Risk and resilience: genetic and environmental influences on development of the stress response

Gillespie, Charles F.; Phifer, Justine; Bradley, Bekh; Ressler, Kerry J.

doi:10.1002/da.20605

Cited by 352Stress Responses and CortisolChild Abuse and TraumaPosttraumatic Stress Disorder Research

Risk and resilience: genetic and environmental influences on development of the stress response

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Gillespie, Charles F., Phifer, Justine, Bradley, Bekh, Ressler, Kerry J.·2009·Depression and Anxiety

DOI 10.1002/da.20605PMC PMC2852579

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Abstract

Exposure to stressful events during development has consistently been shown to produce long-lasting alterations in the hypothalamic-pituitary-adrenal (HPA) axis, which may increase vulnerability to disease, including posttraumatic stress disorder and other mood and anxiety disorders. Recently reported genetic association studies indicate that these effects may be mediated, in part, by genexenvironment interactions involving polymorphisms within two key genes, CRHR1 and FKBP5. Data suggest that these genes regulate HPA axis function in conjunction with exposure to child maltreatment or abuse. In addition, a large and growing body of preclinical research suggests that increased activity of the amygdala-HPA axis induced by experimental manipulation of the amygdala mimics several of the physiological and behavioral symptoms of stress-related psychiatric illness in humans. Notably, interactions between the developing amygdala and HPA axis underlie critical periods for emotional learning, which are modulated by developmental support and maternal care. These translational findings lead to an integrated hypothesis: high levels of early life trauma lead to disease through the developmental interaction of genetic variants with neural circuits that regulate emotion, together mediating risk and resilience in adults.

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To date, findings mainly implicate two key genes: the GC response element (GRE) and the CRH-releasing hormone receptor 1 (CRHR1) of the FKBP5 gene.
“To date, findings mainly implicate two key genes: the GC response element (GRE) and the CRH-releasing hormone receptor 1 (CRHR1) of the FKBP5 gene (383, 384).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [383]
The section “Integration of Data on Variations of CRHR1 and FKBP5 and Childhood Abuse” (page unavailable) discusses CRHR1 and FKBP5 as distinct genes whose variation may affect risk after childhood abuse. It does not identify a glucocorticoid response element (GRE) as one of those genes or describe CRHR1 as part of FKBP5. (LLM, conf=0.88)
Experimental — accuracy not yet measured
ELS/CT during critical periods of brain development crucially affects the interaction between developing brain regions and neural circuits, exerts epigenetic influences and alters the functions of the HPA axis and GCs; it is associated with remarkable structural and functional brain changes even decades later in adulthood, defining both vulnerability and resilience.
“ELS/CT during critical periods of brain development crucially affects the interaction between developing brain regions and neural circuits, exerts epigenetic influences and alters the functions of the HPA axis and GCs; indeed, it has been associated with remarkable structural and functional brain changes even decades later, in adulthood, defining both vulnerability and resilience (383, 415, 416) [”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [383]
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Experimental — accuracy not yet measured
More recent findings suggest a vital role of genes involved with HPA axis function and GC sensitivity, in conjunction with exposure to child maltreatment or abuse.
“More recent findings suggest a vital role of genes involved with HPA axis function and GC sensitivity, in conjunction with exposure to child maltreatment or abuse (383).”
From Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation (2019) · cites this paper as [383]
Extensive evidence documents perturbed hypothalamic-pituitary-adrenal axis function as a result of early life stress and in depression and certain anxiety disorders, particularly PTSD.
“there is extensive evidence documenting perturbed HPA function both as a result of ELS and in the context of depression and certain anxiety disorders (particularly PTSD)”
From Gene–environment interactions: early life stress and risk for depressive and anxiety disorders (2011) · cites this paper as Gillespie et al. 2009

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Squirrel Monkey Immunophilin FKBP51 Is a Potent Inhibitor of Glucocorticoid Receptor Binding1
Denny, W. B., Valentine, D. L., Reynolds, P. D., Smith, D. F., & Scammell, J. G. (2000) · Endocrinology · doi:10.1210/en.141.11.4107 · Cited by 66 · see citing works
A population‐based association study of candidate genes for depression and sleep disturbance
Utge, S., Soronen, P., Partonen, T., Loukola, A., Kronholm, E., Pirkola, S. P., Nyman, E., Porkka‐Heiskanen, T., & Paunio, T. (2009) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.31002 · Cited by 62 · see citing works
Increased Number of Corticotropin-Releasing Hormone Expressing Neurons in the Hypothalamic Paraventricular Nucleus of Patients with Multiple Sclerosis
Purba, J. S., Raadsheer, F. C., Hofman, M. A., Ravid, R., Polman, C. H., Kamphorst, W., & Swaab, D. F. (2008) · Neuroendocrinology · doi:10.1159/000126989 · Cited by 58 · see citing works
Implication of brain corticosteroid receptor diversity for the adaptation syndrome concept.
de Kloet, E. R., Joëls, M., Oitzl, M. S., & Sutanto, W. (1991) · PubMed · Cited by 49 · see citing works
Postmortem and Cerebrospinal Fluid Studies of Corticotropin‐releasing Factor in Humansa
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Psychological stress in childhood and susceptibility to the chronic diseases of aging: Moving toward a model of behavioral and biological mechanisms.
Miller, G. E., Chen, E., & Parker, K. J. (2011) · Psychological Bulletin · doi:10.1037/a0024768 · Cited by 1,785 · see citing works
What is Resilience?
Herrman, H., Stewart, D. E., Diaz-Granados, N., Berger, E. L., Jackson, B., & Yuen, T. (2011) · The Canadian Journal of Psychiatry · doi:10.1177/070674371105600504 · Cited by 1,338 · see citing works
Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor
Ressler, K. J., Mercer, K. B., Bradley, B., Jovanovic, T., Mahan, A., Kerley, K., Norrholm, S. D., Kilaru, V., Smith, A. K., Myers, A. J., et al. (2011) · Nature · doi:10.1038/nature09856 · Cited by 800 · see citing works
Self-citation
Understanding resilience
Wu, G., Feder, A., Cohen, H., Kim, J. J., Calderon, S., Charney, D. S., & Mathé, A. A. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00010 · Cited by 780 · see citing works
Sex differences and stress across the lifespan
Bale, T. L., & Epperson, C. N. (2015) · Nature Neuroscience · doi:10.1038/nn.4112 · Cited by 751 · see citing works
Inflamed moods: A review of the interactions between inflammation and mood disorders
Rosenblat, J. D., Cha, D. S., Mansur, R. B., & McIntyre, R. S. (2014) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2014.01.013 · Cited by 609 · see citing works
Stress and the HPA axis: role of glucocorticoids in alcohol dependence
Stephens, M. (2012) · Alcohol Research: Current Reviews · doi:10.35946/arcr.v34.4.11 · Cited by 571 · see citing works
The origins of neuroticism
Barlow, D. H., Ellard, K. K., Sauer-Zavala, S., Bullis, J. R., & Carl, J. R. (2014) · Perspectives on Psychological Science · doi:10.1177/1745691614544528 · Cited by 491 · see citing works
Aging and Hearing Health: The Life-course Approach
Davis, A. C., McMahon, C. M., Pichora-Fuller, K. M., Russ, S. A., Lin, F. R., Olusanya, B. O., Chadha, S. K., & Tremblay, K. L. (2016) · The Gerontologist · doi:10.1093/geront/gnw033 · Cited by 410 · see citing works
Developmental Trajectories of Early Life Stress and Trauma: A Narrative Review on Neurobiological Aspects Beyond Stress System Dysregulation
Agorastos, A., Pervanidou, P., Chrousos, G. P., & Baker, D. G. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00118 · Cited by 385 · see citing works
“To date, findings mainly implicate two key genes: the GC response element (GRE) and the CRH-releasing hormone receptor 1 (CRHR1) of the FKBP5 gene (383, 384).”
Background
Severe Life Stress and Oxidative Stress in the Brain: From Animal Models to Human Pathology
Schiavone, S., Jaquet, V., Trabace, L., & Krause, K. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4720 · Cited by 350 · see citing works
Comorbidities and continuities as ontogenic processes: Toward a developmental spectrum model of externalizing psychopathology
Beauchaine, T. P., & McNulty, T. (2013) · Development and Psychopathology · doi:10.1017/s0954579413000746 · Cited by 288 · see citing works
Gene-environment interaction and psychiatric disorders: Review and future directions
Assary, E., Vincent, J. P., Keers, R., & Pluess, M. (2017) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2017.10.016 · Cited by 275 · see citing works
Variant Brain-Derived Neurotrophic Factor Val66Met Polymorphism Alters Vulnerability to Stress and Response to Antidepressants
Yu, H., Wang, D.-D., Wang, Y., Liu, T., Lee, F. S., & Chen, Z.-Y. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5048-11.2012 · Cited by 275 · see citing works
High anxiety trait: A vulnerable phenotype for stress‐induced depression
Weger, M., & Sandi, C. (2018) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.01.012 · Cited by 234 · see citing works
Gene–environment interactions: early life stress and risk for depressive and anxiety disorders
Nugent, N. R., Tyrka, A. R., Carpenter, L. L., & Price, L. H. (2011) · Psychopharmacology · doi:10.1007/s00213-010-2151-x · Cited by 269 · see citing works
“Since altered sensitivity of GRs is thought to mediate HPA axis dysregulation in depression and PTSD (Raison and Miller 2003), genes regulating components of this system are likely candidates for GxE investigations of the etiopathology of depression and anxiety (Charney 2004; Wust et al. 2004a; Wust et al. 2004b).”
BackgroundInfluential
Naturalistic rodent models of chronic early‐life stress
Molet, J., Maras, P. M., Avishai‐Eliner, S., & Baram, T. Z. (2014) · Developmental Psychobiology · doi:10.1002/dev.21230 · Cited by 258 · see citing works
Diseases, Disorders, and Comorbidities of Interoception
Bonaz, B., Lane, R. D., Oshinsky, M. L., Kenny, P. J., Sinha, R., Mayer, E. A., & Critchley, H. D. (2021) · Trends in Neurosciences · doi:10.1016/j.tins.2020.09.009 · Cited by 260 · see citing works
The involvement of FK506-binding protein 51 (FKBP5) in the behavioral and neuroendocrine effects of chronic social defeat stress
Hartmann, J., Wagner, K. V., Liebl, C., Scharf, S. H., Wang, X.-D., Wolf, M., Hausch, F., Rein, T., Schmidt, U., Touma, C., et al. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.07.041 · Cited by 224 · see citing works
Enhanced Cortisol Response to Stress in Children in Autism
Spratt, E. G., Nicholas, J. S., Brady, K. T., Carpenter, L. A., Hatcher, C. R., Meekins, K. A., Furlanetto, R. W., & Charles, J. M. (2012) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-011-1214-0 · Cited by 222 · see citing works
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
Chetty, S., Friedman, A., Taravosh-Lahn, K., Kirby, E. D., Mirescu, C., Guo, F., Krupik, D., Nicholas, A., Geraghty, A., Krishnamurthy, A., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.190 · Cited by 245 · see citing works
Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence
Essex, M. J., Shirtcliff, E. A., Burk, L. R., Ruttle, P. L., Klein, M. H., Slattery, M. J., Kalin, N. H., & Armstrong, J. M. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000484 · Cited by 212 · 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
Using Polymorphisms in FKBP5 to Define Biologically Distinct Subtypes of Posttraumatic Stress Disorder: Evidence From Endocrine and Gene Expression Studies
Mehta, D. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.50 · Cited by 200 · see citing works
Stress and trauma: BDNF control of dendritic-spine formation and regression
Bennett, M. R., & Lagopoulos, J. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.10.005 · Cited by 199 · see citing works
Adapting to Stress: Understanding the Neurobiology of Resilience
Osório, C., Probert, T., Jones, E., Young, A. H., & Robbins, I. (2016) · Behavioral Medicine · doi:10.1080/08964289.2016.1170661 · Cited by 186 · see citing works
Steroid up-regulation of FKBP51 and its role in hormone signaling
Jääskeläinen, T., Makkonen, H., & Palvimo, J. J. (2011) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2011.04.006 · Cited by 167 · see citing works
Periodic maternal separation decreases hippocampal neurogenesis without affecting basal corticosterone during the stress hyporesponsive period, but alters HPA axis and coping behavior in adulthood
Lajud, N., Roque, A., Cajero, M., Gutiérrez‐Ospina, G., & Torner, L. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.07.011 · Cited by 162 · see citing works
Adolescent social isolation increases anxiety-like behavior and ethanol intake and impairs fear extinction in adulthood: Possible role of disrupted noradrenergic signaling
Skelly, M. J., Chappell, A. E., Carter, E., & Weiner, J. L. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.05.025 · Cited by 161 · see citing works
Genetic Determinants of Depression: Recent Findings and Future Directions
Dunn, E. C., Brown, R. C., Dai, Y., Rosand, J., Nugent, N. R., Amstadter, A. B., & Smoller, J. W. (2015) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000054 · Cited by 158 · see citing works
Genetics of anxiety disorders: Genetic epidemiological and molecular studies in humans
Shimada‐Sugimoto, M., Otowa, T., & Hettema, J. M. (2015) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.12291 · Cited by 159 · see citing works
Developmental timing of trauma exposure and emotion dysregulation in adulthood: Are there sensitive periods when trauma is most harmful?
Dunn, E. C., Nishimi, K. M., Gomez, S. H., Powers, A. D., & Bradley, B. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.10.045 · Cited by 154 · see citing works
Self-citation
Early life stress and cortisol: A meta-analysis
Fogelman, N., & Canli, T. (2018) · Hormones and Behavior · doi:10.1016/j.yhbeh.2017.12.014 · Cited by 153 · see citing works
Cortisol, heart rate, and blood pressure as early markers of PTSD risk: A systematic review and meta-analysis
Morris, M. C., Hellman, N. M., Abelson, J. L., & Rao, U. (2016) · Clinical Psychology Review · doi:10.1016/j.cpr.2016.09.001 · Cited by 151 · see citing works
Hsp90 and FKBP51: complex regulators of psychiatric diseases
Criado‐Marrero, M., Rein, T., Binder, E. B., Porter, J. T., Koren, J., & Blair, L. J. (2017) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0532 · Cited by 145 · 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
Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks
Sarapas, C., Cai, G., Bierer, L. M., Golier, J. A., Galea, S., Ising, M., Rein, T., Schmeidler, J., Müller-Myhsok, B., Uhr, M., et al. (2011) · Disease Markers · doi:10.1155/2011/328054 · Cited by 143 · see citing works
The cumulative effect of different childhood trauma types on self-reported symptoms of adult male depression and PTSD, substance abuse and health-related quality of life in a large active-duty military cohort
Agorastos, A., Pittman, J. O. E., Angkaw, A. C., Nievergelt, C. M., Hansen, C. J., Aversa, L. H., Parisi, S. A., Barkauskas, D. A., & Baker, D. G. (2014) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2014.07.014 · Cited by 138 · see citing works
Schizotypy from a developmental perspective
Debbane, M., & Barrantes-Vidal, N. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu175 · Cited by 133 · see citing works
Different susceptibility to social defeat stress of BalbC and C57BL6/J mice
Razzoli, M., Carboni, L., Andreoli, M., Ballottari, A., & Arban, R. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.07.014 · Cited by 147 · see citing works
Hsp90 regulates tau pathology through co-chaperone complexes in Alzheimer's disease
Salminen, A., Ojala, J. O., Kaarniranta, K., Hiltunen, M., & Soininen, H. S. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.10.006 · Cited by 129 · see citing works
Altered metabotropic glutamate receptor 5 markers in PTSD: In vivo and postmortem evidence
Holmes, S. E., Girgenti, M. J., Davis, M. T., Pietrzak, R. H., DellaGioia, N., Nabulsi, N., Matuskey, D., Southwick, S. M., Duman, R. S., Carson, R. E., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701749114 · Cited by 129 · see citing works
Depression and Obesity: Integrating the Role of Stress, Neuroendocrine Dysfunction and Inflammatory Pathways
Ouakinin, S. R. S., Barreira, D. P., & Gois, C. J. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00431 · Cited by 125 · see citing works
Genetic approaches to understanding post-traumatic stress disorder
Almli, L. M., Fani, N., Smith, A. K., & Ressler, K. J. (2014) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145713001090 · Cited by 124 · see citing works
Self-citation
Early life stress and trauma: developmental neuroendocrine aspects of prolonged stress system dysregulation
Agorastos, A., Pervanidou, P., Chrousos, G. P., & Kolaitis, G. A. (2018) · HORMONES · doi:10.1007/s42000-018-0065-x · Cited by 124 · see citing works
Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5)
Tyrka, A. R., Ridout, K. K., Parade, S. H., Paquette, A., Marsit, C. J., & Seifer, R. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000991 · Cited by 118 · see citing works
The protective role of life satisfaction, coping strategies and defense mechanisms on perceived stress due to COVID-19 emergency: A chained mediation model
Gori, A., Topino, E., & Fabio, A. D. (2020) · PLoS ONE · doi:10.1371/journal.pone.0242402 · Cited by 116 · see citing works
A history of why fathers’ RNA matters†
Gòdia, M., Swanson, G., & Krawetz, S. A. (2018) · Biology of Reproduction · doi:10.1093/biolre/ioy007 · Cited by 113 · see citing works
Susceptibility to PTSD-Like Behavior Is Mediated by Corticotropin-Releasing Factor Receptor Type 2 Levels in the Bed Nucleus of the Stria Terminalis
Lebow, M., Neufeld-Cohen, A., Kuperman, Y., Tsoory, M., Gil, S., & Chen, A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.4012-11.2012 · Cited by 109 · see citing works
Mechanisms of neuroplasticity linking early adversity to depression: developmental considerations
Ho, T. C., & King, L. S. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01639-6 · Cited by 108 · see citing works
Posttraumatic stress disorder in anorexia nervosa
Reyes-Rodríguez, M. L., Von Holle, A., Ulman, T. F., Thornton, L. M., Klump, K. L., Brandt, H., Crawford, S., Fichter, M. M., Halmi, K. A., Huber, T., et al. (2011) · Psychosomatic Medicine · doi:10.1097/psy.0b013e31822232bb · Cited by 106 · see citing works
Endocannabinoid Signaling Collapse Mediates Stress-Induced Amygdalo-Cortical Strengthening
Marcus, D. J., Bedse, G., Gaulden, A. D., Ryan, J. D., Kondev, V., Winters, N. D., Rosas-Vidal, L. E., Altemus, M., Mackie, K., Lee, F. S., et al. (2020) · Neuron · doi:10.1016/j.neuron.2019.12.024 · Cited by 104 · see citing works
Childhood Trauma and Hippocampal and Amygdalar Volumes in First-Episode Psychosis
Hoy, K., Barrett, S., Shannon, C., Campbell, C., Watson, D., Rushe, T., Shevlin, M., Bai, F., Cooper, S., & Mulholland, C. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr085 · Cited by 103 · see citing works
Examining the Theory of Historical Trauma Among Native Americans
Brown-Rice, K. A. (2013) · The Professional Counselor · doi:10.15241/kbr.3.3.117 · Cited by 104 · see citing works
Glucocorticoids Modulate the mTOR Pathway in the Hippocampus: Differential Effects Depending on Stress History
Polman, J. A. E., Hunter, R. G., Speksnijder, N., van den Oever, J. M. E., Korobko, O. B., McEwen, B. S., de Kloet, E. R., & Datson, N. A. (2012) · Endocrinology · doi:10.1210/en.2012-1255 · Cited by 100 · see citing works
The prospect of FKBP51 as a drug target
Schmidt, M. V., Paez‐Pereda, M., Holsboer, F., & Hausch, F. (2012) · ChemMedChem · doi:10.1002/cmdc.201200137 · Cited by 99 · see citing works
Single-Nucleotide Polymorphism of the FKBP5 Gene and Childhood Maltreatment as Predictors of Structural Changes in Brain Areas Involved in Emotional Processing in Depression
Tozzi, L., Carballedo, A., Wetterling, F., McCarthy, H., O’Keane, V., Gill, M., Morris, D., Fahey, C., Meaney, J. F., & Frodl, T. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.170 · Cited by 97 · see citing works
Higher FKBP5, COMT, CHRNA5, and CRHR1 allele burdens are associated with PTSD and interact with trauma exposure: implications for neuropsychiatric research and treatment
Boscarino, J., Erlich, P., Hoffman, S., & Zhang, X.-P. (2012) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s29508 · Cited by 100 · see citing works
Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin
Meerveld, B. G., & Johnson, A. C. (2017) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2017.00086 · Cited by 97 · see citing works
Childhood maltreatment, juvenile disorders and adult post-traumatic stress disorder: a prospective investigation
Breslau, N., Koenen, K. C., Luo, Z., Agnew-Blais, J., Swanson, S., Houts, R. M., Poulton, R., & Moffitt, T. E. (2014) · Psychological Medicine · doi:10.1017/s0033291713002651 · Cited by 95 · see citing works
Sensitizing effect of early adversity on depressive reactions to later proximal stress: Moderation by 5-HTTLPR and CRHR1 in a 20-year longitudinal study
Starr, L., Hammen, C., Conway, C., Raposa, E. B., & Brennan, P. (2014) · Development and Psychopathology · doi:10.1017/s0954579414000996 · Cited by 67 · see citing works
Racial Disparities in Posttraumatic Stress After Diagnosis of Localized Breast Cancer: The BQUAL Study
Vin‐Raviv, N., Hillyer, G. C., Hershman, D. L., Galea, S., Leoce, N., Bovbjerg, D. H., Kushi, L. H., Kroenke, C. H., Lamerato, L. E., Ambrosone, C. B., et al. (2013) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djt024 · Cited by 90 · see citing works
Childhood trauma exposure in Iraq and Afghanistan war era veterans: Implications for posttraumatic stress disorder symptoms and adult functional social support
Voorhees, E. E. V., Dedert, E. A., Calhoun, P. S., Brancu, M., Runnals, J. J., & Beckham, J. C. (2012) · Child Abuse & Neglect · doi:10.1016/j.chiabu.2012.03.004 · Cited by 90 · see citing works
Association of FKBP5, COMT and CHRNA5 polymorphisms with PTSD among outpatients at risk for PTSD
Boscarino, J. A., Erlich, P. M., Hoffman, S. N., Rukstalis, M. R., & Stewart, W. F. (2011) · Psychiatry Research · doi:10.1016/j.psychres.2011.03.002 · Cited by 87 · see citing works
Depression as an evolutionary strategy for defense against infection
Anders, S. L., Tanaka, M., & Kinney, D. K. (2012) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2012.12.002 · Cited by 84 · see citing works
Childhood adversity and allostatic overload of the hypothalamic–pituitary–adrenal axis: A vulnerability model for depressive disorders
Wilkinson, P. O., & Goodyer, I. M. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000472 · Cited by 86 · see citing works
Affiliation buffers stress: cumulative genetic risk in oxytocin–vasopressin genes combines with early caregiving to predict PTSD in war-exposed young children
Feldman, R., Vengrober, A., & Ebstein, R. P. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.6 · Cited by 85 · see citing works
Corticotrophin-releasing hormone type 1 receptor gene (CRHR1) variants predict posttraumatic stress disorder onset and course in pediatric injury patients.
Amstadter, A. B., Nugent, N. R., Yang, B., Miller, A. B., Siburian, R., Moorjani, P., Haddad, S. A., Basu, A., Fagerness, J. A., Saxe, G., et al. (2011) · Europe PMC (PubMed Central) · doi:10.3233/dma-2011-0761 · Cited by 83 · see citing works
Corticosteroid Induced Decoupling of the Amygdala in Men
Henckens, M. J. A. G., van Wingen, G. A., Joëls, M., & Fernández, G. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr313 · Cited by 80 · see citing works
Amygdalar MicroRNA-15a Is Essential for Coping with Chronic Stress
Volk, N., Pape, J. C., Engel, M., Zannas, A. S., Cattane, N., Cattaneo, A., Binder, E. B., & Chen, A. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.038 · Cited by 79 · see citing works
Title: “Labels Matter: Is it stress or is it Trauma?”
Richter‐Levin, G., & Sandi, C. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01514-4 · Cited by 82 · see citing works
Systematic review, structural analysis, and new theoretical perspectives on the role of serotonin and associated genes in the etiology of psychopathy and sociopathy
Yildirim, B. O., & Derksen, J. J. L. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.04.009 · Cited by 75 · see citing works
Corticotrophin-Releasing Hormone Type 1 Receptor Gene (CRHR1) Variants Predict Posttraumatic Stress Disorder Onset and Course in Pediatric Injury Patients
Amstadter, A. B., Nugent, N. R., Yang, B., Miller, A. B., Siburian, R., Moorjani, P., Haddad, S. A., Basu, A., Fagerness, J. A., Saxe, G., et al. (2011) · Disease Markers · doi:10.1155/2011/928497 · Cited by 72 · see citing works
The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: moderation by FK506 binding protein 5 haplotype
Dackis, M. N., Rogosch, F. A., Oshri, A., & Cicchetti, D. (2012) · Development and Psychopathology · doi:10.1017/s0954579412000673 · Cited by 71 · see citing works
Molecular and cell signaling targets for PTSD pathophysiology and pharmacotherapy
Hauger, R. L., Olivares-Reyes, J. A., Dautzenberg, F. M., Lohr, J. B., Braun, S., & Oakley, R. H. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.11.007 · Cited by 71 · see citing works
Childhood Trauma Exposure and Toxic Stress: What the PNP Needs to Know
Hornor, G. (2015) · Journal of Pediatric Health Care · doi:10.1016/j.pedhc.2014.09.006 · Cited by 74 · see citing works
Women in recovery from PTSD have similar inflammation and quality of life as non-traumatized controls
Gill, J., Saligan, L. N., Lee, H., Rotolo, S., & Szanton, S. L. (2012) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2012.10.013 · Cited by 67 · see citing works
Blood-based gene-expression biomarkers of post-traumatic stress disorder among deployed marines: A pilot study
Tylee, D. S., Chandler, S. D., Nievergelt, C. M., Liu, X., Pazol, J., Woelk, C. H., Lohr, J. B., Kremen, W. S., Baker, D. G., Glatt, S. J., et al. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.024 · Cited by 65 · see citing works
Molecular genetics of hypothalamic–pituitary–adrenal axis activity and function
Mormède, P., Foury, A., Barat, P., Corcuff, J., Terenina, E. E., Marissal‐Arvy, N., & Moisan, M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05902.x · Cited by 65 · see citing works
Psychological resilience and neurocognitive performance in a traumatized community sample
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Authors: Gillespie, C. F., Phifer, J., Bradley, B., & Ressler, K. J.
Affiliations: Emory University (US)
Howard Hughes Medical Institute (US)
Corresponding author: Ressler, Kerry J.
ORCID: Gillespie, Charles F.
Bradley, Bekh
Ressler, Kerry J.
Venue: Depression and Anxiety
Publisher: Wiley
Published: 2009-11
Volume: 26
Issue: 11
Pages: 984-992
ISSN: 1091-4269 (ISSN-L)
1520-6394
DOI: 10.1002/da.20605
PMC: PMC2852579
OpenAlex: W2143123443
Cited by: 351
References: 82
Citations by year: 2026: 8 · 2025: 11 · 2024: 15 · 2023: 9 · 2022: 12 · 2021: 18 · 2020: 32 · 2019: 21 · 2018: 21 · 2017: 18 · 2016: 23 · 2015: 23 · 2014: 31 · 2013: 24 · 2012: 38
FWCI: 1.51
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: public-domain
doi.wiley.com/10.1002/tdm_license_1.1 (tdm, 2130 d)
Locations: Depression and Anxiety (publishedVersion, public-domain)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Howard Hughes Medical Institute
American Foundation for Suicide Prevention
National Alliance for Research on Schizophrenia and Depression
National Institutes of Health (UL1TR000454)
National Institute of Mental Health (K23MH082256, MH082256, MH 071537, R01MH071537, R56MH071537)
National Center for Advancing Translational Sciences
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
Keywords: stress response, hypothalamic-pituitary-adrenal axis, child abuse, early trauma, CRHR1, FKBP5, gene-environment interaction, amygdala, maternal care, emotional learning, post-traumatic stress disorder, anxiety disorders, resilience
MeSH terms: CRF Receptor, Type 1, Tacrolimus Binding Protein 5, Adult, Amygdala, Anxiety Disorders, Arousal, Child, Child Abuse, Emotions, Humans, Hypothalamo-Hypophyseal System, Life Change Events, Nerve Net, Pituitary-Adrenal System, Polymorphism, Genetic, Social Environment, Socioeconomic Factors, Stress Disorders, Post-Traumatic, Receptors, Corticotropin-Releasing Hormone, Mood Disorders, Genetic Predisposition to Disease, Tacrolimus Binding Proteins, Resilience, Psychological

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