Investigating epigenetic consequences of early-life adversity: some methodological considerations

Stressful and traumatic events occurring during early childhood have been consistently associated with the development of psychiatric disorders later in life. This relationship may be mediated in part by epigenetic mechanisms, such as DNA methylation, which are influenced by the early-life environment. Epigenetic patterns can have lifelong effects on gene expression and on the functioning of biological processes relevant to stress reactivity and psychopathology. Optimization of epigenetic research activity necessitates a discussion surrounding the methodologies used for DNA methylation analysis, selection of tissue sources, and timing of psychological and biological assessments. Recent studies related to early-life adversity and methylation, including both candidate gene and epigenome-wide association studies, have drawn from the variety of available techniques to generate interesting data in the field. Further discussion is warranted to address the limitations inherent to this field of research, along with future directions for epigenetic studies of adversity-related psychopathology. Highlights of the article We identified issues regarding sample characteristics in epigenetic studies of early life adversity. We compared methods and technologies used for candidate gene analysis and whole epigenome studies. We discussed future perspectives, including combining multiple forms of large-scale data and newer technologies.

[1]  F. Holsboer,et al.  Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation , 2016, Biological Psychiatry.

[2]  Tom R. Gaunt,et al.  Systematic identification of genetic influences on methylation across the human life course , 2016, Genome Biology.

[3]  Gustavo Turecki,et al.  Suicide and suicidal behaviour , 2016, The Lancet.

[4]  Jingyu Liu,et al.  Correspondence of DNA Methylation Between Blood and Brain Tissue and Its Application to Schizophrenia Research. , 2016, Schizophrenia bulletin.

[5]  S. Guillaume,et al.  Borderline personality disorder and childhood maltreatment: A genome-wide methylation analysis , 2016, European Psychiatry.

[6]  J. Mill,et al.  Variation in 5-hydroxymethylcytosine across human cortex and cerebellum , 2016, Genome Biology.

[7]  Z. Kaminsky,et al.  Role of epigenetic factors in the development of mental illness throughout life , 2016, Neuroscience Research.

[8]  M. Meaney,et al.  Effects of the Social Environment and Stress on Glucocorticoid Receptor Gene Methylation: A Systematic Review , 2016, Biological Psychiatry.

[9]  B. Baune,et al.  Epigenetic alterations following early postnatal stress: a review on novel aetiological mechanisms of common psychiatric disorders , 2015, Clinical Epigenetics.

[10]  Kathryn K. Ridout,et al.  Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5) , 2015, Development and Psychopathology.

[11]  J. Mill,et al.  Interindividual methylomic variation across blood, cortex, and cerebellum: implications for epigenetic studies of neurological and neuropsychiatric phenotypes , 2015, Epigenetics.

[12]  W. McArdle,et al.  Lymphoblastoid cell lines reveal associations of adult DNA methylation with childhood and current adversity that are distinct from whole blood associations. , 2015, International journal of epidemiology.

[13]  H. Frieling,et al.  DNA methylation results depend on DNA integrity—role of post mortem interval , 2015, Front. Genet..

[14]  Matthew D. Schultz,et al.  Human Body Epigenome Maps Reveal Noncanonical DNA Methylation Variation , 2015, Nature.

[15]  J. Hudziak,et al.  Adverse Life Events and Allele-Specific Methylation of the Serotonin Transporter Gene (SLC6A4) in Adolescents: The TRAILS Study , 2015, Psychosomatic medicine.

[16]  G. Turecki,et al.  Childhood maltreatment and stress-related psychopathology: the epigenetic memory hypothesis. , 2015, Current pharmaceutical design.

[17]  B. Birmaher,et al.  Familial pathways to early-onset suicide attempt: a 5.6-year prospective study. , 2015, JAMA psychiatry.

[18]  Michael Q. Zhang,et al.  Integrative analysis of 111 reference human epigenomes , 2015, Nature.

[19]  P. Courtet,et al.  Borderline personality disorder and childhood maltreatment: a genome‐wide methylation analysis , 2015, Genes, brain, and behavior.

[20]  D. Pfaff,et al.  Sexually dimorphic responses to early adversity: Implications for affective problems and autism spectrum disorder , 2014, Psychoneuroendocrinology.

[21]  A. Jackowski,et al.  Early life adversity, genomic plasticity, and psychopathology. , 2014, The lancet. Psychiatry.

[22]  G. Turecki.  The molecular bases of the suicidal brain , 2014, Nature Reviews Neuroscience.

[23]  H. Steiger,et al.  Methylation of BDNF in women with bulimic eating syndromes: Associations with childhood abuse and borderline personality disorder , 2014, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[24]  K. Räikkönen,et al.  Epigenomic profiling of men exposed to early-life stress reveals DNA methylation differences in association with current mental state , 2014, Translational Psychiatry.

[25]  Nongluk Plongthongkum,et al.  Advances in the profiling of DNA modifications: cytosine methylation and beyond , 2014, Nature Reviews Genetics.

[26]  C. Kirschbaum,et al.  Effects of genetic and early environmental risk factors for depression on serotonin transporter expression and methylation profiles , 2014, Translational Psychiatry.

[27]  M. Szyf,et al.  Hydroxymethylation and DNA methylation profiles in the prefrontal cortex of the non-human primate rhesus macaque and the impact of maternal deprivation on hydroxymethylation , 2014, Neuroscience.

[28]  M. Pembrey,et al.  Childhood abuse is associated with methylation of multiple loci in adult DNA , 2014, BMC Medical Genomics.

[29]  Guoping Fan,et al.  Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain , 2013, Nature Neuroscience.

[30]  Stephen J Glatt,et al.  On the outside, looking in: A review and evaluation of the comparability of blood and brain “‐omes” , 2013, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[31]  E. Koonin,et al.  Differences in DNA methylation between human neuronal and glial cells are concentrated in enhancers and non-CpG sites , 2013, Nucleic acids research.

[32]  Matthew D. Schultz,et al.  Global Epigenomic Reconfiguration During Mammalian Brain Development , 2013, Science.

[33]  A. Gnirke,et al.  Charting a dynamic DNA methylation landscape of the human genome , 2013, Nature.

[34]  J. Mill,et al.  Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities. , 2013, The international journal of neuropsychopharmacology.

[35]  F. Champagne,et al.  Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes , 2013, Front. Psychiatry.

[36]  E. J. van den Oord,et al.  Testing two models describing how methylome-wide studies in blood are informative for psychiatric conditions. , 2013, Epigenomics.

[37]  Bastiaan T. Heijmans,et al.  From promises to practical strategies in epigenetic epidemiology , 2013, Nature Reviews Genetics.

[38]  Hongyu Zhao,et al.  Profiling of Childhood Adversity-Associated DNA Methylation Changes in Alcoholic Patients and Healthy Controls , 2013, PloS one.

[39]  B. Birmaher,et al.  Early childhood sexual abuse increases suicidal intent , 2013, World psychiatry : official journal of the World Psychiatric Association.

[40]  C. Nemeroff,et al.  Decreased cortical representation of genital somatosensory field after childhood sexual abuse. , 2013, The American journal of psychiatry.

[41]  Martin J. Aryee,et al.  A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression , 2013, Epigenetics.

[42]  A. Malafosse,et al.  Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene , 2013, Translational Psychiatry.

[43]  N. Heintz,et al.  MeCP2 binds to 5hmc enriched within active genes and accessible chromatin in the nervous system , 2012, Epigenetics & Chromatin.

[44]  E. Baca-García,et al.  Suicidal phenotypes associated with family history of suicidal behavior and early traumatic experiences. , 2012, Journal of affective disorders.

[45]  B. Bradley,et al.  Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions , 2012, Nature Neuroscience.

[46]  F. Champagne,et al.  Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways , 2012, Development and Psychopathology.

[47]  Patrick O. McGowan,et al.  Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus , 2012, Proceedings of the National Academy of Sciences.

[48]  Michael J Meaney,et al.  Genome-wide epigenetic regulation by early-life trauma. , 2012, Archives of general psychiatry.

[49]  M. Szyf,et al.  Differential Glucocorticoid Receptor Exon 1B, 1C, and 1H Expression and Methylation in Suicide Completers with a History of Childhood Abuse , 2012, Biological Psychiatry.

[50]  M. Szyf,et al.  Peripheral SLC6A4 DNA Methylation Is Associated with In Vivo Measures of Human Brain Serotonin Synthesis and Childhood Physical Aggression , 2012, PloS one.

[51]  R. Dobson,et al.  Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood , 2012, Genome Biology.

[52]  Devin C. Koestler,et al.  DNA methylation arrays as surrogate measures of cell mixture distribution , 2012, BMC Bioinformatics.

[53]  B. Wanner,et al.  Childhood trajectories of anxiousness and disruptiveness explain the association between early-life adversity and attempted suicide , 2012, Psychological Medicine.

[54]  Elisabeth B. Binder,et al.  Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene–environment interactions, and epigenetics , 2012, Experimental Neurology.

[55]  P. Courtet,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 , 2011, Translational Psychiatry.

[56]  C. Nemeroff,et al.  Neurobiological and psychiatric consequences of child abuse and neglect. , 2010, Developmental psychobiology.

[57]  J. John Mann,et al.  Genome-Wide Divergence of DNA Methylation Marks in Cerebral and Cerebellar Cortices , 2010, PloS one.

[58]  Robert A Philibert,et al.  Methylation at SLC6A4 is linked to family history of child abuse: An examination of the Iowa Adoptee sample , 2010, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[59]  R. Kessler,et al.  Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. , 2010, Archives of general psychiatry.

[60]  R. Kessler,et al.  Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication I: associations with first onset of DSM-IV disorders. , 2010, Archives of general psychiatry.

[61]  Gustavo Turecki,et al.  Familial aggregation of suicide explained by cluster B traits: a three-group family study of suicide controlling for major depressive disorder. , 2009, The American journal of psychiatry.

[62]  Gustavo Turecki,et al.  Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse , 2009, Nature Neuroscience.

[63]  D. Fergusson,et al.  Burden and consequences of child maltreatment in high-income countries , 2008, The Lancet.

[64]  Vikram Patel,et al.  Depression, chronic diseases, and decrements in health: results from the World Health Surveys , 2007, The Lancet.

[65]  R. Tremblay,et al.  Natural history of suicidal behaviors in a population-based sample of young adults , 2007, Psychological Medicine.

[66]  Eric J. Nestler,et al.  Epigenetic regulation in psychiatric disorders , 2007, Nature Reviews Neuroscience.

[67]  Avshalom Caspi,et al.  Gene–environment interactions in psychiatry: joining forces with neuroscience , 2006, Nature Reviews Neuroscience.

[68]  A. Bird,et al.  Genomic DNA methylation: the mark and its mediators. , 2006, Trends in biochemical sciences.

[69]  W. Lam,et al.  Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells , 2005, Nature Genetics.

[70]  I. Weaver,et al.  Epigenetic programming by maternal behavior , 2004, Nature Neuroscience.

[71]  Jochen Hardt,et al.  Validity of adult retrospective reports of adverse childhood experiences: review of the evidence. , 2004, Journal of child psychology and psychiatry, and allied disciplines.

[72]  D. Fergusson,et al.  Risk factors and life processes associated with the onset of suicidal behaviour during adolescence and early adulthood , 2000, Psychological Medicine.

[73]  A. Bifulco,et al.  Childhood Experience of Care and Abuse (CECA): a retrospective interview measure. , 1994, Journal of child psychology and psychiatry, and allied disciplines.

[74]  J Foote,et al.  Initial reliability and validity of a new retrospective measure of child abuse and neglect. , 1994, The American journal of psychiatry.

[75]  J. Minárovits,et al.  Epigenetic Regulation. , 2016, Advances in experimental medicine and biology.