Hostname: page-component-cd9895bd7-hc48f Total loading time: 0 Render date: 2024-12-27T09:08:20.445Z Has data issue: false hasContentIssue false

Increased serotonin transporter gene (SERT) DNA methylation is associated with bullying victimization and blunted cortisol response to stress in childhood: a longitudinal study of discordant monozygotic twins

Published online by Cambridge University Press:  10 December 2012

I. Ouellet-Morin
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK School of Criminology, Université de Montréal, Mental Health Institute of Montréal Research Center and the Research Group on Child Maladjustment, Canada
C. C. Y. Wong
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
A. Danese
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK Department of Child and Adolescent Psychiatry, Institute of Psychiatry, King's College London, London, UK
C. M. Pariante
Affiliation:
Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK
A. S. Papadopoulos
Affiliation:
Section of Neurobiology of Mood Disorders, Institute of Psychiatry, King's College London, London, UK Affective Disorders Unit Laboratory, National Affective Disorders Unit, Bethlem Royal Hospital, Beckenham, Kent, UK
J. Mill
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
L. Arseneault*
Affiliation:
MRC Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, UK
*
*Address for correspondence: L. Arseneault, Ph.D., MRC SGDP Centre, Institute of Psychiatry, King's College London, London SE5 8AF, UK. (Email: louise.arseneault@kcl.ac.uk)

Abstract

Background

Childhood adverse experiences are known to induce persistent changes in the hypothalamic–pituitary–adrenal (HPA) axis reactivity to stress. However, the mechanisms by which these experiences shape the neuroendocrine response to stress remain unclear.

Method

We tested whether bullying victimization influenced serotonin transporter gene (SERT) DNA methylation using a discordant monozygotic (MZ) twin design. A subsample of 28 MZ twin pairs discordant for bullying victimization, with data on cortisol and DNA methylation, were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994–1995 cohort of families with twins.

Results

Bullied twins had higher SERT DNA methylation at the age of 10 years compared with their non-bullied MZ co-twins. This group difference cannot be attributed to the children's genetic makeup or their shared familial environments because of the study design. Bullied twins also showed increasing methylation levels between the age of 5 years, prior to bullying victimization, and the age of 10 years whereas no such increase was detected in non-bullied twins across time. Moreover, children with higher SERT methylation levels had blunted cortisol responses to stress.

Conclusions

Our study extends findings drawn from animal models, supports the hypothesis that early-life stress modifies DNA methylation at a specific cytosine–phosphate–guanine (CpG) site in the SERT promoter and HPA functioning and suggests that these two systems may be functionally associated.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2012 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Alexander, N, Kuepper, Y, Schmitz, A, Osinsky, R, Kozyra, E, Hennig, J (2009). Gene–environment interactions predict cortisol responses after acute stress: implications for the etiology of depression. Psychoneuroendocrinology 34, 12941303.CrossRefGoogle ScholarPubMed
Arseneault, L, Bowes, L, Shakoor, S (2010). Bullying victimization in youths and mental health problems: ‘Much ado about nothing’? Psychological Medicine 40, 717729.CrossRefGoogle ScholarPubMed
Arseneault, L, Cannon, M, Fisher, HL, Polanczyk, G, Moffitt, TE, Caspi, A (2011). Childhood trauma and children's emerging psychotic symptoms: a genetically sensitive longitudinal cohort study. American Journal of Psychiatry 168, 6572.CrossRefGoogle ScholarPubMed
Bagot, RC, Meaney, MJ (2010). Epigenetics and the biological basis of gene x environment interactions. Journal of the American Academy of Child and Adolescent Psychiatry 49, 752771.CrossRefGoogle ScholarPubMed
Bakermans-Kranenburg, MJ, van IJzendoorn, MH (2009). The first 10,000 Adult Attachment Interviews: distributions of adult attachment representations in clinical and non-clinical groups. Attachment and Human Development 11, 223263.CrossRefGoogle Scholar
Ball, HA, Arseneault, L, Taylor, A, Maughan, B, Caspi, A, Moffitt, TE (2008). Genetic and environmental influences on victims, bullies and bully-victims in childhood. Journal of Child Psychology and Psychiatry 49, 104112.CrossRefGoogle ScholarPubMed
Beach, SR, Brody, GH, Todorov, AA, Gunter, TD, Philibert, RA (2010). Methylation at SLC6A4 is linked to family history of child abuse: an examination of the Iowa Adoptee sample. American Journal of Medical Genetics: Part B Neuropsychiatric Genetics 153B, 710713.Google ScholarPubMed
Beach, SR, Brody, GH, Todorov, AA, Gunter, TD, Philibert, RA (2011). Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: an examination of the Iowa adoptee sample. Psychosomatic Medicine 73, 8387.CrossRefGoogle ScholarPubMed
Bouma, E, Riese, H, Nederhof, E, Ormel, J, Oldehinkel, A (2010). No replication of genotype effect of 5-HTTLPR on cortisol response to social stress in larger adolescent sample. Biological Psychiatry 68, e33e34.CrossRefGoogle ScholarPubMed
Bruce, J, Fisher, PA, Pears, KC, Levine, S (2009). Morning cortisol levels in preschool-aged foster children: differential effects of maltreatment type. Developmental Psychobiology 51, 1423.CrossRefGoogle ScholarPubMed
Buske-Kirschbaum, A, Jobst, S, Wustmans, A, Kirschbaum, C, Rauh, W, Hellhammer, D (1997). Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosomatic Medicine 59, 419426.CrossRefGoogle ScholarPubMed
Byun, HM, Siegmund, KD, Pan, F, Weisenberger, DJ, Kanel, G, Laird, PW, Yang, AS (2009). Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Human Molecular Genetics 18, 48084817.CrossRefGoogle ScholarPubMed
Canli, T, Lesch, KP (2007). Long story short: the serotonin transporter in emotion regulation and social cognition. Nature Neuroscience 10, 11031109.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Caspi, A, Hariri, AR, Holmes, A, Uher, R, Moffitt, TE (2010). Genetic sensitivity to the environment: the case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry 167, 509527.CrossRefGoogle Scholar
Champagne, FA (2010). Epigenetic influence of social experiences across the lifespan. Developmental Psychobiology 52, 299311.CrossRefGoogle ScholarPubMed
Cicchetti, D, Rogosch, FA (2001). Diverse patterns of neuroendocrine activity in maltreated children. Development and Psychopatholgy 13, 677693.CrossRefGoogle ScholarPubMed
Coolen, MW, Statham, AL, Gardiner-Garden, M, Clark, SJ (2007). Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Research 35, e119.CrossRefGoogle ScholarPubMed
Devlin, AM, Brain, U, Austin, J, Oberlander, TF (2010). Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS One 5, e12201.CrossRefGoogle ScholarPubMed
Dickerson, SS, Kemeny, ME (2004). Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychological Bulletin 130, 355391.CrossRefGoogle ScholarPubMed
Dozier, M, Manni, M, Gordon, MK, Peloso, E, Gunnar, MR, Stovall-McClough, KC, Eldreth, D, Levine, S (2006). Foster children's diurnal production of cortisol: an exploratory study. Child Maltreatment 11, 189197.CrossRefGoogle ScholarPubMed
Dyche, G, Johnson, D (1991). Development and evaluation of CHIPASAT, an attentional test for children: II test–retest reliability and practice effect for a normal sample. Perceptual and Motor Skills 72, 563572.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Essex, MJ, Boyce, TW, Hertzman, C, Lam, LL, Armstrong, JM, Neumann, SM, Kobor, MS (2011). Epigenetic vestiges of early developmental adversity: childhood stress exposure and DNA methylation in adolescence. Child Development. Published online: 02 09 2011. doi:10.1111/j.1467-8624.2011.01641.x.Google ScholarPubMed
Fairchild, G, van Goozen, SH, Stollery, SJ, Brown, J, Gardiner, J, Herbert, J, Goodyer, IM (2008). Cortisol diurnal rhythm and stress reactivity in male adolescents with early-onset or adolescence-onset conduct disorder. Biological Psychiatry 64, 599606.CrossRefGoogle ScholarPubMed
Feder, A, Nestler, EJ, Charney, DS (2009). Psychobiology and molecular genetics of resilience. Nature Reviews Neuroscience 10, 446457.CrossRefGoogle ScholarPubMed
Feinberg, AP (2008). Epigenetics at the epicenter of modern medicine. Journal of the American Medical Association 299, 13451350.CrossRefGoogle ScholarPubMed
Filiberto, AC, Maccani, MA, Koestler, D, Wilhelm-Benartzi, C, Avissar-Whiting, M, Banister, CE, Gagne, LA, Marsit, CJ (2011). Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta. Epigenetics 6, 566572.CrossRefGoogle ScholarPubMed
Francis, DD, Champagne, FA, Liu, D, Meaney, MJ (1999). Maternal care, gene expression, and the development of individual differences in stress reactivity. Annals of the New York Academy of Sciences 896, 6684.CrossRefGoogle ScholarPubMed
Freeman, B, Smith, N, Curtis, C, Huckett, L, Mill, J, Craig, IW (2003). DNA from buccal swabs recruited by mail: evaluation of storage effects on long-term stability and suitability for multiplex polymerase chain reaction genotyping. Behavior Genetics 33, 6772.CrossRefGoogle ScholarPubMed
Fries, E, Hesse, J, Hellhammer, J, Hellhammer, DH (2005). A new view on hypocortisolism. Psychoneuroendocrinology 30, 10101016.CrossRefGoogle ScholarPubMed
Gotlib, IH, Joormann, J, Minor, KL, Hallmayer, J (2008). HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biological Psychiatry 63, 847851.CrossRefGoogle ScholarPubMed
Gunnar, MR, Vazquez, DM (2001). Low cortisol and a flattening of expected daytime rhythm: potential indices of risk in human development. Development and Psychopathology 13, 515538.CrossRefGoogle Scholar
Hariri, AR, Mattay, VS, Tessitore, A, Kolachana, B, Fera, F, Goldman, D, Egan, MF, Weinberger, DR (2002). Serotonin transporter genetic variation and the response of the human amygdala. Science 297, 400403.CrossRefGoogle ScholarPubMed
Heijmans, BT, Tobi, EW, Stein, AD, Putter, H, Blauw, GJ, Susser, ES, Slagboom, PE, Lumey, LH (2008). Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proceedings of the National Academy of Sciences USA 105, 1704617049.CrossRefGoogle ScholarPubMed
Heim, C, Ehlert, U, Hellhammer, DH (2000). The potential role of hypocortisolism in the pathophysiology of stress-related bodily disorders. Psychoneuroendocrinology 25, 135.CrossRefGoogle ScholarPubMed
Herman, JP, Cullinan, WE (1997). Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis. Trends in Neurosciences 20, 7884.CrossRefGoogle ScholarPubMed
Illingworth, R, Kerr, A, Desousa, D, Jorgensen, H, Ellis, P, Stalker, J, Jackson, D, Clee, C, Plumb, R, Rogers, J, Humphray, S, Cox, T, Langford, C, Bird, A (2008). A novel CpG island set identifies tissue-specific methylation at developmental gene loci. PLoS Biology 6, e22.CrossRefGoogle ScholarPubMed
Jirtle, RL, Skinner, MK (2007). Environmental epigenomics and disease susceptibility. Nature Reviews Genetics 8, 253262.CrossRefGoogle ScholarPubMed
Johnstone, SE, Baylin, SB (2010). Stress and the epigenetic landscape: a link to the pathobiology of human diseases? Nature Reviews Genetics 11, 806812.CrossRefGoogle Scholar
Kinnally, EL, Capitanio, JP, Leibel, R, Deng, L, Leduc, C, Haghighi, F, Mann, JJ (2010 a). Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes, Brain and Behavior 9, 575582.CrossRefGoogle ScholarPubMed
Kinnally, EL, Tarara, ER, Mason, WA, Mendoza, SP, Abel, K, Lyons, LA, Capitanio, JP (2010 b). Serotonin transporter expression is predicted by early life stress and is associated with disinhibited behavior in infant rhesus macaques. Genes, Brain and Behavior 9, 4552.CrossRefGoogle ScholarPubMed
Lesch, KP, Bengel, D, Heils, A, Sabol, SZ, Greenberg, BD, Petri, S, Benjamin, J, Muller, CR, Hamer, DH, Murphy, DL (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 15271531.CrossRefGoogle ScholarPubMed
Levine, S (2005). Developmental determinants of sensitivity and resistance to stress. Psychoneuroendocrinology 30, 939946.CrossRefGoogle ScholarPubMed
Li, Q, Wichems, C, Heils, A, Van De Kar, LD, Lesch, KP, Murphy, DL (1999). Reduction of 5-hydroxytryptamine (5-HT)1A-mediated temperature and neuroendocrine responses and 5-HT1A binding sites in 5-HT transporter knockout mice. Journal of Pharmacology and Experimental Therapeutics 291, 9991007.Google Scholar
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.CrossRefGoogle ScholarPubMed
Lowry, CA (2002). Functional subsets of serotonergic neurones: implications for control of the hypothalamic–pituitary–adrenal axis. Journal of Neuroendocrinology 14, 911923.CrossRefGoogle ScholarPubMed
Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience 10, 434445.CrossRefGoogle ScholarPubMed
McCrory, E, De Brito, SA, Viding, E (2010). Research review: the neurobiology and genetics of maltreatment and adversity. Journal of Child Psychology and Psychiatry 51, 10791095.CrossRefGoogle ScholarPubMed
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 Reviews Neuroscience 12, 342348.CrossRefGoogle ScholarPubMed
McGowan, PO, Szyf, M (2010). The epigenetics of social adversity in early life: implications for mental health outcomes. Neurobiology of Disease 39, 6672.CrossRefGoogle ScholarPubMed
Meaney, MJ (2010). Epigenetics and the biological definition of gene x environment interactions. Child Development 81, 4179.CrossRefGoogle ScholarPubMed
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 Neurosciences 7, 103123.CrossRefGoogle Scholar
Meewisse, ML, Reitsma, JB, de Vries, GJ, Gersons, BP, Olff, M (2007). Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis. British Journal of Psychiatry 191, 387392.CrossRefGoogle ScholarPubMed
Mill, J, Petronis, A (2007). Molecular studies of major depressive disorder: the epigenetic perspective. Molecular Psychiatry 12, 799814.CrossRefGoogle ScholarPubMed
Miller, GE, Chen, E, Zhou, ES (2007). If it goes up, must it come down? Chronic stress and the hypothalamic–pituitary–adrenocortical axis in humans. Psychological Bulletin 133, 2545.CrossRefGoogle ScholarPubMed
Miller, JM, Kinnally, EL, Ogden, RT, Oquendo, MA, Mann, JJ, Parsey, RV (2009). Reported childhood abuse is associated with low serotonin transporter binding in vivo in major depressive disorder. Synapse 63, 565573.CrossRefGoogle ScholarPubMed
Moffitt, TE; the E-Risk Study Team (2002). Teen-aged mothers in contemporary Britain. Journal of Child Psychology and Psychiatry 43, 727742.CrossRefGoogle ScholarPubMed
Mondelli, V, Dazzan, P, Hepgul, N, Di Forti, M, Aas, M, D'Albenzio, A, Di Nicola, M, Fisher, H, Handley, R, Marques, TR, Morgan, C, Navari, S, Taylor, H, Papadopoulos, A, Aitchison, KJ, Murray, RM, Pariante, CM (2010). Abnormal cortisol levels during the day and cortisol awakening response in first-episode psychosis: the role of stress and of antipsychotic treatment. Schizophrenia Research 116, 234242.CrossRefGoogle ScholarPubMed
Monteiro, J, Derom, C, Vlietinck, R, Kohn, N, Lesser, M, Gregersen, PK (1998). Commitment to X inactivation precedes the twinning event in monochorionic MZ twins. American Journal of Human Genetics 63, 339346.CrossRefGoogle Scholar
Mueller, A, Brocke, B, Fries, E, Lesch, KP, Kirschbaum, C (2010). The role of the serotonin transporter polymorphism for the endocrine stress response in newborns. Psychoneuroendocrinology 35, 289296.CrossRefGoogle ScholarPubMed
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 Reviews Neuroscience 12, 15591566.CrossRefGoogle ScholarPubMed
Naumova, OY, Lee, M, Koposov, R, Szyf, M, Dozier, M, Grigorenko, EL (2011). Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Development and Psychopathology 24, 143155.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Ochsner, KN, Gross, JJ (2005). The cognitive control of emotion. Trends in Cognitive Sciences 9, 242249.CrossRefGoogle ScholarPubMed
Olsson, CA, Foley, DL, Parkinson-Bates, M, Byrnes, G, McKenzie, M, Patton, GC, Morley, R, Anney, RJ, Craig, JM, Saffery, R (2010). Prospects for epigenetic research within cohort studies of psychological disorder: a pilot investigation of a peripheral cell marker of epigenetic risk for depression. Biological Psychology 83, 159165.CrossRefGoogle ScholarPubMed
Ouellet-Morin, I, Danese, A, Bowes, L, Shakoor, S, Ambler, A, Pariante, C, Papadopoulos, A, Caspi, A, Moffitt, TE, Arseneault, L (2011 a). A discordant MZ twin design shows blunted cortisol reactivity among bullied children. Journal of the American Academy of Child and Adolescent Psychiatry 50, 574582.CrossRefGoogle ScholarPubMed
Ouellet-Morin, I, Odgers, C, Danese, A, Bowes, L, Shakoor, S, Papadopoulos, A, Caspi, A, Moffitt, TE, Arseneault, L (2011 b). Blunted cortisol responses to stress signal social and behavioral problems among maltreated/bullied 12 year-old children. Biological Psychiatry 70, 10161023.CrossRefGoogle Scholar
Pezawas, L, Meyer-Lindenberg, A, Drabant, EM, Verchinski, BA, Munoz, KE, Kolachana, BS, Egan, MF, Mattay, VS, Hariri, AR, Weinberger, DR (2005). 5-HTTLPR polymorphism impacts human cingulate–amygdala interactions: a genetic susceptibility mechanism for depression. Nature Neuroscience 8, 828834.CrossRefGoogle ScholarPubMed
Philibert, RA, Sandhu, H, Hollenbeck, N, Gunter, T, Adams, W, Madan, A (2008). The relationship of 5HTT (SLC6A4) methylation and genotype on mRNA expression and liability to major depression and alcohol dependence in subjects from the Iowa Adoption Studies. American Journal of Medical Genetics: Part B Neuropsychiatric Genetics 147B, 543549.Google ScholarPubMed
Price, TS, Freeman, B, Craig, I, Petrill, SA, Ebersole, L, Plomin, R (2000). Infant zygosity can be assigned by parental report questionnaire data. Twin Research 3, 129133.CrossRefGoogle ScholarPubMed
Pruessner, JC, Kirschbaum, C, Meinlschmid, G, Hellhammer, DH (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28, 916931.CrossRefGoogle ScholarPubMed
Rakyan, VK, Down, TA, Balding, DJ, Beck, S (2011). Epigenome-wide association studies for common human diseases. Nature Reviews Genetics 12, 529541.CrossRefGoogle ScholarPubMed
Rakyan, VK, Down, TA, Thorne, NP, Flicek, P, Kulesha, E, Graf, S, Tomazou, EM, Backdahl, L, Johnson, N, Herberth, M, Howe, KL, Jackson, DK, Miretti, MM, Fiegler, H, Marioni, JC, Birney, E, Hubbard, TJ, Carter, NP, Tavare, S, Beck, S (2008). An integrated resource for genome-wide identification and analysis of human tissue-specific differentially methylated regions (tDMRs). Genome Research 18, 15181529.CrossRefGoogle ScholarPubMed
Rosa, A, Picchioni, MM, Kalidindi, S, Loat, CS, Knight, J, Toulopoulou, T, Vonk, R, van der Schot, AC, Nolen, W, Kahn, RS, McGuffin, P, Murray, RM, Craig, IW (2008). Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins. American Journal of Medical Genetics: Part B Neuropsychiatric Genetics 147B, 459462.Google ScholarPubMed
Roth, TL, Lubin, FD, Funk, AJ, Sweatt, JD (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biological Psychiatry 65, 760769.CrossRefGoogle ScholarPubMed
Rutter, M (2009). Epidemiological methods to tackle causal questions. International Journal of Epidemiology 38, 36.CrossRefGoogle ScholarPubMed
Sanchez, MM (2006). The impact of early adverse care on HPA axis development: nonhuman primate models. Hormones and Behavior 50, 623631.CrossRefGoogle ScholarPubMed
Shakoor, S, Jaffee, SR, Andreou, P, Bowes, L, Ambler, AP, Caspi, A, Moffitt, TE, Arseneault, L (2011). Mothers and children as informants of bullying victimization: results from an epidemiological cohort of children. Journal of Abnormal Child Psychology 39, 379387.CrossRefGoogle ScholarPubMed
Suomi, SJ (1997). Early determinants of behaviour: evidence from primate studies. British Medical Bulletin 53, 170184.CrossRefGoogle ScholarPubMed
Susman, EJ (2006). Psychobiology of persistent antisocial behavior: stress, early vulnerabilities and the attenuation hypothesis. Neuroscience and Biobehavioral Reviews 30, 376389.CrossRefGoogle ScholarPubMed
Talens, RP, Boomsma, DI, Tobi, EW, Kremer, D, Jukema, JW, Willemsen, G, Putter, H, Slagboom, PE, Heijmans, BT (2010). Variation, patterns, and temporal stability of DNA methylation: considerations for epigenetic epidemiology. Federation of the American Societies for Experimental Biology 24, 31353144.CrossRefGoogle ScholarPubMed
Tarullo, AR, Gunnar, MR (2006). Child maltreatment and the developing HPA axis. Hormone and Behavior 50, 632639.CrossRefGoogle ScholarPubMed
Tobi, EW, Lumey, LH, Talens, RP, Kremer, D, Putter, H, Stein, AD, Slagboom, PE, Heijmans, BT (2009). DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Human Molecular Genetics 18, 40464053.CrossRefGoogle ScholarPubMed
Tsankova, N, Renthal, W, Kumar, A, Nestler, EJ (2007). Epigenetic regulation in psychiatric disorders. Nature Reviews Neuroscience 8, 355367.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Uher, R, McGuffin, P (2010). The moderation by the serotonin transporter gene of environmental adversity in the etiology of depression: 2009 update. Molecular Psychiatry 15, 1822.CrossRefGoogle ScholarPubMed
van Goozen, SH, Fairchild, G, Snoek, H, Harold, GT (2007). The evidence for a neurobiological model of childhood antisocial behavior. Psychological Bulletin 133, 149182.CrossRefGoogle ScholarPubMed
Vazquez, DM, Neal, CR Jr., Patel, PD, Kaciroti, N, Lopez, JF (2012). Regulation of corticoid and serotonin receptor brain system following early life exposure of glucocorticoids: long term implications for the neurobiology of mood. Psychoneuroendocrinology 37, 421437.CrossRefGoogle ScholarPubMed
Vielhaber, K, Riemann, D, Feige, B, Kuelz, A, Kirschbaum, C, Voderholzer, U (2005). Impact of experimentally induced serotonin deficiency by tryptophan depletion on saliva cortisol concentrations. Pharmacopsychiatry 38, 8794.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Williams, RL (2000). A note on robust variance estimation for cluster-correlated data. Biometrics 56, 645646.CrossRefGoogle ScholarPubMed
Wong, CC, Caspi, A, Williams, B, Craig, IW, Houts, R, Ambler, A, Moffitt, TE, Mill, J (2010). A longitudinal study of epigenetic variation in twins. Epigenetics 5, 516526.CrossRefGoogle ScholarPubMed
Yehuda, R, Flory, JD, Pratchett, LC, Buxbaum, J, Ising, M, Holsboer, F (2010). Putative biological mechanisms for the association between early life adversity and the subsequent development of PTSD. Psychopharmacology 212, 405417.CrossRefGoogle ScholarPubMed
Supplementary material: PDF

Ouellet-Morin Supplementary Material

Appendix

Download Ouellet-Morin Supplementary Material(PDF)
PDF 96.2 KB