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Human epidemiological studies and studies of animal models provide many examples by which early life experiences influence health in a long-term manner, a concept known as biological embedding. Such experiences can have profound impacts during periods of high plasticity in prenatal and early postnatal life. Epigenetic mechanisms influence gene function in the absence of changes in gene sequence. In contrast to the relative stability of gene sequences, epigenetic mechanisms appear, at least to some extent, responsive to environmental signals. To date, a few examples appear to clearly link early social experiences to epigenetic changes in pathways relevant for mental health in adulthood. Our recent work using high-throughput epigenomic techniques points to large-scale changes in gene pathways in addition to candidate genes involved in the response to psychosocial stress and neuroplasticity. Elucidation of which pathways are epigenetically labile under what conditions will enable a more complete understanding of how the epigenome can mediate environmental interactions with the genome that are relevant for mental health. In this mini-review, we provide examples of nascent research into the influence of early life experience on mental health outcomes, discuss evidence of epigenetic mechanisms that may underlie these effects, and describe challenges for research in this area. Key words: epigenetics, DNA methylation, early life adversity, psychiatric disorders, animal models. Des etudes epidemiologiques realisees chez l'humain et des etudes portant sur des modeles animaux fournissent plusieurs exemples dans lesquels des experiences vecues tot dans la vie influencent la sante a long terme, un concept connu sous l'appellation de<>. De telles experiences peuvent avoir de profonds impacts durant les periodes de haute plasticite lors de la vie prenatale et tot apres la naissance. Les mecanismes epigenetiques influencent la fonction des genes en absence de changements dans leur sequence. A la difference de la relative stabilite des sequences geniques, les mecanismes epigenetiques semblent, du moins dans une certaine mesure, repondre aux signaux environnementaux. Jusqu'a present, quelques exemples semblent lier clairement des experiences sociales vecues precocement a des changements epigenetiques dans des sentiers pertinents a la sante mentale a l'age adulte. Nos recents travaux realises a l'aide de techniques epigenomiques a haut debit indiquent la presence de changements a grande echelle dans des sentiers geniques en plus des genes candidats impliques dans la reponse au stress psychosocial et la neuroplasticite. De savoir quels sont les sentiers labiles au plan epigenetique et sous quelles conditions ils le sont nous permettra de mieux comprendre comment l'epigenome peut intervenir dans les interactions de l'environnement avec le genome, qui sont pertinentes a la sante mentale. Dans cette mini-revue, nous donnons des exemples de la recherche emergente portant sur les experiences vecues tot dans la vie et leurs consequences sur la sante mentale, nous discutons des donnees qui revelent que des mecanismes epigenetiques peuvent sous-tendre ces effets, et nous decrivons les defis que pose la recherche dans ce domaine. [Traduit par la Redaction] Mots-cles: epigenetique, methylation d'ADN, epreuves vecues dans l'enfance, maladies psychiatriques, modeles animaux., Biological embedding and mental health The concept of biological embedding has gained substantial traction as a framework for understanding the roots of complex multifactorial phenomena in health and disease (McGowan [...]

Effects of stresses associated with extremely preterm birth may be biologically "recorded" in the genomes of individuals born preterm via changes in DNA methylation (DNAm) patterns. Genome-wide DNAm profiles were examined in buccal epithelial cells from 45 adults born at extremely low birth weight (ELBW; ≤1000 g) in the oldest known cohort of prospectively followed ELBW survivors (Mage = 32.35 years, 17 male), and 47 normal birth weight (NBW; ≥2500 g) control adults (Mage = 32.43 years, 20 male). Sex differences in DNAm profiles were found in both birth weight groups, but they were greatly enhanced in the ELBW group (77,895 loci) versus the NBW group (3,424 loci), suggesting synergistic effects of extreme prenatal adversity and sex on adult DNAm profiles. In men, DNAm profiles differed by birth weight group at 1,354 loci on 694 unique genes. Only two loci on two genes distinguished between ELBW and NBW women. Gene ontology (GO) and network analyses indicated that loci differentiating between ELBW and NBW men were abundant in genes within biological pathways related to neuronal development, synaptic transportation, metabolic regulation, and cellular regulation. Findings suggest increased sensitivity of males to long-term epigenetic effects of extremely preterm birth. Group differences are discussed in relation to particular gene functions. [ABSTRACT FROM AUTHOR]

Long‐term sequelae of extremely low birth weight (ELBW; ≤1000 g) may contribute to accelerated biological aging. This hypothesis was examined by analyzing a range of risk factors with a molecular age marker in adults born at ELBW or normal birth weight (NBW; ≥2500 g). DNAm age—the weighted average of DNA methylation at 353 cytosine–phosphate–guanine (CpG) sites from across the genome—was derived from a sample of 45 ELBW (Mage = 32.35 years) and 47 NBW control (Mage = 32.44 years) adults, using the Illumina 850k BeadChip Array. At two assessments undertaken 9 years apart (at 23 and 32 years), cumulative risks were summed from six domains with potential to affect physiological and psychological health: resting respiratory sinus arrhythmia, blood pressure, basal cortisol, grip strength, body mass index, and self‐esteem. At age 32 years, cumulative risks were differentially associated with epigenetic age in ELBW survivors (interaction, p < 0.01). For each additional risk factor they possessed, ELBW survivors (B = 1.43) were biologically 2.16 years older than NBW adults (B = –0.73), by the fourth decade of life. Developmental change, epigenetic maintenance, and intervention targets are discussed. [ABSTRACT FROM AUTHOR]