000) · PubMed · Cited by 676 · see citing works
A review of adversity, the amygdala and the hippocampus: a consideration of developmental timing
Tottenham, N. (2009) · Frontiers in Human Neuroscience · doi:10.3389/neuro.09.068.2009 · Cited by 651 · see citing works
DNA Methylation of the First Exon Is Tightly Linked to Transcriptional Silencing
Brenet, F. A., Moh, M., Funk, P., Feierstein, E., Viale, A. J., Socci, N. D., & Scandura, J. M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0014524 · Cited by 627 · see citing works
Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus
Levenson, J. M., Roth, T. L., Lubin, F. D., Miller, C. A., Huang, I.-C., Desai, P., Malone, L. M., & Sweatt, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511767200 · Cited by 615 · see citing works
Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells
Galon, J., Franchimont, D., Hiroi, N., Frey, G., Boettner, A., Ehrhart-Bornstein, M., O’shea, J. J., Chrousos, G. P., & Bornstein, S. R. (2002) · The FASEB Journal · doi:10.1096/fj.01-0245com · Cited by 606 · see citing works
Research Review: The neurobiology and genetics of maltreatment and adversity
McCrory, E., De Brito, S. A., & Viding, E. (2010) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02271.x · Cited by 598 · see citing works
The glucocorticoid receptor: Pivot of depression and of antidepressant treatment?
Anacker, C., Zunszain, P. A., Carvalho, L. A., & Pariante, C. M. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.03.007 · Cited by 592 · see citing works
Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment
Carpenter, L. L., Carvalho, J. P., Tyrka, A. R., Wier, L. M., Mello, A. F., Mello, M. F., Anderson, G. M., Wilkinson, C. W., & Price, L. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.002 · Cited by 564 · see citing works
Self-citation
Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression is involved in impaired DNA methylation and changes in histone modifications
Lillycrop, K. A., Slater-Jefferies, J. L., Hanson, M. A., Godfrey, K. M., Jackson, A. A., & Burdge, G. C. (2007) · British Journal Of Nutrition · doi:10.1017/s000711450769196x · Cited by 563 · see citing works
Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., Meyer, A., & Elbert, T. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.21 · Cited by 511 · cited 4× · see citing works
“…and tissues including umbilical cord blood (Hompes et al., 2013; Kertes et al., 2016; Mulligan et al., 2012; Oberlander et al., 2008), placenta (Conradt et al., 2013; Kertes et al., 2016), buccal cells in infancy (Braithwaite et al., 2015), and whole blood in adolescents (Radtke et al., 2011).”
BackgroundInfluential
Childhood Adversity and Epigenetic Modulation of the Leukocyte Glucocorticoid Receptor: Preliminary Findings in Healthy Adults
Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030148 · Cited by 486 · see citing works
Self-citation
Relations among posttraumatic stress disorder, comorbid major depression, and HPA function: A systematic review and meta-analysis
Morris, M. C., Compas, B. E., & Garber, J. (2012) · Clinical Psychology Review · doi:10.1016/j.cpr.2012.02.002 · Cited by 466 · cited 3× · see citing works
“A meta-analysis of 6,000 trauma-exposed participants with and without PTSD (Morris et al., 2012) showed that relative to nonexposed participants, those with PTSD as well as those with both PTSD and MDD had lower morning cortisol, lower daily output of cortisol, and lower cortisol response to…”
BackgroundMethodInfluential
Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression
Barden, N. (2004) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn.0421 · Cited by 416 · see citing works
Long-term effects of early-life environmental manipulations in rodents and primates: Potential animal models in depression research
Pryce, C. R., Rüedi‐Bettschen, D., Dettling, A. C., Weston, A. A., Russig, H. D., Ferger, B., & Feldon, J. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.011 · Cited by 414 · see citing works
Acute corticosterone treatment is sufficient to induce anxiety and amygdaloid dendritic hypertrophy
Mitra, R., & Sapolsky, R. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705615105 · Cited by 409 · see citing works
Hypocortisolism and increased glucocorticoid sensitivity of pro-Inflammatory cytokine production in Bosnian war refugees with posttraumatic stress disorder
Rohleder, N., Joksimovic, L., Wolf, J. M., & Kirschbaum, C. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.11.018 · Cited by 393 · see citing works
Effects of an attachment-based intervention on the cortisol production of infants and toddlers in foster care
Dozier, M., Peloso, E., Lewis, E., Laurenceau, J.-P., & Levine, S. (2008) · Development and Psychopathology · doi:10.1017/s0954579408000400 · Cited by 377 · see citing works
Diminished cortisol responses to psychosocial stress associated with lifetime adverse events
Elzinga, B. M., Roelofs, K., Tollenaar, M. S., Bakvis, P., van Pelt, J., & Spinhoven, P. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.11.004 · Cited by 364 · see citing works
Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD
Yehuda, R., Daskalakis, N. P., Desarnaud, F., Makotkine, I., Lehrner, A. L., Koch, E., Flory, J. D., Buxbaum, J. D., Meaney, M. J., & Bierer, L. M. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00118 · Cited by 358 · see citing works
Glucocorticoid receptor gene (NR3C1) methylation processes as mediators of early adversity in stress-related disorders causality: A critical review
Palma-Gudiel, H., Córdova-Palomera, A., Leza, J. C., & Fañanás, L. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.016 · Cited by 347 · see citing works
The Consequences of Early‐Life Adversity: Neurobiological, Behavioural and Epigenetic Adaptations
Maccari, S., Krugers, H. J., Morley‐Fletcher, S., Moshe Szyf, A., & Brunton, P. J. (2014) · Journal of Neuroendocrinology · doi:10.1111/jne.12175 · Cited by 347 · see citing works
Epigenetic Mechanisms for the Early Environmental Regulation of Hippocampal Glucocorticoid Receptor Gene Expression in Rodents and Humans
Zhang, T. Y., Labonté, B., Wen, X. L., Turecki, G., & Meaney, M. J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2012.149 · Cited by 347 · see citing works
Differential Glucocorticoid Receptor Exon 1B, 1C, and 1H Expression and Methylation in Suicide Completers with a History of Childhood Abuse
Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., & Turecki, G. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.034 · Cited by 345 · see citing works
Valproate Induces Replication-independent Active DNA Demethylation
Detich, N., Bovenzi, V., & Szyf, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303740200 · Cited by 345 · see citing works
Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight
Mulligan, C., D'Errico, N., Stees, J., & Hughes, D. (2012) · Epigenetics · doi:10.4161/epi.21180 · Cited by 342 · see citing works
Effects of a therapeutic intervention for foster preschoolers on diurnal cortisol activity
Fisher, P. A., Stoolmiller, M., Gunnar, M. R., & Burraston, B. O. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.06.008 · Cited by 337 · see citing works
Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry
Weder, N., Zhang, H., Jensen, K., Yang, B. Z., Simen, A., Jackowski, A., Lipschitz, D., Douglas-Palumberi, H., Ge, M., Perepletchikova, F., et al. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2013.12.025 · Cited by 324 · see citing works
The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells
Provençal, N., Suderman, M. J., Guillemin, C., Massart, R., Ruggiero, A., Wang, D., Bennett, A. J., Pierre, P. J., Friedman, D. P., Côté, S. M., et al. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.1470-12.2012 · Cited by 312 · see citing works
Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls
Ising, M., Depping, A., Siebertz, A., Lucae, S., Unschuld, P. G., Kloiber, S. M., Horstmann, S., Uhr, M., Müller‐Myhsok, B., & Holsboer, F. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06332.x · Cited by 312 · see citing works
Effect of childhood physical abuse on cortisol stress response
Carpenter, L. L., Shattuck, T. T., Tyrka, A. R., Geracioti, T. D., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2007-4 · Cited by 307 · see citing works
Self-citation
Neural regulation of the stress response: glucocorticoid feedback mechanisms
Herman, J. P., McKlveen, J. M., Solomon, M. B., Carvalho-Netto, E., & Myers, B. (2012) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2012007500041 · Cited by 307 · see citing works
Maternal prenatal depressive symptoms predict infantNR3C11F andBDNFIV DNA methylation
Braithwaite, E., Kundakovic, M., Ramchandani, P., Murphy, S., & Champagne, F. (2015) · Epigenetics · doi:10.1080/15592294.2015.1039221 · Cited by 299 · see citing works
The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior
Conradt, E. D., Lester, B. M., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013) · Epigenetics · doi:10.4161/epi.26634 · Cited by 299 · see citing works
Prolonged behavioral stress enhances synaptic connectivity in the basolateral amygdala
Vyas, A., Jadhav, S., & Chattarji, S. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.08.003 · Cited by 299 · see citing works
Associations Between Early Life Stress and Gene Methylation in Children
Romens, S. E., McDonald, J., Svaren, J., & Pollak, S. D. (2015) · Child Development · doi:10.1111/cdev.12270 · Cited by 299 · see citing works
Lower Methylation of Glucocorticoid Receptor Gene Promoter 1F in Peripheral Blood of Veterans with Posttraumatic Stress Disorder
Yehuda, R., Flory, J. D., Bierer, L. M., Henn-Haase, C., Lehrner, A., Desarnaud, F., Makotkine, I., Daskalakis, N. P., Marmar, C. R., & Meaney, M. J. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.02.006 · Cited by 293 · see citing works
High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: Interplay between clinical and animal studies
Zohar, J., Yahalom, H., Kozlovsky, N., Cwikel-Hamzany, S., Matar, M. A., Kaplan, Z., Yehuda, R., & Cohen, H. (2011) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2011.06.001 · Cited by 292 · see citing works
Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation
Dong, E., Nelson, M., Grayson, D. R., Costa, E., & Guidotti, A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805493105 · Cited by 284 · see citing works
Effect of childhood emotional abuse and age on cortisol responsivity in adulthood
Carpenter, L. L., Tyrka, A. R., Ross, N. S., Khoury, L., Anderson, G. M., & Price, L. H. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.02.030 · Cited by 281 · see citing works
Self-citation
Minireview: Stress-related psychiatric disorders with low cortisol levels: A metabolic hypothesis
Yehuda, R., & Seckl, J. (2011) · Endocrinology · doi:10.1210/en.2011-1218 · Cited by 276 · see citing works
Gene–environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism
Zannas, A. S., & Binder, E. B. (2013) · Genes Brain & Behavior · doi:10.1111/gbb.12104 · Cited by 268 · see citing works
Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood
Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., Schops, G., Dom, M., Van Bree, R., Freson, K., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.03.009 · Cited by 262 · see citing works
Chronic childhood adversity and onset of psychopathology during three life stages: Childhood, adolescence and adulthood
Benjet, C. L., Borges, G. L. G., & Medina‐Mora, M. E. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.01.004 · Cited by 261 · see citing works
Valproate Induces widespread epigenetic reprogramming which involves demethylation of specific genes
Milutinovic, S., D'Alessio, A. C., Detich, N., & Szyf, M. (2007) · Carcinogenesis · doi:10.1093/carcin/bgl167 · Cited by 256 · see citing works
Stress Leads to Contrasting Effects on the Levels of Brain Derived Neurotrophic Factor in the Hippocampus and Amygdala
Lakshminarasimhan, H., & Chattarji, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030481 · Cited by 253 · see citing works
Childhood parental loss and adult hypothalamic-pituitary-adrenal function
Tyrka, A. R., Wier, L., Price, L. H., Ross, N., Anderson, G. M., Wilkinson, C. W., & Carpenter, L. L. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.01.011 · Cited by 250 · see citing works
Self-citation
Childhood exposure to violence and lifelong health: Clinical intervention science and stress-biology research join forces
Moffitt, T. E., & Tank, T. K.-G. 2. T. (2013) · Development and Psychopathology · doi:10.1017/s0954579413000801 · Cited by 239 · see citing works
The Brain on Stress: Toward an Integrative Approach to Brain, Body, and Behavior
McEwen, B. S. (2013) · Perspectives on Psychological Science · doi:10.1177/1745691613506907 · Cited by 237 · see citing works
DNA methylation and childhood maltreatment: From animal models to human studies
Lutz, P.-E., & Turecki, G. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.07.069 · Cited by 236 · see citing works
Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic–Pituitary–Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo
Kertes, D. A., Kamin, H. S., Hughes, D. A., Rodney, N. C., Bhatt, S., & Mulligan, C. J. (2016) · Child Development · doi:10.1111/cdev.12487 · Cited by 219 · see citing works
Interventions to Improve Cortisol Regulation in Children: A Systematic Review
Slopen, N., McLaughlin, K. A., & Shonkoff, J. P. (2014) · Pediatrics · doi:10.1542/peds.2013-1632 · Cited by 211 · see citing works
Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression
Duman, R. S. (2009) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2009.11.3/rsduman · Cited by 210 · see citing works
Life course socioeconomic status and DNA methylation in genes related to stress reactivity and inflammation: The multi-ethnic study of atherosclerosis
Needham, B. L., Smith, J. A., Zhao, W., Wang, X., Mukherjee, B., Kardia, S. L. R., Shively, C. A., Seeman, T. E., Liu, Y., & Roux, A. V. D. (2015) · Epigenetics · doi:10.1080/15592294.2015.1085139 · Cited by 210 · see citing works
The Role of Life Events and HPA Axis in Anxiety Disorders: A Review
Faravelli, C., Lo Sauro, C., Lelli, L., Pietrini, F., Lazzeretti, L., Godini, L., Benni, L., Fioravanti, G., Alina Talamba, G., Castellini, G., et al. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803530907 · Cited by 208 · see citing works
Stress physiology and developmental psychopathology: Past, present, and future
Doom, J. R., & Gunnar, M. R. (2013) · Development and Psychopathology · doi:10.1017/s0954579413000667 · Cited by 204 · see citing works
Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD
Yehuda, R., Flory, J. D., Pratchett, L. C., Buxbaum, J. D., Ising, M., & Holsboer, F. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1969-6 · Cited by 202 · see citing works
In Search of HPA Axis Dysregulation in Child and Adolescent Depression
Guerry, J. D., & Hastings, P. D. (2011) · Clinical Child and Family Psychology Review · doi:10.1007/s10567-011-0084-5 · Cited by 195 · see citing works
Pre-Existing High Glucocorticoid Receptor Number Predicting Development of Posttraumatic Stress Symptoms After Military Deployment
van Zuiden, M., Geuze, E., Willemen, H. L. D. M., Vermetten, E., Maas, M., Heijnen, C. J., & Kavelaars, A. (2011) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10050706 · Cited by 190 · see citing works
Disentangling psychobiological mechanisms underlying internalizing and externalizing behaviors in youth: Longitudinal and concurrent associations with cortisol
Ruttle, P. L., Shirtcliff, E. A., Serbin, L. A., Fisher, D. B., Stack, D. M., & Schwartzman, A. E. (2010) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.10.015 · Cited by 188 · see citing works
Interactive Effects of Stress and Aging on Structural Plasticity in the Prefrontal Cortex
Bloss, E. B., Janssen, W. G. M., McEwen, B. S., & Morrison, J. H. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0759-10.2010 · Cited by 185 · see citing works
Intervention Effects on Diurnal Cortisol Rhythms of Child Protective Services–Referred Infants in Early Childhood
Bernard, K., Hostinar, C. E., & Dozier, M. (2014) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2014.2369 · Cited by 184 · see citing works
The Methyl Donor S-Adenosylmethionine Inhibits Active Demethylation of DNA
Detich, N., Hamm, S., Just, G., Knox, J. D., & Moshe Szyf, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211813200 · Cited by 179 · see citing works
Impact of early adversity on glucocorticoid regulation and later mental disorders
Strüber, N., Strüber, D., & Roth, G. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.10.015 · Cited by 173 · see citing works
The cortisol and glucocorticoid receptor response to low dose dexamethasone administration in aging combat veterans and holocaust survivors with and without posttraumatic stress disorder
Yehuda, R., Halligan, S. L., Grossman, R., Golier, J. A., & Wong, C. M. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01357-4 · Cited by 172 · see citing works
Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes
Kundaković, M., Lim, S. C., Gudsnuk, K. M., & Champagne, F. A. (2013) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2013.00078 · Cited by 172 · see citing works
Normalizing the development of cortisol regulation in maltreated infants through preventive interventions
Cicchetti, D., Rogosch, F. A., Toth, S. L., & Sturge-Apple, M. L. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000307 · Cited by 168 · see citing works
Epigenetic modification of the glucocorticoid receptor gene is linked to traumatic memory and post-traumatic stress disorder risk in genocide survivors
Vukojevic, V., Kolassa, I.-T., Fastenrath, M., Gschwind, L., Spalek, K., Milnik, A., Heck, A., Vogler, C., Wilker, S., Demougin, P., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1526-14.2014 · Cited by 168 · see citing works
Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study
van der Knaap, L. J., Riese, H., Hudziak, J. J., Verbiest, M. M. P. J., Verhulst, F. C., Oldehinkel, A. J., & van Oort, F. V. A. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.22 · Cited by 165 · see citing works
Interactions Between Maternal Parenting and Children’s Early Disruptive Behavior: Bidirectional Associations across the Transition from Preschool to School Entry
Combs-Ronto, L. A., Olson, S. L., Lunkenheimer, E. S., & Sameroff, A. J. (2009) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-009-9332-2 · Cited by 164 · see citing works
Timing matters: long term effects of adversities from prenatal period up to adolescence on adolescents' cortisol stress response. The TRAILS study
Bosch, N. M., Riese, H., Reijneveld, S. A., Bakker, M. P., Verhulst, F. C., Ormel, J., & Oldehinkel, A. J. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.01.013 · Cited by 163 · see citing works
Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder
Labonté, B., Azoulay, N., Yerko, V, Turecki, G., & Brunet, A. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.3 · Cited by 162 · see citing works
Epigenetic alterations in depression and antidepressant treatment
Menke, A., & Binder, E. B. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/amenke · Cited by 161 · see citing works
Melatonin in Medically Ill Patients With Insomnia
Andrade, C., Srihari, B. S., Reddy, K. P., & Chandramma, L. (2001) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v62n0109 · Cited by 158 · see citing works
Genetic variation in <scp>FKBP5</scp> associated with the extent of stress hormone dysregulation in major depression
Menke, A., Klengel, T., Rubel, J., Brückl, T., Pfister, H., Lucae, S., Uhr, M., Holsboer, F., & Binder, E. B. (2013) · Genes, Brain and Behavior · doi:10.1111/gbb.12026 · Cited by 151 · see citing works
DNA Modifications: Function and Applications in Normal and Disease States
Liyanage, V. R. B., Jarmasz, J. S., Murugeshan, N., Bigio, M. R. D., Rastegar, M., & Davie, J. (2014) · Biology · doi:10.3390/biology3040670 · Cited by 150 · see citing works
Integrating biological measures into the design and evaluation of preventive interventions
Cicchetti, D., & Gunnar, M. R. (2008) · Development and Psychopathology · doi:10.1017/s0954579408000357 · Cited by 148 · see citing works
Hypothalamic-Pituitary-Adrenal Axis Dysfunction and Illness Progression in Bipolar Disorder
Fries, G. R., Vasconcelos-Moreno, M. P., Gubert, C., Santos, B. T. M. Q. D., Sartori, J., Eisele, B. S., Ferrari, P., Fijtman, A., Rüegg, J., Gassen, N. C., et al. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu043 · Cited by 147 · see citing works
Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more
Turner, J. D., Alt, S. R., Cao, L., Vernocchi, S., Trifonova, S. T., Battello, N., & Muller, C. P. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.06.037 · Cited by 145 · see citing works
Association between Glucocorticoid Receptor Methylation and Hippocampal Subfields in Major Depressive Disorder
Na, K., Chang, H. S., Won, E., Han, K., Choi, S., Tae, W., Yoon, H., Kim, Y., Joe, S., Jung, I., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085425 · Cited by 144 · see citing works
The neurobiological correlates of childhood adversity and implications for treatment
Tyrka, A. R., Burgers, D. E., Philip, N. S., Price, L. H., & Carpenter, L. L. (2013) · Acta Psychiatrica Scandinavica · doi:10.1111/acps.12143 · Cited by 142 · see citing works
Self-citation
Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder
Martín-Blanco, A., Ferrer, M., Soler, J., Salazar, J., Vega, D., Andión, O., Sanchez-Mora, C., Arranz, M. J., Ribases, M., Feliu-Soler, A., et al. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.06.011 · Cited by 138 · see citing works
Increased DNA methylation of neuropsychiatric genes occurs in borderline personality disorder
Dammann, G., Teschler, S., Haag, T., Altmüller, F., Tuczek, F., & Dammann, R. (2011) · Epigenetics · doi:10.4161/epi.6.12.18363 · Cited by 137 · see citing works
Methylation of the glucocorticoid receptor gene promoter in bulimic women: Associations with borderline personality disorder, suicidality, and exposure to childhood abuse
Steiger, H., Labonté, B., Groleau, P., Turecki, G., & Israël, M. (2013) · International Journal of Eating Disorders · doi:10.1002/eat.22113 · Cited by 133 · see citing works
Glucocorticoid receptors in depression: relationship to the dexamethasone suppression test
Gormley, G. J., Lowy, M. T., Reder, A. T., Hospelhorn, V. D., Antel, J. P., & Meltzer, H. Y. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.11.1278 · Cited by 133 · see citing works
Placental FKBP5 Genetic and Epigenetic Variation Is Associated with Infant Neurobehavioral Outcomes in the RICHS Cohort
Paquette, A. G., Lester, B. M., Koestler, D. C., Lesseur, C., Armstrong, D. A., & Marsit, C. J. (2014) · PLoS ONE · doi:10.1371/journal.pone.0104913 · Cited by 131 · see citing works
Glucocorticoids Protect Against the Delayed Behavioral and Cellular Effects of Acute Stress on the Amygdala
Rao, R. P., Anilkumar, S., McEwen, B. S., & Chattarji, S. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.008 · Cited by 131 · see citing works
DNA methylation: Insights into human evolution
Hernando-Herraez, I., Garcia-Perez, R., Sharp, A. J., & Marques-Bonet, T. (2015) · PLOS Genetics · doi:10.1371/journal.pgen.1005661 · Cited by 128 · see citing works
Mitigating HPA axis dysregulation associated with placement changes in foster care
Fisher, P. A., Ryzin, M. J. V., & Gunnar, M. R. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.08.007 · Cited by 126 · see citing works
Modulation of glucocorticoid receptor nuclear translocation in neurons by immunophilins FKBP51 and FKBP52: Implications for major depressive disorder
Tatro, E. T., Everall, I. P., Kaul, M., & Achim, C. L. (2009) · Brain Research · doi:10.1016/j.brainres.2009.06.036 · Cited by 125 · see citing works
Cumulative Adversity in Childhood and Emergent Risk Factors for Long-Term Health
Slopen, N. B., Koenen, K. C., & Kubzansky, L. D. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.11.003 · Cited by 124 · see citing works
The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning
Conradt, E. D., Hawes, K., Guerin, D. J., Armstrong, D. A., Marsit, C. J., Tronick, E. Z., & Lester, B. M. (2016) · Child Development · doi:10.1111/cdev.12483 · Cited by 120 · see citing works
Valproate induces DNA demethylation in nuclear extracts from adult mouse brain
Dong, E., Chen, Y., Gavin, D. P., Grayson, D., & Guidotti, A. (2010) · Epigenetics · doi:10.4161/epi.5.8.13053 · Cited by 114 · see citing works
The impact of childhood maltreatment on biological systems: Implications for clinical interventions
González, A. (2013) · Paediatrics & Child Health · doi:10.1093/pch/18.8.415 · Cited by 110 · see citing works
Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links With Internalizing Behavior Problems
Parade, S. H., Ridout, K. K., Seifer, R., Armstrong, D. A., Marsit, C. J., McWilliams, M. A., & Tyrka, A. R. (2016) · Child Development · doi:10.1111/cdev.12484 · Cited by 109 · see citing works
Self-citation
Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: Systematic review of contributing factors
Daskalakis, N. P., & Yehuda, R. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00369 · Cited by 108 · see citing works
Hpa axis related genes and response to psychological therapies: Genetics and epigenetics
Roberts, S., Keers, R., Lester, K. J., Coleman, J. R. I., Breen, G., Arendt, K., Blatter‐Meunier, J., Cooper, P., Creswell, C., Fjermestad, K., et al. (2015) · Depression and Anxiety · doi:10.1002/da.22430 · Cited by 107 · see citing works
Maternal sensitivity, infant limbic structure volume and functional connectivity: a preliminary study
Rifkin-Graboi, A. E., Kong, L., Sim, L. W., Sanmugam, S., Broekman, B. F. P., Chen, H., Wong, E. Q., Kwek, K. Y. C., Saw, S., Chong, Y. S., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.133 · Cited by 106 · see citing works
Highly individual methylation patterns of alternative glucocorticoid receptor promoters suggest individualized epigenetic regulatory mechanisms
Turner, J. D., Pelascini, L. P. L., Macedo, J. A., & Muller, C. P. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn897 · Cited by 104 · see citing works
Effects of childhood trauma on HPA-axis reactivity in women free of lifetime psychopathology
Klaassens, E. R., van Noorden, M. S., Giltay, E. J., van Pelt, J., van Veen, T., & Zitman, F. G. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.04.011 · Cited by 101 · cited 1× · see citing works
“Several studies have replicated these findings (Carpenter, Shattuck, Tyrka, Geracioti, & Price, 2011; Carpenter et al., 2009; Elzinga et al., 2008; Klaassens, Giltay, van Veen, Veen, & Zitman, 2010; Klaassens et al., 2009; Tyrka et al., 2008).”
Result
FKBP5 polymorphism is associated with major depression but not with bipolar disorder
Szczepankiewicz, A., Leszczyńska-Rodziewicz, A., Pawlak, J., Narozna, B., Rajewska-Rager, A., Wilkosc, M., Zaremba, D., Maciukiewicz, M., & Twarowska-Hauser, J. (2014) · Journal of Affective Disorders · doi:10.1016/j.jad.2014.04.002 · Cited by 100 · see citing works
Longitudinal Patterns of Cortisol Regulation Differ in Maltreated and Nonmaltreated Children
Doom, J. R., Cicchetti, D., & Rogosch, F. A. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.08.006 · Cited by 98 · see citing works
Epigenetic regulation of theglucocorticoid receptorpromoter 17in adult rats
Witzmann, S. R., Turner, J. D., Mériaux, S. B., Meijer, O. C., & Muller, C. P. (2012) · Epigenetics · doi:10.4161/epi.22363 · Cited by 90 · see citing works
Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research
Armstrong, D. A., Lesseur, C., Conradt, E., Lester, B. M., & Marsit, C. J. (2014) · The FASEB Journal · doi:10.1096/fj.13-238402 · Cited by 89 · see citing works
Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: Relevance to depression
Skupio, U., Tertil, M., Sikora, M., Gołda, S., Wawrzczak‐Bargieła, A., & Przewłocki, R. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.11.035 · Cited by 88 · see citing works
Acute stress affects the global DNA methylation profile in rat brain: Modulation by physical exercise
Rodrigues, G. M., Toffoli, L. V., Manfredo, M. H. F., de Oliveira, J. F., Silva, A. S., Raquel, H. D. A., Martins‐Pinge, M. C., Moreira, E. G., Fernandes, K. B. P., Pelosi, G. G., et al. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.11.023 · Cited by 84 · see citing works
Folate, Vitamin B12, and S-Adenosylmethionine
Bottiglieri, T. (2013) · Psychiatric Clinics of North America · doi:10.1016/j.psc.2012.12.001 · Cited by 83 · see citing works
Environmental Stressors and Epigenetic Control of the Hypothalamic-Pituitary-Adrenal Axis
Lee, R. S., & Sawa, A. (2014) · Neuroendocrinology · doi:10.1159/000369585 · Cited by 78 · see citing works
Epigenetics, a key for unlocking complex CNS disorders? Therapeutic implications
Szyf, M. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2014.01.009 · Cited by 76 · see citing works
FKBP5 genotype-dependent DNA methylation and mRNA regulation after psychosocial stress in remitted depression and healthy controls
Hohne, N., Poidinger, M., Merz, F., Pfister, H., Bruckl, T., Zimmermann, P., Uhr, M., Holsboer, F., & Ising, M. (2015) · International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyu087 · Cited by 74 · see citing works
Within- and between-litter maternal care alter behavior and gene regulation in female offspring.
Pan, P., Fleming, A. S., Lawson, D. O., Jenkins, J. M., & McGowan, P. O. (2014) · Behavioral Neuroscience · doi:10.1037/bne0000014 · Cited by 72 · see citing works
Comparison of in vivo and in vitro glucocorticoid sensitivity in depression: Relationship to the dexamethasone suppression test
Lowy, M. T., Reder, A. T., Gormley, G. J., & Meltzer, H. Y. (1988) · Biological Psychiatry · doi:10.1016/0006-3223(88)90136-9 · Cited by 70 · see citing works
Effects of early adversity on young children's diurnal cortisol rhythms and externalizing behavior
Bernard, K., Zwerling, J., & Dozier, M. (2015) · Developmental Psychobiology · doi:10.1002/dev.21324 · Cited by 67 · see citing works
Long-Term Corticosterone Exposure Decreases Insulin Sensitivity and Induces Depressive-Like Behaviour in the C57BL/6NCrl Mouse
van Donkelaar, E. L., Vaessen, K. R. D., Pawluski, J. L., Sierksma, A. S. R., Blokland, A., Cañete, R., & Steinbusch, H. W. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106960 · Cited by 66 · see citing works
Behavioral adjustment in a community sample of boys: Links with basal and stress-induced salivary cortisol concentrations
Tyrka, A. R., Kelly, M. M., Graber, J. A., DeRose, L. M., Lee, J. K., Warren, M. P., & Jeanne Brooks-gunn, B. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.02.002 · Cited by 66 · see citing works
Self-citation
A transactional analysis of the relation between maternal sensitivity and child vagal regulation.
Perry, N. B., Mackler, J. S., Calkins, S. D., & Keane, S. P. (2013) · Developmental Psychology · doi:10.1037/a0033819 · Cited by 66 · see citing works
Patterns of brain activation in foster children and nonmaltreated children during an inhibitory control task
Bruce, J., Fisher, P. A., Graham, A. M., Moore, W. E., Peake, S. J., & Mannering, A. M. (2013) · Development and Psychopathology · doi:10.1017/s095457941300028x · Cited by 65 · see citing works
Organization and function of the FKBP52 and FKBP51 genes
Cioffi, D. L., Hubler, T. R., & Scammell, J. G. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.03.013 · Cited by 64 · see citing works
Placental Epigenetic Patterning of Glucocorticoid Response Genes is Associated with Infant Neurodevelopment
Paquette, A. G., Lester, B. M., Lesseur, C., Armstrong, D. A., Guerin, D. J., Appleton, A. A., & Marsit, C. J. (2015) · Epigenomics · doi:10.2217/epi.15.28 · Cited by 61 · see citing works
Methylation of exons 1D, 1F, and 1Hof the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children
Tyrka, A. R., Parade, S. H., Eslinger, N. M., Marsit, C. J., Lesseur, C., Armstrong, D. A., Philip, N. S., Josefson, B., & Seifer, R. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000176 · Cited by 60 · see citing works
Self-citation
FKBP5 moderation of depressive symptoms in peer victimized, post-institutionalized children
VanZomeren‐Dohm, A., Pitula, C. E., Koss, K. J., Thomas, K. M., & Gunnar, M. R. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.10.003 · Cited by 56 · see citing works
Sex and litter effects on anxiety and DNA methylation levels of stress and neurotrophin genes in adolescent rats
Kosten, T. A., Huang, W., & Nielsen, D. A. (2013) · Developmental Psychobiology · doi:10.1002/dev.21106 · Cited by 53 · see citing works
Dissection of glucocorticoid receptor-mediated inhibition of the hypothalamic–pituitary–adrenal axis by gene targeting in mice
Laryea, G. N., Muglia, L. M., Arnett, M. G., & Muglia, L. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.09.002 · Cited by 53 · see citing works
Hypothalamic-pituitary-adrenal axis dysfunction as a neurobiological correlate of emotion dysregulation in adolescent suicide
Braquehais, M. D., Picouto, M. D., Casas, M., & Sher, L. (2012) · World Journal of Pediatrics · doi:10.1007/s12519-012-0358-0 · Cited by 51 · see citing works
Physical exercise affects the epigenetic programming of rat brain and modulates the adaptive response evoked by repeated restraint stress
Kashimoto, R. K., Toffoli, L. V., Manfredo, M. H. F., Volpini, V. L., Martins‐Pinge, M. C., Pelosi, G. G., & Gomes, M. V. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.08.038 · Cited by 50 · see citing works
Telomeres, Early-Life Stress and Mental Illness
Ridout, S. J., Ridout, K. K., Kao, H., Carpenter, L. L., Philip, N. S., Tyrka, A. R., & Price, L. H. (2015) · Advances in psychosomatic medicine · doi:10.1159/000369088 · Cited by 47 · see citing works
Self-citation
Individual Differences in Childhood Behavior Disorders Associated With Epigenetic Modulation of the Cortisol Receptor Gene
Dadds, M. R., Moul, C., Hawes, D. J., Diaz, A. M., & Brennan, J. (2015) · Child Development · doi:10.1111/cdev.12391 · Cited by 47 · see citing works
Hydrocortisone responsiveness in Gulf War veterans with PTSD: Effects on ACTH, declarative memory hippocampal [18F]FDG uptake on PET
Yehuda, R., Golier, J. A., Bierer, L. M., Mikhno, A., Pratchett, L. C., Burton, C. L., Makotkine, I., Devanand, D. P., Pradhaban, G., Harvey, P. D., et al. (2010) · Psychiatry Research Neuroimaging · doi:10.1016/j.pscychresns.2010.06.010 · Cited by 44 · see citing works
The Genome- and System-Wide Response of DNA Methylation to Early Life Adversity and its Implication on Mental Health
Moshe Szyf, A. (2013) · The Canadian Journal of Psychiatry · doi:10.1177/070674371305801208 · Cited by 43 · see citing works
Methylation of NR3C1 and SLC6A4 and internalizing problems. The TRAILS study
van der Knaap, L. J., van Oort, F. V. A., Verhulst, F. C., Oldehinkel, A. J., & Riese, H. (2015) · Journal of Affective Disorders · doi:10.1016/j.jad.2015.03.056 · Cited by 40 · see citing works
The effects of stress during early postnatal periods on behavior and hippocampal neuroplasticity markers in adult male mice
van der Kooij, M. A., Grosse, J., Zanoletti, O., Papilloud, A., & Sandi, C. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.10.058 · Cited by 39 · see citing works
HPA stability for children in foster care: Mental health implications and moderation by early intervention
Laurent, H. K., Gilliam, K. S., Bruce, J., & Fisher, P. A. (2014) · Developmental Psychobiology · doi:10.1002/dev.21226 · Cited by 38 · see citing works
Role of the 5′-untranslated regions in post-transcriptional regulation of the human glucocorticoid receptor
Turner, J. D., Vernocchi, S., Schmitz, S., & Muller, C. P. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.08.010 · Cited by 38 · see citing works
Intervention Effects on Morning and Stimulated Cortisol Responses among Toddlers in Foster Care
Nelson, E. M. M., & Spieker, S. J. (2013) · Infant Mental Health Journal · doi:10.1002/imhj.21382 · Cited by 35 · see citing works
Trauma exposure in relation to basal salivary cortisol and the hormone response to the dexamethasone/CRH test in male railway employees without lifetime psychopathology.
Klaassens, E., Giltay, E., van Veen, T., Veen, G., & Zitman, F. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.11.012 · Cited by 33 · see citing works
A role for synapsin in FKBP51 modulation of stress responsiveness: Convergent evidence from animal and human studies
Schmidt, U., Buell, D. R., Ionescu, I. A., Gassen, N. C., Holsboer, F., Cox, M. B., Novak, B., Huber, C. W., Hartmann, J., Schmidt, M. V., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.11.005 · Cited by 32 · see citing works
Litter and sex effects on maternal behavior and DNA methylation of the Nr3c1 exon 17 promoter gene in hippocampus and cerebellum
Kosten, T. A., & Nielsen, D. A. (2014) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2014.03.010 · Cited by 30 · see citing works
Relationship between dexamethasone-inhibited lysozyme activity in peripheral mononuclear leukocytes and the cortisol and glucocorticoid receptor response to dexamethasone
Yehuda, R., Yang, R.-K., Guo, S. L., Makotkine, I., & Singh, B. (2003) · Journal of Psychiatric Research · doi:10.1016/s0022-3956(03)00073-6 · Cited by 29 · see citing works
Salivary cortisol: a possible biomarker in evaluating stress and effects of interventions in young foster children?
van Andel, H. W. H., Jansen, L. M. C., Grietens, H. W. E., Knorth, E. J., & van der Gaag, R. J. (2013) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-013-0439-1 · Cited by 29 · see citing works
Alterations of Glucocorticoid Receptor Gene Methylation in Externalizing Disorders During Childhood and Adolescence
Heinrich, A., Buchmann, A. F., Zohsel, K., Dukal, H., Frank, J., Treutlein, J., Nieratschker, V., Witt, S. H., Brandeis, D., Schmidt, M. H., et al. (2015) · Behavior Genetics · doi:10.1007/s10519-015-9721-y · Cited by 28 · see citing works
Rapid Activation of Glucocorticoid Receptors in the Prefrontal Cortex Mediates the Expression of Contextual Conditioned Fear in Rats
Reis, F. M., Almada, R. C., Fogaça, M. V., & Brandão, M. L. (2015) · Cerebral Cortex · doi:10.1093/cercor/bhv103 · Cited by 26 · see citing works
Neuroendocrine predictors of emotional and behavioral adjustment in boys: Longitudinal follow-up of a community sample
Tyrka, A. R., Lee, J. K., Graber, J. A., Clement, A. M., Kelly, M. M., DeRose, L. M., Warren, M. P., & Jeanne Brooks-gunn, B. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.04.004 · Cited by 21 · see citing works
Self-citation
Preserving neuroplasticity: Role of glucocorticoids and neurotrophins via phosphorylation
McEwen, B. S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1521416112 · Cited by 21 · see citing works
Possible association between haplotypes of the FKBP5 gene and suicidal bipolar disorder, but not with melancholic depression and psychotic features, in the course of bipolar disorder
Leszczyńska-Rodziewicz, A., Szczepankiewicz, A., Skibińska, M., Pawlak, J., Dmitrzak‐Węglarz, M., Hauser, J., & Narożna, B. (2014) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s54538 · Cited by 19 · see citing works
Corticosterone modulates fear responses and the expression of glucocorticoid receptors in the brain of high-anxiety rats
Wisłowska-Stanek, A., Lehner, M., Skórzewska, A., Maciejak, P., Szyndler, J., Turzyńska, D., Sobolewska, A., & Płaźnik, A. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.11.012 · Cited by 19 · see citing works
The Cellular Sequelae of Early Stress: Focus on Aging and Mitochondria
Ridout, K. K., Carpenter, L. L., & Tyrka, A. R. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.301 · Cited by 17 · see citing works
Self-citation
Effect of Topiramate on Glucocorticoid Receptor Mediated Action
Yehuda, R., Yang, R.-K., Golier, J. A., Tischler, L., Liong, B., & Decker, K. B. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300331 · Cited by 13 · see citing works
Relationship of the FKBP5 C/T polymorphism with dysfunctional attitudes predisposing to depression.
Suzuki, A., Matsumoto, Y., Sadahiro, R., Enokido, M., Goto, K., & Otani, K. (2014) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2014.04.019 · Cited by 10 · see citing works

Flagged first, then by citations

Sorted by citations

Sensitive periods for the effect of childhood adversity on DNA methylation: results from a prospective, longitudinal study
Dunn, E. C., Soare, T. W., Zhu, Y., Simpkin, A. J., Suderman, M. J., Klengel, T., Smith, A. D. A. C., Ressler, K. J., & Relton, C. L. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.12.023 · Cited by 315 · see citing works
Trauma, PTSD, and the Developing Brain
Herringa, R. J. (2017) · Current Psychiatry Reports · doi:10.1007/s11920-017-0825-3 · Cited by 248 · see citing works
Epigenetic changes of fkbp5 as a link connecting genetic and environmental risk factors with structural and functional brain changes in major depression
Tozzi, L., Farrell, C., Booij, L., Doolin, K., Nemoda, Z., Szyf, M., Pomares, F. B., Chiarella, J., O'Keane, V., & Frodl, T. (2018) · Neuropsychopharmacology · doi:10.1038/npp.2017.290 · Cited by 146 · see citing works
Intergenerational Effects of Maternal Holocaust Exposure on FKBP5 Methylation
Bierer, L. M., Bader, H. N., Daskalakis, N. P., Lehrner, A., Provençal, N., Wiechmann, T., Klengel, T., Makotkine, I., Binder, E. B., & Yehuda, R. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2019.19060618 · Cited by 86 · see citing works
Biological alterations affecting risk of adult psychopathology following childhood trauma: a review of sex differences
Tiwari, A., & Gonzalez, A. (2018) · Clinical Psychology Review · doi:10.1016/j.cpr.2018.01.006 · Cited by 71 · see citing works
Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment
Parent, J., Parade, S. H., Laumann, L. E., Ridout, K. K., Yang, B.-Z., Marsit, C. J., Seifer, R., & Tyrka, A. R. (2017) · Development and Psychopathology · doi:10.1017/s0954579417001298 · Cited by 72 · see citing works
Self-citation
Abnormal DNA methylation within HPA-axis genes years after paediatric critical illness
Coppens, G., Vanhorebeek, I., Güiza, F., Derese, I., Wouters, P. J., Téblick, A., Dulfer, K., Joosten, K. F., Verbruggen, S. C., & Van den Berghe, G. (2024) · Clinical Epigenetics · doi:10.1186/s13148-024-01640-y · Cited by 15 · see citing works

Effect of psychosocial stress on FKBP5 and NR3C1 gene expression in healthy young men
Höhne, N., Pfister, H., Brückl, T. M., et al. (2012) · European Journal of Psychotraumatology · doi:10.3402/ejpt.v3i0.19557 · Cited by 1 · see citing works
Mineralocorticoid receptors dampen glucocorticoid receptor sensitivity to stress via regulation of FKBP5
Hartmann, J., Bajaj, T., Klengel, C., Chatzinakos, C., Ebert, T., Dedic, N., McCullough, K. M., Lardenoije, R., Joëls, M., Meijer, O. C., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.109185 · Cited by 119 · see citing works
Giucocorticoid-Insensitive Bronchial Asthma
Lee, T. H., & Leung, D. Y. M. (2008) · Blackwell Science Ltd eBooks · doi:10.1002/9780470694923.ch33
[Medicinal activation and inhibition of function of glucocorticoid receptors as the basis for regulation of the glucocorticoid effect].
Pp, G. (1994) · PubMed · Cited by 1 · see citing works
A measure of glucocorticoid load provided by DNA methylation of Fkbp5 in mice
Lee, R. S., Tamashiro, K. L., Yang, X., Purcell, R. H., Huo, Y., Rongione, M. A., Potash, J. B., & Wand, G. S. (2011) · Psychopharmacology · doi:10.1007/s00213-011-2307-3 · Cited by 109 · see citing works

Authors: Tyrka, A. R., Ridout, K. K., & Parade, S. H.
Affiliations: Brown University (US)
Corresponding author: Tyrka, Audrey R.
ORCID: Tyrka, Audrey R.
Ridout, Kathryn K.
Parade, Stephanie H.
Venue: Development and Psychopathology
Publisher: Cambridge University Press (CUP)
Published: 2016-10-03
Volume: 28
Issue: 4pt2
Pages: 1319-1331
ISSN: 0954-5794 (ISSN-L)
1469-2198
DOI: 10.1017/s0954579416000870
PMC: PMC5330387
OpenAlex: W2528455892
Cited by: 119
References: 173
Citations by year: 2026: 1 · 2025: 12 · 2024: 9 · 2023: 10 · 2022: 5 · 2021: 32 · 2020: 14 · 2019: 11 · 2018: 20 · 2017: 5
FWCI: 1.78
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.cambridge.org/core/terms (unspecified)
Locations: Development and Psychopathology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute of Mental Health (R25MH101076, R01MH083704, K23MH067947, R01MH101107)
Topics: Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords: childhood adversity, child abuse, epigenetic regulation, DNA methylation, glucocorticoid signaling, hypothalamic-pituitary-adrenal axis, glucocorticoid receptor, NR3C1, FKBP5, mental illness, stress response, early life exposure
MeSH terms: Tacrolimus Binding Protein 5, Adult, Mental Disorders, Child, Child Abuse, Female, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Receptors, Glucocorticoid, Risk Factors, Social Environment, Stress, Psychological, Signal Transduction, Tacrolimus Binding Proteins, Epigenesis, Genetic

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.

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 ›

Are you an author, or do you see a problem with this page? Request a review

Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks