Child maltreatment and mental disorders – the role of epigenetics
Keywords:Child abuse, domestic violence, epigenesis, genetic, mental disorders
Introduction: Child maltreatment is associated with high risk for various physical and mental disorders and is associated with over 30% of adult psychopathology. Child maltreatment also relates with poor clinical outcomes, such as chronic disease, increased hospitalization, comorbidity and reduced response to treatment. Early adverse experiences can cause epigenetic changes, altering gene expression without changing DNA sequence. Epigenetic alterations in genes implicated in stress response and neurodevelopment might explain to some extent the impact of child maltreatment in mental health.
Objectives: Review available literature concerning the impact of child maltreatment in human epigenome, focusing on mental health related outcomes.
Development: DNA methylation induced by child maltreatment changes specific genes, in peripheral and brain tissues, producing major consequences in stress regulation, neural plasticity, and neurodevelopment. Methylation of the glucocorticoid receptor gene is one of the most studied epigenetic alterations that have been related to childhood maltreatment and seems to be responsible for an increased vulnerability to develop psychopathology. Epigenetic changes may not be permanent, and there are some interventions that seem to reduce DNA methylation. Therefore, in the future, DNA methylation may be used, not only in the diagnosis and prediction of treatment response, but also for therapeutic innovation.
Conclusions: Epigenetic changes can potentially explain pathophysiological changes related to child maltreatment exposure, may serve as biomarkers in stress-related disorders and provide targets for the development of new therapeutic and preventive interventions for individuals that were exposed to child abuse.
Cecil CA, Smith RG, Walton E, Mill J, McCrory EJ, Viding E. Epigenetic signatures of childhood abuse and neglect: Implications for psychiatric vulnerability. J Psychiatr Res. 2016;83:184-94.
Tyrka AR, Ridout KK, Parade SH. Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults. Dev Psychopathol. 2016;28(4pt2):1319-31.
Pollak SD. Multilevel developmental approaches to understanding the effects of child maltreatment: Recent advances and future challenges. Dev Psychopathol. 2015;27(4 Pt 2):1387-97.
Lutz PE, Turecki G. DNA methylation and childhood maltreatment: from animal models to human studies. Neuroscience. 2014;264:142-56.
Lutz PE, Almeida D, Fiori LM, Turecki G. Childhood maltreatment and stress-related psychopathology: the epigenetic memory hypothesis. Curr Pharm Des. 2015;21(11):1413-7.
Schury K, Kolassa IT. Biological memory of childhood maltreatment: current knowledge and recommendations for future research. Ann N Y Acad Sci. 2012;1262:93-100.
Cicchetti D, Hetzel S, Rogosch FA, Handley ED, Toth SL. An investigation of child maltreatment and epigenetic mechanisms of mental and physical health risk. Dev Psychopathol. 2016;28(4pt2):1305-17.
Nugent NR, Goldberg A, Uddin M. Topical Review: The Emerging Field of Epigenetics: Informing Models of Pediatric Trauma and Physical Health. J Pediatr Psychol. 2016;41(1):55-64.
Romens SE, McDonald J, Svaren J, Pollak SD. Associations between early life stress and gene methylation in children. Child Dev. 2015;86(1):303-9.
Weder N, Zhang H, Jensen K, Yang BZ, Simen A, Jackowski A, et al. Child abuse, depression, and methylation in genes involved with stress, neural plasticity, and brain circuitry. J Am Acad Child Adolesc Psychiatry. 2014;53(4):417-24.e5.
Bick J, Naumova O, Hunter S, Barbot B, Lee M, Luthar SS, et al. Childhood adversity and DNA methylation of genes involved in the hypothalamus-pituitary-adrenal axis and immune system: whole-genome and candidate-gene associations. Dev Psychopathol. 2012;24(4):1417-25.
Anacker C, O'Donnell KJ, Meaney MJ. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function. Dialogues Clin Neurosci. 2014;16(3):321-33.
Roth TL, Sweatt JD. Epigenetic marking of the BDNF gene by early-life adverse experiences. Horm Behav. 2011;59(3):315-20.
De Bellis MD, Zisk A. The biological effects of childhood trauma. Child Adolesc Psychiatr Clin N Am. 2014;23(2):185-222, vii.
Perroud N, Salzmann A, Prada P, Nicastro R, Hoeppli ME, Furrer S, et al. Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene. Transl Psychiatry. 2013;3:e207.
Menke A, Binder EB. Epigenetic alterations in depression and antidepressant treatment. Dialogues Clin Neurosci. 2014;16(3):395-404.
Smart C, Strathdee G, Watson S, Murgatroyd C, McAllister-Williams RH. Early life trauma, depression and the glucocorticoid receptor gene--an epigenetic perspective. Psychol Med. 2015;45(16):3393-410.
McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonte B, Szyf M, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009;12(3):342-8.
Beach SR, Brody GH, Todorov AA, Gunter TD, Philibert RA. Methylation at 5HTT mediates the impact of child sex abuse on women's antisocial behavior: an examination of the Iowa adoptee sample. Psychosom Med. 2011;73(1):83-7.
Perroud N, Paoloni-Giacobino A, Prada P, Olie E, Salzmann A, Nicastro R, et al. Increased methylation of glucocorticoid receptor gene (NR3C1) in adults with a history of childhood maltreatment: a link with the severity and type of trauma. Transl Psychiatry. 2011;1:e59.
Labonte B, Suderman M, Maussion G, Navaro L, Yerko V, Mahar I, et al. Genome-wide epigenetic regulation by early-life trauma. Arch Gen Psychiatry. 2012;69(7):722-31.
Tyrka AR, Price LH, Marsit C, Walters OC, Carpenter LL. Childhood adversity and epigenetic modulation of the leukocyte glucocorticoid receptor: preliminary findings in healthy adults. PLoS One. 2012;7(1):e30148.
Kang HJ, Kim JM, Stewart R, Kim SY, Bae KY, Kim SW, et al. Association of SLC6A4 methylation with early adversity, characteristics and outcomes in depression. Prog Neuropsychopharmacol Biol Psychiatry. 2013;44:23-8.
Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci. 2013;16(1):33-41.
Mehta D, Klengel T, Conneely KN, Smith AK, Altmann A, Pace TW, et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc Natl Acad Sci U S A. 2013;110(20):8302-7.
Zhang H, Wang F, Kranzler HR, Zhao H, Gelernter J. Profiling of childhood adversity-associated DNA methylation changes in alcoholic patients and healthy controls. PLoS One. 2013;8(6):e65648.
Thaler L, Gauvin L, Joober R, Groleau P, de Guzman R, Ambalavanan A, et al. Methylation of BDNF in women with bulimic eating syndromes: associations with childhood abuse and borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014;54:43-9.
van der Knaap LJ, Riese H, Hudziak JJ, Verbiest MM, Verhulst FC, Oldehinkel AJ, et al. Glucocorticoid receptor gene (NR3C1) methylation following stressful events between birth and adolescence. The TRAILS study. Transl Psychiatry. 2014;4:e381.
Radtke KM, Schauer M, Gunter HM, Ruf-Leuschner M, Sill J, Meyer A, et al. Epigenetic modifications of the glucocorticoid receptor gene are associated with the vulnerability to psychopathology in childhood maltreatment. Transl Psychiatry. 2015;5:e571.
Tyrka AR, Parade SH, Eslinger NM, Marsit CJ, Lesseur C, Armstrong DA, et al. Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children. Dev Psychopathol. 2015;27(2):577-85.
Unternaehrer E, Meyer AH, Burkhardt SC, Dempster E, Staehli S, Theill N, et al. Childhood maternal care is associated with DNA methylation of the genes for brain-derived neurotrophic factor (BDNF) and oxytocin receptor (OXTR) in peripheral blood cells in adult men and women. Stress. 2015;18(4):451-61.
Hecker T, Radtke KM, Hermenau K, Papassotiropoulos A, Elbert T. Associations among child abuse, mental health, and epigenetic modifications in the proopiomelanocortin gene (POMC): A study with children in Tanzania. Dev Psychopathol. 2016;28(4pt2):1401-12.
Smearman EL, Almli LM, Conneely KN, Brody GH, Sales JM, Bradley B, et al. Oxytocin Receptor Genetic and Epigenetic Variations: Association With Child Abuse and Adult Psychiatric Symptoms. Child Dev. 2016;87(1):122-34.
Provenzi L, Giorda R, Beri S, Montirosso R. SLC6A4 methylation as an epigenetic marker of life adversity exposures in humans: A systematic review of literature. Neurosci Biobehav Rev. 2016;71:7-20.
Booij L, Tremblay RE, Szyf M, Benkelfat C. Genetic and early environmental influences on the serotonin system: consequences for brain development and risk for psychopathology. J Psychiatry Neurosci. 2015;40(1):5-18.
Dong E, Chen Y, Gavin DP, Grayson DR, Guidotti A. Valproate induces DNA demethylation in nuclear extracts from adult mouse brain. Epigenetics. 2010;5(8):730-5.
Szyf M. The genome- and system-wide response of DNA methylation to early life adversity and its implication on mental health. Can J Psychiatry. 2013;58(12):697-704.
Dong E, Nelson M, Grayson DR, Costa E, Guidotti A. Clozapine and sulpiride but not haloperidol or olanzapine activate brain DNA demethylation. Proc Natl Acad Sci U S A. 2008;105(36):13614-9.
Tadic A, Muller-Engling L, Schlicht KF, Kotsiari A, Dreimuller N, Kleimann A, et al. Methylation of the promoter of brain-derived neurotrophic factor exon IV and antidepressant response in major depression. Mol Psychiatry. 2014;19(3):281-3.
Roberts S, Keers R, Lester KJ, Coleman JR, Breen G, Arendt K, et al. HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS. Depress Anxiety. 2015;32(12):861-70.
Yehuda R, Daskalakis NP, Desarnaud F, Makotkine I, Lehrner AL, Koch E, et al. Epigenetic Biomarkers as Predictors and Correlates of Symptom Improvement Following Psychotherapy in Combat Veterans with PTSD. Front Psychiatry. 2013;4:118.
Kashimoto RK, Toffoli LV, Manfredo MH, Volpini VL, Martins-Pinge MC, Pelosi GG, et al. Physical exercise affects the epigenetic programming of rat brain and modulates the adaptive response evoked by repeated restraint stress. Behav Brain Res. 2016;296:286-9.
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