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Early life trauma, depression and the glucocorticoid receptor gene – an epigenetic perspective

  • C. Smart (a1), G. Strathdee (a2), S. Watson (a1) (a3), C. Murgatroyd (a4) and R. H. McAllister-Williams (a1) (a3)...

Abstract

Background.

Hopes to identify genetic susceptibility loci accounting for the heritability seen in unipolar depression have not been fully realized. Family history remains the ‘gold standard’ for both risk stratification and prognosis in complex phenotypes such as depression. Meanwhile, the physiological mechanisms underlying life-event triggers for depression remain opaque. Epigenetics, comprising heritable changes in gene expression other than alterations of the nucleotide sequence, may offer a way to deepen our understanding of the aetiology and pathophysiology of unipolar depression and optimize treatments. A heuristic target for exploring the relevance of epigenetic changes in unipolar depression is the hypothalamic–pituitary–adrenal (HPA) axis. The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life.

Method.

In this paper we discuss the progress that has been made by studies that have investigated the relationship between depression, early trauma, the HPA axis and the NR3C1 gene. Difficulties with the design of these studies are also explored.

Results.

Future efforts will need to comprehensively address epigenetic natural histories at the population, tissue, cell and gene levels. The complex interactions between the epigenome, genome and environment, as well as ongoing nosological difficulties, also pose significant challenges.

Conclusions.

The work that has been done so far is nevertheless encouraging and suggests potential mechanistic and biomarker roles for differential DNA methylation patterns in NR3C1 as well as novel therapeutic targets.

Copyright

Corresponding author

* Address for correspondence: C. Smart, Institute of Neuroscience, Newcastle University, Academic Psychiatry, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne NE4 5LP, UK. (Email: Chris.Smart@newcastle.ac.uk)

References

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Aberg, KA, McClay, JL, Nerella, S, Clark, S, Kumar, G, Chen, W, Khachane, AN, Xie, L, Hudson, A, Gao, G, Harada, A, Hultman, CM, Sullivan, PF, Magnusson, PK, van den Oord, EJ (2014). Methylome-wide association study of schizophrenia: identifying blood biomarker signatures of environmental insults. JAMA Psychiatry 71, 255264.
Akbarian, S, Huang, HS (2009). Epigenetic regulation in human brain – focus on histone lysine methylation. Biological Psychiatry 65, 198203.
Alt, SR, Turner, JD, Klok, MD, Meijer, OC, Lakke, EA, Derijk, RH, Muller, CP (2010). Differential expression of glucocorticoid receptor transcripts in major depressive disorder is not epigenetically programmed. Psychoneuroendocrinology 35, 544556.
Anacker, C, Zunszain, PA, Carvalho, LA, Pariante, CM (2011). The glucocorticoid receptor: pivot of depression and of antidepressant treatment? Psychoneuroendocrinology 36, 415425.
Anisman, H, Zaharia, MD, Meaney, MJ, Merali, Z (1998). Do early-life events permanently alter behavioral and hormonal responses to stressors? International Journal of Developmental Neuroscience 16, 149164.
Antypa, N, Serretti, A, Rujescu, D (2013). Serotonergic genes and suicide: a systematic review. European Neuropsychopharmacology 23, 11251142.
Archer, T, Oscar-Berman, M, Blum, K, Gold, M (2013). Epigenetic modulation of mood disorders. Journal of Genetic Syndromes and Gene Therapy 4, 1000120.
Aubry, JM, Gervasoni, N, Osiek, C, Perret, G, Rossier, MF, Bertschy, G, Bondolfi, G (2007). The DEX/CRH neuroendocrine test and the prediction of depressive relapse in remitted depressed outpatients. Journal of Psychiatric Research 41, 290294.
Babenko, O, Kovalchuk, I, Metz, GA (2015). Stress-induced perinatal and transgenerational epigenetic programming of brain development and mental health. Neuroscience and Biobehavioral Reviews 48C, 7091.
Bagot, RC, Labonte, B, Pena, CJ, Nestler, EJ (2014). Epigenetic signaling in psychiatric disorders: stress and depression. Dialogues in Clinical Neuroscience 16, 281295.
Bakulski, KM, Fallin, MD (2014). Epigenetic epidemiology: promises for public health research. Environmental and Molecular Mutagenesis 55, 171183.
Bale, TL, Baram, TZ, Brown, AS, Goldstein, JM, Insel, TR, McCarthy, MM, Nemeroff, CB, Reyes, TM, Simerly, RB, Susser, ES, Nestler, EJ (2010). Early life programming and neurodevelopmental disorders. Biological Psychiatry 68, 314319.
Barbosa, LP, Quevedo, L, da Silva Gdel, G, Jansen, K, Pinheiro, RT, Branco, J, Lara, D, Oses, J, da Silva, RA (2014). Childhood trauma and suicide risk in a sample of young individuals aged 14–35 years in southern Brazil. Child Abuse and Neglect 38, 11911196.
Belvederi Murri, M, Pariante, C, Mondelli, V, Masotti, M, Atti, AR, Mellacqua, Z, Antonioli, M, Ghio, L, Menchetti, M, Zanetidou, S, Innamorati, M, Amore, M (2014). HPA axis and aging in depression: systematic review and meta-analysis. Psychoneuroendocrinology 41, 4662.
Bifulco, A, Brown, GW, Adler, Z (1991). Early sexual abuse and clinical depression in adult life. British Journal of Psychiatry 159, 115122.
Binder, EB (2009). The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 34 (Suppl. 1), S186S195.
Binder, EB, Bradley, RG, Liu, W, Epstein, MP, Deveau, TC, Mercer, KB, Tang, Y, Gillespie, CF, Heim, CM, Nemeroff, CB, Schwartz, AC, Cubells, JF, Ressler, KJ (2008). Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299, 12911305.
Binder, EB, Salyakina, D, Lichtner, P, Wochnik, GM, Ising, M, Putz, B, Papiol, S, Seaman, S, Lucae, S, Kohli, MA, Nickel, T, Kunzel, HE, Fuchs, B, Majer, M, Pfennig, A, Kern, N, Brunner, J, Modell, S, Baghai, T, Deiml, T, Zill, P, Bondy, B, Rupprecht, R, Messer, T, Kohnlein, O, Dabitz, H, Bruckl, T, Muller, N, Pfister, H, Lieb, R, Mueller, JC, Lohmussaar, E, Strom, TM, Bettecken, T, Meitinger, T, Uhr, M, Rein, T, Holsboer, F, Muller-Myhsok, B (2004). Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nature Genetics 36, 13191325.
Bird, A (2002). DNA methylation patterns and epigenetic memory. Genes and Development 16, 621.
Bird, A (2007). Perceptions of epigenetics. Nature 447, 396398.
Bockmuhl, Y, Murgatroyd, CA, Kuczynska, A, Adcock, IM, Almeida, OF, Spengler, D (2011). Differential regulation and function of 5′-untranslated GR-exon 1 transcripts. Molecular Endocrinology 25, 11001110.
Bohacek, J, Gapp, K, Saab, BJ, Mansuy, IM (2013). Transgenerational epigenetic effects on brain functions. Biological Psychiatry 73, 313320.
Bohacek, J, Mansuy, IM (2013). Epigenetic inheritance of disease and disease risk. Neuropsychopharmacology 38, 220236.
Booij, L, Wang, D, Levesque, ML, Tremblay, RE, Szyf, M (2013). Looking beyond the DNA sequence: the relevance of DNA methylation processes for the stress–diathesis model of depression. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences 368, 20120251.
Bouma, EM, Riese, H, Nolte, IM, Oosterom, E, Verhulst, FC, Ormel, J, Oldehinkel, AJ (2011). No associations between single nucleotide polymorphisms in corticoid receptor genes and heart rate and cortisol responses to a standardized social stress test in adolescents: the TRAILS study. Behavior Genetics 41, 253261.
Bowes, L, Jaffee, SR (2013). Biology, genes, and resilience: toward a multidisciplinary approach. Trauma, Violence and Abuse 14, 195208.
Boyle, MP, Brewer, JA, Funatsu, M, Wozniak, DF, Tsien, JZ, Izumi, Y, Muglia, LJ (2005). Acquired deficit of forebrain glucocorticoid receptor produces depression-like changes in adrenal axis regulation and behavior. Proceedings of the National Academy of Sciences of the USA 102, 473478.
Brown, GW, Craig, TK, Harris, TO, Herbert, J, Hodgson, K, Tansey, KE, Uher, R (2014). Functional polymorphism in the brain-derived neurotrophic factor gene interacts with stressful life events but not childhood maltreatment in the etiology of depression. Depression and Anxiety 31, 326334.
Caldji, C, Diorio, J, Meaney, MJ (2000). Variations in maternal care in infancy regulate the development of stress reactivity. Biological Psychiatry 48, 11641174.
Calfa, G, Kademian, S, Ceschin, D, Vega, G, Rabinovich, GA, Volosin, M (2003). Characterization and functional significance of glucocorticoid receptors in patients with major depression: modulation by antidepressant treatment. Psychoneuroendocrinology 28, 687701.
Callaway, E (2014). Epigenomics starts to make its mark. Nature 508, 22.
Carpenter, LL, Carvalho, JP, Tyrka, AR, Wier, LM, Mello, AF, Mello, MF, Anderson, GM, Wilkinson, CW, Price, LH (2007). Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biological Psychiatry 62, 10801087.
Casey, BJ, Craddock, N, Cuthbert, BN, Hyman, SE, Lee, FS, Ressler, KJ (2013). DSM-5 and RDoC: progress in psychiatry research? Nature Reviews, Neuroscience 14, 810814.
Caspi, A, Sugden, K, Moffitt, TE, Taylor, A, Craig, IW, Harrington, H, McClay, J, Mill, J, Martin, J, Braithwaite, A, Poulton, R (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386389.
Castillo-Fernandez, JE, Spector, TD, Bell, JT (2014). Epigenetics of discordant monozygotic twins: implications for disease. Genome Medicine 6, 60.
Chang, SC, Glymour, MM, Walter, S, Liang, L, Koenen, KC, Tchetgen, EJ, Cornelis, MC, Kawachi, I, Rimm, E, Kubzansky, LD (2014). Genome-wide polygenic scoring for a 14-year long-term average depression phenotype. Brain and Behavior 4, 298311.
Cohen-Woods, S, Craig, IW, McGuffin, P (2013). The current state of play on the molecular genetics of depression. Psychological Medicine 43, 673687.
Collins, PY, Patel, V, Joestl, SS, March, D, Insel, TR, Daar, AS, Scientific Advisory Board and the Executive Committee of the Grand Challenges on Global Mental Health, Anderson, W, Dhansay, MA, Phillips, A, Shurin, S, Walport, M, Ewart, W, Savill, SJ, Bordin, IA, Costello, EJ, Durkin, M, Fairburn, C, Glass, RI, Hall, W, Huang, Y, Hyman, SE, Jamison, K, Kaaya, S, Kapur, S, Kleinman, A, Ogunniyi, A, Otero-Ojeda, A, Poo, MM, Ravindranath, V, Sahakian, BJ, Saxena, S, Singer, PA, Stein, DJ (2011). Grand challenges in global mental health. Nature 475, 2730.
Conradt, E, Lester, BM, Appleton, AA, Armstrong, DA, Marsit, CJ (2013). The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neurobehavior. Epigenetics 8, 13211329.
Cowen, PJ (2010). Not fade away: the HPA axis and depression. Psychological Medicine 40, 14.
Crean, AJ, Kopps, AM, Bonduriansky, R (2014). Revisiting telegony: offspring inherit an acquired characteristic of their mother's previous mate. Ecology Letters 17, 15451552.
Danchin, E, Charmantier, A, Champagne, FA, Mesoudi, A, Pujol, B, Blanchet, S (2011). Beyond DNA: integrating inclusive inheritance into an extended theory of evolution. Nature Reviews, Genetics 12, 475486.
Daniels, WM, Fairbairn, LR, van Tilburg, G, McEvoy, CR, Zigmond, MJ, Russell, VA, Stein, DJ (2009). Maternal separation alters nerve growth factor and corticosterone levels but not the DNA methylation status of the exon 1(7) glucocorticoid receptor promoter region. Metabolic Brain Disease 24, 615627.
Daskalakis, NP, Bagot, RC, Parker, KJ, Vinkers, CH, de Kloet, ER (2013). The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome. Psychoneuroendocrinology 38, 18581873.
Daskalakis, NP, Yehuda, R (2014). Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: systematic review of contributing factors. Frontiers in Neuroscience 8, 369.
Day, JJ, Sweatt, JD (2011). Epigenetic mechanisms in cognition. Neuron 70, 813829.
Dempster, EL, Pidsley, R, Schalkwyk, LC, Owens, S, Georgiades, A, Kane, F, Kalidindi, S, Picchioni, M, Kravariti, E, Toulopoulou, T, Murray, RM, Mill, J (2011). Disease-associated epigenetic changes in monozygotic twins discordant for schizophrenia and bipolar disorder. Human Molecular Genetics 20, 47864796.
Dempster, EL, Wong, CC, Lester, KJ, Burrage, J, Gregory, AM, Mill, J, Eley, TC (2014). Genome-wide methylomic analysis of monozygotic twins discordant for adolescent depression. Biological Psychiatry 76, 977983.
Denenberg, VH, Rosenberg, KM (1967). Nongenetic transmission of information. Nature 216, 549550.
Dyer, O (2014). Journal retracts article that said childhood trauma could lead to genetic changes. BMJ 349, g5543.
Eaves, L, Silberg, J, Erkanli, A (2003). Resolving multiple epigenetic pathways to adolescent depression. Journal of Child Psychology and Psychiatry, and Allied Disciplines 44, 10061014.
Edelman, S, Shalev, I, Uzefovsky, F, Israel, S, Knafo, A, Kremer, I, Mankuta, D, Kaitz, M, Ebstein, RP (2012). Epigenetic and genetic factors predict women's salivary cortisol following a threat to the social self. PLOS ONE 7, e48597.
Ehlert, U (2013). Enduring psychobiological effects of childhood adversity. Psychoneuroendocrinology 38, 18501857.
El-Sayed, AM, Haloossim, MR, Galea, S, Koenen, KC (2012). Epigenetic modifications associated with suicide and common mood and anxiety disorders: a systematic review of the literature. Biology of Mood and Anxiety Disorders 2, 10.
Elzinga, BM, Roelofs, K, Tollenaar, MS, Bakvis, P, van Pelt, J, Spinhoven, P (2008). Diminished cortisol responses to psychosocial stress associated with lifetime adverse events a study among healthy young subjects. Psychoneuroendocrinology 33, 227237.
Engineer, N, Darwin, L, Nishigandh, D, Ngianga-Bakwin, K, Smith, SC, Grammatopoulos, DK (2013). Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum. Journal of Psychiatric Research 47, 11661173.
Fineberg, NA, Haddad, PM, Carpenter, L, Gannon, B, Sharpe, R, Young, AH, Joyce, E, Rowe, J, Wellsted, D, Nutt, DJ, Sahakian, BJ (2013). The size, burden and cost of disorders of the brain in the UK. Journal of Psychopharmacology 27, 761770.
Finkelhor, D, Shattuck, A, Turner, HA, Hamby, SL (2014). The lifetime prevalence of child sexual abuse and sexual assault assessed in late adolescence. Journal of Adolescent Health 55, 329333.
Fish, EW, Shahrokh, D, Bagot, R, Caldji, C, Bredy, T, Szyf, M, Meaney, MJ (2004). Epigenetic programming of stress responses through variations in maternal care. Annals of the New York Academy of Sciences 1036, 167180.
Flint, J, Kendler, KS (2014). The genetics of major depression. Neuron 81, 484503.
Francis, D, Diorio, J, Liu, D, Meaney, MJ (1999). Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286, 11551158.
Francke, U, Foellmer, BE (1989). The glucocorticoid receptor gene is in 5q31-q32 [corrected]. Genomics 4, 610612.
Franz, CE, Lyons, MJ, O'Brien, R, Panizzon, MS, Kim, K, Bhat, R, Grant, MD, Toomey, R, Eisen, S, Xian, H, Kremen, WS (2011). A 35-year longitudinal assessment of cognition and midlife depression symptoms: the Vietnam Era Twin Study of Aging. American Journal of Geriatric Psychiatry 19, 559570.
Galecka, E, Szemraj, J, Bienkiewicz, M, Majsterek, I, Przybylowska-Sygut, K, Galecki, P, Lewinski, A (2013). Single nucleotide polymorphisms of NR3C1 gene and recurrent depressive disorder in population of Poland. Molecular Biology Reports 40, 16931699.
Gallagher, P, Watson, S, Smith, MS, Young, AH, Ferrier, IN (2007). Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder. Schizophrenia Research 90, 258265.
Gibbons, JL (1964). Cortisol secretion rate in depressive illness. Archives of General Psychiatry 10, 572575.
Glossop, JR, Nixon, NB, Emes, RD, Haworth, KE, Packham, JC, Dawes, PT, Fryer, AA, Mattey, DL, Farrell, WE (2013). Epigenome-wide profiling identifies significant differences in DNA methylation between matched-pairs of T- and B-lymphocytes from healthy individuals. Epigenetics 8, 11881197.
Gusev, A, Bhatia, G, Zaitlen, N, Vilhjalmsson, BJ, Diogo, D, Stahl, EA, Gregersen, PK, Worthington, J, Klareskog, L, Raychaudhuri, S, Plenge, RM, Pasaniuc, B, Price, AL (2013). Quantifying missing heritability at known GWAS loci. PLoS Genetics 9, e1003993.
Heerboth, S, Lapinska, K, Snyder, N, Leary, M, Rollinson, S, Sarkar, S (2014). Use of epigenetic drugs in disease: an overview. Genetics and Epigenetics 6, 919.
Heim, C, Nemeroff, CB (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biological Psychiatry 49, 10231039.
Heim, C, Newport, DJ, Mletzko, T, Miller, AH, Nemeroff, CB (2008). The link between childhood trauma and depression: insights from HPA axis studies in humans. Psychoneuroendocrinology 33, 693710.
Heim, C, Shugart, M, Craighead, WE, Nemeroff, CB (2010). Neurobiological and psychiatric consequences of child abuse and neglect. Developmental Psychobiology 52, 671690.
Hepgul, N, Cattaneo, A, Zunszain, PA, Pariante, CM (2013). Depression pathogenesis and treatment: what can we learn from blood mRNA expression? BMC Medicine 11, 28.
Herbert, J (2013). Cortisol and depression: three questions for psychiatry. Psychological Medicine 43, 449469.
Holliday, R, Pugh, JE (1975). DNA modification mechanisms and gene activity during development. Science 187, 226232.
Holsboer, F (2000). The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23, 477501.
Hompes, T, Izzi, B, Gellens, E, Morreels, M, Fieuws, S, Pexsters, A, Schops, G, Dom, M, Van Bree, R, Freson, K, Verhaeghe, J, Spitz, B, Demyttenaere, K, Glover, V, Van den Bergh, B, Allegaert, K, Claes, S (2013). 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. Journal of Psychiatric Research 47, 880891.
Hornung, OP, Heim, CM (2014). Gene–environment interactions and intermediate phenotypes: early trauma and depression. Frontiers in Endocrinology (Lausanne) 5, 14.
Hotchkiss, RD (1948). The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. Journal of Biological Chemistry 175, 315332.
Insel, T, Cuthbert, B, Garvey, M, Heinssen, R, Pine, DS, Quinn, K, Sanislow, C, Wang, P (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. American Journal of Psychiatry 167, 748751.
Ishida, K, Klevens, J, Rivera-Garcia, B, Mirabal, B (2013). Child maltreatment in Puerto Rico: findings from the 2010 National Child Abuse and Neglect Data System. Puerto Rico Health Sciences Journal 32, 124131.
Ising, M, Horstmann, S, Kloiber, S, Lucae, S, Binder, EB, Kern, N, Kunzel, HE, Pfennig, A, Uhr, M, Holsboer, F (2007). Combined dexamethasone/corticotropin releasing hormone test predicts treatment response in major depression – a potential biomarker? Biological Psychiatry 62, 4754.
Kanherkar, RR, Bhatia-Dey, N, Csoka, AB (2014). Epigenetics across the human lifespan. Frontiers in Cell and Developmental Biology 2, 49.
Karanth, S, Linthorst, AC, Stalla, GK, Barden, N, Holsboer, F, Reul, JM (1997). Hypothalamic–pituitary–adrenocortical axis changes in a transgenic mouse with impaired glucocorticoid receptor function. Endocrinology 138, 34763485.
Kendler, KS, Bulik, CM, Silberg, J, Hettema, JM, Myers, J, Prescott, CA (2000). Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis. Archives of General Psychiatry 57, 953959.
Kendler, KS, Gatz, M, Gardner, CO, Pedersen, NL (2006). A Swedish national twin study of lifetime major depression. American Journal of Psychiatry 163, 109114.
Kessing, LV, Willer, IS, Knorr, U (2011). Volume of the adrenal and pituitary glands in depression. Psychoneuroendocrinology 36, 1927.
Klengel, T, Pape, J, Binder, EB, Mehta, D (2014). The role of DNA methylation in stress-related psychiatric disorders. Neuropharmacology 80, 115132.
Koper, JW, van Rossum, EF, van den Akker, EL (2014). Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease. Steroids 92, 6273.
Labonte, B, Yerko, V, Gross, J, Mechawar, N, Meaney, MJ, Szyf, M, Turecki, G (2012). Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry 72, 4148.
Lahti, J, Raikkonen, K, Bruce, S, Heinonen, K, Pesonen, AK, Rautanen, A, Wahlbeck, K, Kere, J, Kajantie, E, Eriksson, JG (2011). Glucocorticoid receptor gene haplotype predicts increased risk of hospital admission for depressive disorders in the Helsinki birth cohort study. Journal of Psychiatric Research 45, 11601164.
Levinson, DF, Mostafavi, S, Milaneschi, Y, Rivera, M, Ripke, S, Wray, NR, Sullivan, PF (2014). Genetic studies of major depressive disorder: why are there no genome-wide association study findings and what can we do about it? Biological Psychiatry 76, 510512.
Lewis, CM, Ng, MY, Butler, AW, Cohen-Woods, S, Uher, R, Pirlo, K, Weale, ME, Schosser, A, Paredes, UM, Rivera, M, Craddock, N, Owen, MJ, Jones, L, Jones, I, Korszun, A, Aitchison, KJ, Shi, J, Quinn, JP, Mackenzie, A, Vollenweider, P, Waeber, G, Heath, S, Lathrop, M, Muglia, P, Barnes, MR, Whittaker, JC, Tozzi, F, Holsboer, F, Preisig, M, Farmer, AE, Breen, G, Craig, IW, McGuffin, P (2010). Genome-wide association study of major recurrent depression in the U.K. population. American Journal of Psychiatry 167, 949957.
Lewis, G, Collishaw, S, Harold, G, Rice, F, Thapar, A (2012). Maternal depression and child and adolescent depression symptoms: an exploratory test for moderation by CRHR1, FKBP5 and NR3C1 gene variants. Behavior Genetics 42, 121132.
Liu, D, Diorio, J, Tannenbaum, B, Caldji, C, Francis, D, Freedman, A, Sharma, S, Pearson, D, Plotsky, PM, Meaney, MJ (1997). Maternal care, hippocampal glucocorticoid receptors, and hypothalamic–pituitary–adrenal responses to stress. Science 277, 16591662.
Maher, B (2008). Personal genomes: the case of the missing heritability. Nature 456, 1821.
Maniglio, R (2009). The impact of child sexual abuse on health: a systematic review of reviews. Clinical Psychology Review 29, 647657.
Massart, R, Mongeau, R, Lanfumey, L (2012). Beyond the monoaminergic hypothesis: neuroplasticity and epigenetic changes in a transgenic mouse model of depression. Philosophical Transactions of the Royal Society of London, Series B, Biological Sciences 367, 24852494.
Mathers, JC, Strathdee, G, Relton, CL (2010). Induction of epigenetic alterations by dietary and other environmental factors. Advances in Genetics 71, 339.
May-Chahal, C, Cawson, P (2005). Measuring child maltreatment in the United Kingdom: a study of the prevalence of child abuse and neglect. Child Abuse and Neglect 29, 969984.
McAllister-Williams, RH, Ferrier, IN, Young, AH (1998). Mood and neuropsychological function in depression: the role of corticosteroids and serotonin. Psychological Medicine 28, 573584.
McGowan, PO, Sasaki, A, D'Alessio, AC, Dymov, S, Labonte, B, Szyf, M, Turecki, G, Meaney, MJ (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience 12, 342348.
McGuffin, P, Cohen, S, Knight, J (2007). Homing in on depression genes. American Journal of Psychiatry 164, 195197.
Meaney, MJ (2001). Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annual Review of Neuroscience 24, 11611192.
Meaney, MJ, Diorio, J, Francis, D, Widdowson, J, LaPlante, P, Caldji, C, Sharma, S, Seckl, JR, Plotsky, PM (1996). Early environmental regulation of forebrain glucocorticoid receptor gene expression: implications for adrenocortical responses to stress. Developmental Neuroscience 18, 4972.
Meaney, MJ, Szyf, M (2005). Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome. Dialogues in Clinical Neuroscience 7, 103123.
Medina, A, Seasholtz, AF, Sharma, V, Burke, S, Bunney, W Jr, Myers, RM, Schatzberg, A, Akil, H, Watson, SJ (2013). Glucocorticoid and mineralocorticoid receptor expression in the human hippocampus in major depressive disorder. Journal of Psychiatric Research 47, 307314.
Melas, PA, Wei, Y, Wong, CC, Sjoholm, LK, Aberg, E, Mill, J, Schalling, M, Forsell, Y, Lavebratt, C (2013). Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. International Journal of Neuropsychopharmacology 16, 15131528.
Moser, D, Molitor, A, Kumsta, R, Tatschner, T, Riederer, P, Meyer, J (2007). The glucocorticoid receptor gene exon 1-F promoter is not methylated at the NGFI-A binding site in human hippocampus. World Journal of Biological Psychiatry 8, 262268.
Mulligan, CJ, D'Errico, NC, Stees, J, Hughes, DA (2012). Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics 7, 853857.
Murgatroyd, C, Patchev, AV, Wu, Y, Micale, V, Bockmuhl, Y, Fischer, D, Holsboer, F, Wotjak, CT, Almeida, OF, Spengler, D (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience 12, 15591566.
Murgatroyd, C, Quinn, JP, Sharp, HM, Pickles, A, Hill, J (2015). Effects of prenatal and postnatal depression, and maternal stroking, at the glucocorticoid receptor gene. Translational Psychiatry 5, e560.
Murgatroyd, C, Spengler, D (2011). Epigenetics of early child development. Frontiers in Psychiatry 2, 16.
Murgatroyd, CA, Nephew, BC (2013). Effects of early life social stress on maternal behavior and neuroendocrinology. Psychoneuroendocrinology 38, 219228.
Murgatroyd, CA, Taliefar, M, Bradburn, S, Carini, LM, Babb, JA, Nephew, BC (2015). Social stress during lactation, depressed maternal care, and neuropeptidergic gene expression. Behavioural Pharmacology. Published online 8 June 2015. doi:10.1097/FBP.0000000000000147.
Murray, CJ, Vos, T, Lozano, R, Naghavi, M, Flaxman, AD, Michaud, C, Ezzati, M, Shibuya, K, Salomon, JA, Abdalla, S, Aboyans, V, Abraham, J, Ackerman, I, Aggarwal, R, Ahn, SY, Ali, MK, Alvarado, M, Anderson, HR, Anderson, LM, Andrews, KG, Atkinson, C, Baddour, LM, Bahalim, AN, Barker-Collo, S, Barrero, LH, Bartels, DH, Basanez, MG, Baxter, A, Bell, ML, Benjamin, EJ, Bennett, D, Bernabe, E, Bhalla, K, Bhandari, B, Bikbov, B, Bin Abdulhak, A, Birbeck, G, Black, JA, Blencowe, H, Blore, JD, Blyth, F, Bolliger, I, Bonaventure, A, Boufous, S, Bourne, R, Boussinesq, M, Braithwaite, T, Brayne, C, Bridgett, L, Brooker, S, Brooks, P, Brugha, TS, Bryan-Hancock, C, Bucello, C, Buchbinder, R, Buckle, G, Budke, CM, Burch, M, Burney, P, Burstein, R, Calabria, B, Campbell, B, Canter, CE, Carabin, H, Carapetis, J, Carmona, L, Cella, C, Charlson, F, Chen, H, Cheng, AT, Chou, D, Chugh, SS, Coffeng, LE, Colan, SD, Colquhoun, S, Colson, KE, Condon, J, Connor, MD, Cooper, LT, Corriere, M, Cortinovis, M, de Vaccaro, KC, Couser, W, Cowie, BC, Criqui, MH, Cross, M, Dabhadkar, KC, Dahiya, M, Dahodwala, N, Damsere-Derry, J, Danaei, G, Davis, A, De Leo, D, Degenhardt, L, Dellavalle, R, Delossantos, A, Denenberg, J, Derrett, S, Des Jarlais, DC, Dharmaratne, SD, Dherani, M, Diaz-Torne, C, Dolk, H, Dorsey, ER, Driscoll, T, Duber, H, Ebel, B, Edmond, K, Elbaz, A, Ali, SE, Erskine, H, Erwin, PJ, Espindola, P, Ewoigbokhan, SE, Farzadfar, F, Feigin, V, Felson, DT, Ferrari, A, Ferri, CP, Fevre, EM, Finucane, MM, Flaxman, S, Flood, L, Foreman, K, Forouzanfar, MH, Fowkes, FG, Fransen, M, Freeman, MK, Gabbe, BJ, Gabriel, SE, Gakidou, E, Ganatra, HA, Garcia, B, Gaspari, F, Gillum, RF, Gmel, G, Gonzalez-Medina, D, Gosselin, R, Grainger, R, Grant, B, Groeger, J, Guillemin, F, Gunnell, D, Gupta, R, Haagsma, J, Hagan, H, Halasa, YA, Hall, W, Haring, D, Haro, JM, Harrison, JE, Havmoeller, R, Hay, RJ, Higashi, H, Hill, C, Hoen, B, Hoffman, H, Hotez, PJ, Hoy, D, Huang, JJ, Ibeanusi, SE, Jacobsen, KH, James, SL, Jarvis, D, Jasrasaria, R, Jayaraman, S, Johns, N, Jonas, JB, Karthikeyan, G, Kassebaum, N, Kawakami, N, Keren, A, Khoo, JP, King, CH, Knowlton, LM, Kobusingye, O, Koranteng, A, Krishnamurthi, R, Laden, F, Lalloo, R, Laslett, LL, Lathlean, T, Leasher, JL, Lee, YY, Leigh, J, Levinson, D, Lim, SS, Limb, E, Lin, JK, Lipnick, M, Lipshultz, SE, Liu, W, Loane, M, Ohno, SL, Lyons, R, Mabweijano, J, MacIntyre, MF, Malekzadeh, R, Mallinger, L, Manivannan, S, Marcenes, W, March, L, Margolis, DJ, Marks, GB, Marks, R, Matsumori, A, Matzopoulos, R, Mayosi, BM, McAnulty, JH, McDermott, MM, McGill, N, McGrath, J, Medina-Mora, ME, Meltzer, M, Mensah, GA, Merriman, TR, Meyer, AC, Miglioli, V, Miller, M, Miller, TR, Mitchell, PB, Mock, C, Mocumbi, AO, Moffitt, TE, Mokdad, AA, Monasta, L, Montico, M, Moradi-Lakeh, M, Moran, A, Morawska, L, Mori, R, Murdoch, ME, Mwaniki, MK, Naidoo, K, Nair, MN, Naldi, L, Narayan, KM, Nelson, PK, Nelson, RG, Nevitt, MC, Newton, CR, Nolte, S, Norman, P, Norman, R, O'Donnell, M, O'Hanlon, S, Olives, C, Omer, SB, Ortblad, K, Osborne, R, Ozgediz, D, Page, A, Pahari, B, Pandian, JD, Rivero, AP, Patten, SB, Pearce, N, Padilla, RP, Perez-Ruiz, F, Perico, N, Pesudovs, K, Phillips, D, Phillips, MR, Pierce, K, Pion, S, Polanczyk, GV, Polinder, S, Pope, CA III, Popova, S, Porrini, E, Pourmalek, F, Prince, M, Pullan, RL, Ramaiah, KD, Ranganathan, D, Razavi, H, Regan, M, Rehm, JT, Rein, DB, Remuzzi, G, Richardson, K, Rivara, FP, Roberts, T, Robinson, C, De Leon, FR, Ronfani, L, Room, R, Rosenfeld, LC, Rushton, L, Sacco, RL, Saha, S, Sampson, U, Sanchez-Riera, L, Sanman, E, Schwebel, DC, Scott, JG, Segui-Gomez, M, Shahraz, S, Shepard, DS, Shin, H, Shivakoti, R, Singh, D, Singh, GM, Singh, JA, Singleton, J, Sleet, DA, Sliwa, K, Smith, E, Smith, JL, Stapelberg, NJ, Steer, A, Steiner, T, Stolk, WA, Stovner, LJ, Sudfeld, C, Syed, S, Tamburlini, G, Tavakkoli, M, Taylor, HR, Taylor, JA, Taylor, WJ, Thomas, B, Thomson, WM, Thurston, GD, Tleyjeh, IM, Tonelli, M, Towbin, JA, Truelsen, T, Tsilimbaris, MK, Ubeda, C, Undurraga, EA, van der Werf, MJ, van Os, J, Vavilala, MS, Venketasubramanian, N, Wang, M, Wang, W, Watt, K, Weatherall, DJ, Weinstock, MA, Weintraub, R, Weisskopf, MG, Weissman, MM, White, RA, Whiteford, H, Wiebe, N, Wiersma, ST, Wilkinson, JD, Williams, HC, Williams, SR, Witt, E, Wolfe, F, Woolf, AD, Wulf, S, Yeh, PH, Zaidi, AK, Zheng, ZJ, Zonies, D, Lopez, AD, AlMazroa, MA, Memish, ZA (2012). Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 21972223.
Na, KS, Chang, HS, Won, E, Han, KM, Choi, S, Tae, WS, Yoon, HK, Kim, YK, Joe, SH, Jung, IK, Lee, MS, Ham, BJ (2014). Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder. PLOS ONE 9, e85425.
Nair, A, Howard, R (2013). ENCODE and a new landscape for psychiatric genetics. British Journal of Psychiatry 203, 8485.
Nicolson, NA (2004). Childhood parental loss and cortisol levels in adult men. Psychoneuroendocrinology 29, 10121018.
Nivard, MG, Dolan, CV, Kendler, KS, Kan, KJ, Willemsen, G, van Beijsterveldt, CE, Lindauer, RJ, van Beek, JH, Geels, LM, Bartels, M, Middeldorp, CM, Boomsma, DI (2015). Stability in symptoms of anxiety and depression as a function of genotype and environment: a longitudinal twin study from ages 3 to 63 years. Psychological Medicine 45, 10391049.
Oberlander, TF, Weinberg, J, Papsdorf, M, Grunau, R, Misri, S, Devlin, AM (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics 3, 97106.
O'Toole, SM, Sekula, LK, Rubin, RT (1997). Pituitary–adrenal cortical axis measures as predictors of sustained remission in major depression. Biological Psychiatry 42, 8589.
Ou, JN, Torrisani, J, Unterberger, A, Provençal, N, Shikimi, K, Karimi, M, Ekstrom, TJ, Szyf, M (2007). Histone deacetylase inhibitor trichostatin A induces global and gene-specific DNA demethylation in human cancer cell lines. Biochemical Pharmacology 73, 12971307.
Pariante, CM (2006). The glucocorticoid receptor: part of the solution or part of the problem? Journal of Psychopharmacology 20, 7984.
Pariante, CM (2009). Risk factors for development of depression and psychosis. Glucocorticoid receptors and pituitary implications for treatment with antidepressant and glucocorticoids. Annals of the New York Academy of Sciences 1179, 144152.
Pariante, CM, Lightman, SL (2008). The HPA axis in major depression: classical theories and new developments. Trends in Neurosciences 31, 464468.
Pariante, CM, Miller, AH (2001). Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biological Psychiatry 49, 391404.
Pepin, MC, Pothier, F, Barden, N (1992). Antidepressant drug action in a transgenic mouse model of the endocrine changes seen in depression. Molecular Pharmacology 42, 991995.
Perroud, N, Paoloni-Giacobino, A, Prada, P, Olie, E, Salzmann, A, Nicastro, R, Guillaume, S, Mouthon, D, Stouder, C, Dieben, K, Huguelet, P, Courtet, P, Malafosse, A (2011). Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Translational Psychiatry 1, e59.
Plank, JL, Dean, A (2014). Enhancer function: mechanistic and genome-wide insights come together. Molecular Cell 55, 514.
Plessy, C, Desbois, L, Fujii, T, Carninci, P (2013). Population transcriptomics with single-cell resolution: a new field made possible by microfluidics: a technology for high throughput transcript counting and data-driven definition of cell types. BioEssays 35, 131140.
Power, RA, Keller, MC, Ripke, S, Abdellaoui, A, Wray, NR, Sullivan, PF, Group MPW, Breen, G (2014). A recessive genetic model and runs of homozygosity in major depressive disorder. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics 165B, 157166.
Provençal, N, Suderman, MJ, Guillemin, C, Massart, R, Ruggiero, A, Wang, D, Bennett, AJ, Pierre, PJ, Friedman, DP, Côté, SM, Hallett, M, Tremblay, RE, Suomi, SJ, Szyf, M (2012). The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells. Journal of Neuroscience 32, 1562615642.
Raadsheer, FC, Hoogendijk, WJ, Stam, FC, Tilders, FJ, Swaab, DF (1994). Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 60, 436444.
Radford, L, Corral, S, Bradley, C, Fisher, HL (2013). The prevalence and impact of child maltreatment and other types of victimization in the UK: findings from a population survey of caregivers, children and young people and young adults. Child Abuse and Neglect 37, 801813.
Radtke, KM, Ruf, M, Gunter, HM, Dohrmann, K, Schauer, M, Meyer, A, Elbert, T (2011). Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Translational Psychiatry 1, e21.
Razin, A, Riggs, AD (1980). DNA methylation and gene function. Science 210, 604610.
Reik, W (2007). Stability and flexibility of epigenetic gene regulation in mammalian development. Nature 447, 425432.
Reul, JM (2014). Making memories of stressful events: a journey along epigenetic, gene transcription, and signaling pathways. Frontiers in Psychiatry 5, 5.
Riggs, AD (1975). X inactivation, differentiation, and DNA methylation. Cytogenetics and Cell Genetics 14, 925.
Ripke, S, Wray, NR, Lewis, CM, Hamilton, SP, Weissman, MM, Breen, G, Byrne, EM, Blackwood, DH, Boomsma, DI, Cichon, S, Heath, AC, Holsboer, F, Lucae, S, Madden, PA, Martin, NG, McGuffin, P, Muglia, P, Noethen, MM, Penninx, BP, Pergadia, ML, Potash, JB, Rietschel, M, Lin, D, Muller-Myhsok, B, Shi, J, Steinberg, S, Grabe, HJ, Lichtenstein, P, Magnusson, P, Perlis, RH, Preisig, M, Smoller, JW, Stefansson, K, Uher, R, Kutalik, Z, Tansey, KE, Teumer, A, Viktorin, A, Barnes, MR, Bettecken, T, Binder, EB, Breuer, R, Castro, VM, Churchill, SE, Coryell, WH, Craddock, N, Craig, IW, Czamara, D, De Geus, EJ, Degenhardt, F, Farmer, AE, Fava, M, Frank, J, Gainer, VS, Gallagher, PJ, Gordon, SD, Goryachev, S, Gross, M, Guipponi, M, Henders, AK, Herms, S, Hickie, IB, Hoefels, S, Hoogendijk, W, Hottenga, JJ, Iosifescu, DV, Ising, M, Jones, I, Jones, L, Jung-Ying, T, Knowles, JA, Kohane, IS, Kohli, MA, Korszun, A, Landen, M, Lawson, WB, Lewis, G, Macintyre, D, Maier, W, Mattheisen, M, McGrath, PJ, McIntosh, A, McLean, A, Middeldorp, CM, Middleton, L, Montgomery, GM, Murphy, SN, Nauck, M, Nolen, WA, Nyholt, DR, O'Donovan, M, Oskarsson, H, Pedersen, N, Scheftner, WA, Schulz, A, Schulze, TG, Shyn, SI, Sigurdsson, E, Slager, SL, Smit, JH, Stefansson, H, Steffens, M, Thorgeirsson, T, Tozzi, F, Treutlein, J, Uhr, M, van den Oord, EJ, Van Grootheest, G, Volzke, H, Weilburg, JB, Willemsen, G, Zitman, FG, Neale, B, Daly, M, Levinson, DF, Sullivan, PF, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (2013). A mega-analysis of genome-wide association studies for major depressive disorder. Molecular Psychiatry 18, 497511.
Roberts, NJ, Vogelstein, JT, Parmigiani, G, Kinzler, KW, Vogelstein, B, Velculescu, VE (2012). The predictive capacity of personal genome sequencing. Science Translational Medicine 4, 133ra58.
Robinson, MD, Kahraman, A, Law, CW, Lindsay, H, Nowicka, M, Weber, LM, Zhou, X (2014). Statistical methods for detecting differentially methylated loci and regions. Frontiers in Genetics 5, 324.
Rollins, B, Martin, MV, Morgan, L, Vawter, MP (2010). Analysis of whole genome biomarker expression in blood and brain. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics 153B, 919936.
Rutter, M (1985). Resilience in the face of adversity. Protective factors and resistance to psychiatric disorder. British Journal of Psychiatry 147, 598611.
Sandhu, R, Roll, JD, Rivenbark, AG, Coleman, WB (2015). Dysregulation of the epigenome in human breast cancer: contributions of gene-specific DNA hypermethylation to breast cancer pathobiology and targeting the breast cancer methylome for improved therapy. American Journal of Pathology 185, 282292.
Schmidt, HD, Shelton, RC, Duman, RS (2011). Functional biomarkers of depression: diagnosis, treatment, and pathophysiology. Neuropsychopharmacology 36, 23752394.
Schneider, M, Engel, A, Fasching, PA, Haberle, L, Binder, EB, Voigt, F, Grimm, J, Faschingbauer, F, Eichler, A, Dammer, U, Rebhan, D, Amann, M, Raabe, E, Goecke, TW, Quast, C, Beckmann, MW, Kornhuber, J, Seifert, A, Burghaus, S (2014). Genetic variants in the genes of the stress hormone signalling pathway and depressive symptoms during and after pregnancy. Biomed Research International 2014, 469278.
Sharp, H, Pickles, A, Meaney, M, Marshall, K, Tibu, F, Hill, J (2012). Frequency of infant stroking reported by mothers moderates the effect of prenatal depression on infant behavioural and physiological outcomes. PLOS ONE 7, e45446.
Simar, D, Versteyhe, S, Donkin, I, Liu, J, Hesson, L, Nylander, V, Fossum, A, Barres, R (2014). DNA methylation is altered in B and NK lymphocytes in obese and type 2 diabetic human. Metabolism 63, 11881197.
Smith, ZD, Meissner, A (2013). DNA methylation: roles in mammalian development. Nature Reviews, Genetics 14, 204220.
Spijker, AT, van Rossum, EF (2012). Glucocorticoid sensitivity in mood disorders. Neuroendocrinology 95, 179186.
Suderman, M, McGowan, PO, Sasaki, A, Huang, TC, Hallett, MT, Meaney, MJ, Turecki, G, Szyf, M (2012). Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proceedings of the National Academy of Sciences of the USA 109 (Suppl. 2), 1726617272.
Sulistyoningrum, DC, Singh, R, Devlin, AM (2012). Epigenetic regulation of glucocorticoid receptor expression in aorta from mice with hyperhomocysteinemia. Epigenetics 7, 514521.
Sullivan, PF, Neale, MC, Kendler, KS (2000). Genetic epidemiology of major depression: review and meta-analysis. American Journal of Psychiatry 157, 15521562.
Sun, H, Kennedy, PJ, Nestler, EJ (2013). Epigenetics of the depressed brain: role of histone acetylation and methylation. Neuropsychopharmacology 38, 124137.
Sweatt, JD (2009). Experience-dependent epigenetic modifications in the central nervous system. Biological Psychiatry 65, 191197.
Szczepankiewicz, A, Leszczynska-Rodziewicz, A, Pawlak, J, Narozna, B, Rajewska-Rager, A, Wilkosc, M, Zaremba, D, Maciukiewicz, M, Twarowska-Hauser, J (2014). FKBP5 polymorphism is associated with major depression but not with bipolar disorder. Journal of Affective Disorders 164, 3337.
Turecki, G, Meaney, MJ (2014). Effects of the social environment and stress on glucocorticoid receptor gene methylation: a systematic review. Biological Psychiatry. Published online 13 December 2014. doi:10.1016/j.biopsych.2014.11.022.
Turner, JD, Alt, SR, Cao, L, Vernocchi, S, Trifonova, S, Battello, N, Muller, CP (2010). Transcriptional control of the glucocorticoid receptor: CpG islands, epigenetics and more. Biochemical Pharmacology 80, 18601868.
Turner, JD, Muller, CP (2005). Structure of the glucocorticoid receptor (NR3C1) gene 5′ untranslated region: identification, and tissue distribution of multiple new human exon 1. Journal of Molecular Endocrinology 35, 283292.
Turner, JD, Schote, AB, Macedo, JA, Pelascini, LP, Muller, CP (2006). Tissue specific glucocorticoid receptor expression, a role for alternative first exon usage? Biochemical Pharmacology 72, 15291537.
Turner, JD, Vernocchi, S, Schmitz, S, Muller, CP (2014). Role of the 5′-untranslated regions in post-transcriptional regulation of the human glucocorticoid receptor. Biochimica et Biophysica Acta 1839, 10511061.
Tylee, DS, Kawaguchi, DM, Glatt, SJ (2013). On the outside, looking in: a review and evaluation of the comparability of blood and brain ”-omes”. American Journal of Medical Genetics, Part B, Neuropsychiatric Genetics 162B, 595603.
Tyrka, AR, Price, LH, Marsit, C, Walters, OC, Carpenter, LL (2012). Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: preliminary findings in healthy adults. PLOS ONE 7, e30148.
Tyrka, AR, Wier, L, Price, LH, Ross, N, Anderson, GM, Wilkinson, CW, Carpenter, LL (2008). Childhood parental loss and adult hypothalamic–pituitary–adrenal function. Biological Psychiatry 63, 11471154.
Uchida, S, Nishida, A, Hara, K, Kamemoto, T, Suetsugi, M, Fujimoto, M, Watanuki, T, Wakabayashi, Y, Otsuki, K, McEwen, BS, Watanabe, Y (2008). Characterization of the vulnerability to repeated stress in Fischer 344 rats: possible involvement of microRNA-mediated down-regulation of the glucocorticoid receptor. European Journal of Neuroscience 27, 22502261.
Uher, R (2014). Gene–environment interactions in common mental disorders: an update and strategy for a genome-wide search. Social Psychiatry and Psychiatric Epidemiology 49, 314.
Wang, Q, Verweij, EW, Krugers, HJ, Joels, M, Swaab, DF, Lucassen, PJ (2014). Distribution of the glucocorticoid receptor in the human amygdala; changes in mood disorder patients. Brain Structure and Function 219, 16151626.
Watson, S, Owen, BM, Gallagher, P, Hearn, AJ, Young, AH, Ferrier, IN (2007). Family history, early adversity and the hypothalamic–pituitary–adrenal (HPA) axis: mediation of the vulnerability to mood disorders. Neuropsychiatric Disease and Treatment 3, 647653.
Weaver, IC, Cervoni, N, Champagne, FA, D'Alessio, AC, Sharma, S, Seckl, JR, Dymov, S, Szyf, M, Meaney, MJ (2004). Epigenetic programming by maternal behavior. Nature Neuroscience 7, 847854.
Weaver, IC, D'Alessio, AC, Brown, SE, Hellstrom, IC, Dymov, S, Sharma, S, Szyf, M, Meaney, MJ (2007). The transcription factor nerve growth factor-inducible protein A mediates epigenetic programming: altering epigenetic marks by immediate-early genes. Journal of Neuroscience 27, 17561768.
Webster, MJ, Knable, MB, O'Grady, J, Orthmann, J, Weickert, CS (2002). Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Molecular Psychiatry 7, 985994, 924.
Widom, CS, DuMont, K, Czaja, SJ (2007). A prospective investigation of major depressive disorder and comorbidity in abused and neglected children grown up. Archives of General Psychiatry 64, 4956.
Wildeman, C, Emanuel, N, Leventhal, JM, Putnam-Hornstein, E, Waldfogel, J, Lee, H (2014). The prevalence of confirmed maltreatment among US children, 2004 to 2011. JAMA Pediatrics 168, 706713.
Wong, CC, Meaburn, EL, Ronald, A, Price, TS, Jeffries, AR, Schalkwyk, LC, Plomin, R, Mill, J (2014). Methylomic analysis of monozygotic twins discordant for autism spectrum disorder and related behavioural traits. Molecular Psychiatry 19, 495503.
Wood, AR, Esko, T, Yang, J, Vedantam, S, Pers, TH, Gustafsson, S, Chu, AY, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, ML, Croteau-Chonka, DC, Day, FR, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, AU, Karjalainen, J, Lo, KS, Locke, AE, Magi, R, Mihailov, E, Porcu, E, Randall, JC, Scherag, A, Vinkhuyzen, AA, Westra, HJ, Winkler, TW, Workalemahu, T, Zhao, JH, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, GB, Feenstra, B, Feitosa, MF, Fischer, K, Fraser, RM, Goel, A, Gong, J, Justice, AE, Kanoni, S, Kleber, ME, Kristiansson, K, Lim, U, Lotay, V, Lui, JC, Mangino, M, Mateo Leach, I, Medina-Gomez, C, Nalls, MA, Nyholt, DR, Palmer, CD, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, JS, Ripke, S, Shungin, D, Stancakova, A, Strawbridge, RJ, Sung, YJ, Tanaka, T, Teumer, A, Trompet, S, van der Laan, SW, van Setten, J, Van Vliet-Ostaptchouk, JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlov, J, Arscott, GM, Bandinelli, S, Barrett, A, Bellis, C, Bennett, AJ, Berne, C, Bluher, M, Bolton, JL, Bottcher, Y, Boyd, HA, Bruinenberg, M, Buckley, BM, Buyske, S, Caspersen, IH, Chines, PS, Clarke, R, Claudi-Boehm, S, Cooper, M, Daw, EW, De Jong, PA, Deelen, J, Delgado, G, Denny, JC, Dhonukshe-Rutten, R, Dimitriou, M, Doney, AS, Dorr, M, Eklund, N, Eury, E, Folkersen, L, Garcia, ME, Geller, F, Giedraitis, V, Go, AS, Grallert, H, Grammer, TB, Grassler, J, Gronberg, H, de Groot, LC, Groves, CJ, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hannemann, A, Hartman, CA, Hassinen, M, Hayward, C, Heard-Costa, NL, Helmer, Q, Hemani, G, Henders, AK, Hillege, HL, Hlatky, MA, Hoffmann, W, Hoffmann, P, Holmen, O, Houwing-Duistermaat, JJ, Illig, T, Isaacs, A, James, AL, Jeff, J, Johansen, B, Johansson, A, Jolley, J, Juliusdottir, T, Junttila, J, Kho, AN, Kinnunen, L, Klopp, N, Kocher, T, Kratzer, W, Lichtner, P, Lind, L, Lindstrom, J, Lobbens, S, Lorentzon, M, Lu, Y, Lyssenko, V, Magnusson, PK, Mahajan, A, Maillard, M, McArdle, WL, McKenzie, CA, McLachlan, S, McLaren, PJ, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, KL, Morken, MA, Muller, G, Muller-Nurasyid, M, Musk, AW, Narisu, N, Nauck, M, Nolte, IM, Nothen, MM, Oozageer, L, Pilz, S, Rayner, NW, Renstrom, F, Robertson, NR, Rose, LM, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, FR, Schunkert, H, Scott, RA, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, JH, Smith, AV, Smolonska, J, Stanton, AV, Stirrups, K, Stott, DJ, Stringham, HM, Sundstrom, J, Swertz, MA, Syvanen, AC, Tayo, BO, Thorleifsson, G, Tyrer, JP, van Dijk, S, van Schoor, NM, van der Velde, N, van Heemst, D, van Oort, FV, Vermeulen, SH, Verweij, N, Vonk, JM, Waite, LL, Waldenberger, M, Wennauer, R, Wilkens, LR, Willenborg, C, Wilsgaard, T, Wojczynski, MK, Wong, A, Wright, AF, Zhang, Q, Arveiler, D, Bakker, SJ, Beilby, J, Bergman, RN, Bergmann, S, Biffar, R, Blangero, J, Boomsma, DI, Bornstein, SR, Bovet, P, Brambilla, P, Brown, MJ, Campbell, H, Caulfield, MJ, Chakravarti, A, Collins, R, Collins, FS, Crawford, DC, Cupples, LA, Danesh, J, de Faire, U, den Ruijter, HM, Erbel, R, Erdmann, J, Eriksson, JG, Farrall, M, Ferrannini, E, Ferrieres, J, Ford, I, Forouhi, NG, Forrester, T, Gansevoort, RT, Gejman, PV, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, DW, Hall, AS, Harris, TB, Hattersley, AT, Heath, AC, Hengstenberg, C, Hicks, AA, Hindorff, LA, Hingorani, AD, Hofman, A, Hovingh, GK, Humphries, SE, Hunt, SC, Hypponen, E, Jacobs, KB, Jarvelin, MR, Jousilahti, P, Jula, AM, Kaprio, J, Kastelein, JJ, Kayser, M, Kee, F, Keinanen-Kiukaanniemi, SM, Kiemeney, LA, Kooner, JS, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, AT, Kumari, M, Kuusisto, J, Lakka, TA, Langenberg, C, Le Marchand, L, Lehtimaki, T, Lupoli, S, Madden, PA, Mannisto, S, Manunta, P, Marette, A, Matise, TC, McKnight, B, Meitinger, T, Moll, FL, Montgomery, GW, Morris, AD, Morris, AP, Murray, JC, Nelis, M, Ohlsson, C, Oldehinkel, AJ, Ong, KK, Ouwehand, WH, Pasterkamp, G, Peters, A, Pramstaller, PP, Price, JF, Qi, L, Raitakari, OT, Rankinen, T, Rao, DC, Rice, TK, Ritchie, M, Rudan, I, Salomaa, V, Samani, NJ, Saramies, J, Sarzynski, MA, Schwarz, PE, Sebert, S, Sever, P, Shuldiner, AR, Sinisalo, J, Steinthorsdottir, V, Stolk, RP, Tardif, JC, Tonjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, MC, Electronic Medical, R, Genomics, C, Consortium, MI, Consortium, P, LifeLines Cohort, S, Amouyel, P, Asselbergs, FW, Assimes, TL, Bochud, M, Boehm, BO, Boerwinkle, E, Bottinger, EP, Bouchard, C, Cauchi, S, Chambers, JC, Chanock, SJ, Cooper, RS, de Bakker, PI, Dedoussis, G, Ferrucci, L, Franks, PW, Froguel, P, Groop, LC, Haiman, CA, Hamsten, A, Hayes, MG, Hui, J, Hunter, DJ, Hveem, K, Jukema, JW, Kaplan, RC, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, NG, Marz, W, Melbye, M, Moebus, S, Munroe, PB, Njolstad, I, Oostra, BA, Palmer, CN, Pedersen, NL, Perola, M, Perusse, L, Peters, U, Powell, JE, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, PM, Rivadeneira, F, Rotter, JI, Saaristo, TE, Saleheen, D, Schlessinger, D, Slagboom, PE, Snieder, H, Spector, TD, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Volzke, H, Walker, M, Wareham, NJ, Watkins, H, Wichmann, HE, Wilson, JF, Zanen, P, Deloukas, P, Heid, IM, Lindgren, CM, Mohlke, KL, Speliotes, EK, Thorsteinsdottir, U, Barroso, I, Fox, CS, North, KE, Strachan, DP, Beckmann, JS, Berndt, SI, Boehnke, M, Borecki, IB, McCarthy, MI, Metspalu, A, Stefansson, K, Uitterlinden, AG, van Duijn, CM, Franke, L, Willer, CJ, Price, AL, Lettre, G, Loos, RJ, Weedon, MN, Ingelsson, E, O'Connell, JR, Abecasis, GR, Chasman, DI, Goddard, ME, Visscher, PM, Hirschhorn, JN, Frayling, TM (2014). Defining the role of common variation in the genomic and biological architecture of adult human height. Nature Genetics 46, 11731186.
World Health Organization (2008). Global Burden of Disease Report (http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html). Accessed 15 July 2015.
Yau, JL, Hibberd, C, Noble, J, Seckl, JR (2002). The effect of chronic fluoxetine treatment on brain corticosteroid receptor mRNA expression and spatial memory in young and aged rats. Brain Research, Molecular Brain Research 106, 117123.
Yehuda, R, Boisoneau, D, Mason, JW, Giller, EL (1993). Glucocorticoid receptor number and cortisol excretion in mood, anxiety, and psychotic disorders. Biological Psychiatry 34, 1825.
Young, AH (2004). Cortisol in mood disorders. Stress 7, 205208.
Zannas, AS, Provençal, N, Binder, EB (2015). Epigenetics of posttraumatic stress disorder: current evidence, challenges, and future directions. Biological Psychiatry 78, 327335.
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Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
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