Early-Life Experience, Epigenetics, and the Developing Brain

REVIEW Neuropsychopharmacology REVIEWS (2015) 40, 141–153 & 2015 American College of Neuropsychopharmacology. All rights reserved 0893-133X/15 ............................................................................................................................................................... www.neuropsychopharmacologyreviews.org Early-Life Experience, Epigenetics, and the Developing Brain Marija Kundakovic1 and Frances A Champagne*,1 1 Department of Psychology, Columbia University, New York, NY, USA Development is a dynamic process that involves interplay between genes and the environment. In mammals, the quality of the postnatal environment is shaped by parent–offspring interactions that promote growth and survival and can lead to divergent developmental trajectories with implications for later-life neurobiological and behavioral characteristics. Emerging evidence suggests that epigenetic factors (ie, DNA methylation, posttranslational histone modifications, and small noncoding RNAs) may have a critical role in these parental care effects. Although this evidence is drawn primarily from rodent studies, there is increasing support for these effects in humans. Through these molecular mechanisms, variation in risk of psychopathology may emerge, particularly as a consequence of early-life neglect and abuse. Here we will highlight evidence of dynamic epigenetic changes in the developing brain in response to variation in the quality of postnatal parent–offspring interactions. The recruitment of epigenetic pathways for the biological embedding of early-life experience may also have transgenerational consequences and we will describe and contrast two routes through which this transmission can occur: experience dependent vs germline inheritance. Finally, we will speculate regarding the future directions of epigenetic research and how it can help us gain a better understanding of the developmental origins of psychiatric dysfunction. Neuropsychopharmacology Reviews (2015) 40, 141–153; doi:10.1038/npp.2014.140; published online 30 July 2014 INTRODUCTION Development typically occurs within a social context comprising parents, siblings, and other caregivers or group members. This context provides for the developmental needs of offspring, such as feeding, sensory stimulation, and emotional warmth, but may also serve as a critical cue to the type of environment in which immediate and later development will take place. For example, although basic needs may be met through the efforts of a single caregiver, the absence of other individuals (eg, friends and relatives) may indicate a lack of social support or financial constraint, which may typify the environment to be experienced over the lifespan. Given the potential value of these environmental signals in predicting both the current and future socioeconomic context, it is perhaps not surprising that the quality of the early-life environment can have a sustained impact on our biology, leading to divergent developmental trajectories. In particular, the quality of parent–offspring interactions can shape the developing brain with long-term implications for brain function and *Correspondence: Dr FA Champagne, Department of Psychology, Columbia University, 406 Schermerhorn Hall, 1190 Amsterdam Avenue, New York, NY 10027, USA, Tel: +1 212 854 2589, Fax: +1 212 854 3609, E-mail: Received 14 April 2014; revised 3 June 2014; accepted 5 June 2014; accepted article preview online 11 June 2014 behavior. A critical question raised by decades of research into the developmental effects of parenting is regarding mechanism: how does the experience of variation in parental care lead to lifelong changes in neurobiology and behavior? The search for mechanism(s) underlying the impact of parents on offspring has progressed rapidly in the past decade in light of modern advances in molecular biology and brain imaging that point toward pathways, which may be common to many early-life experiences (ie, exposure to toxins, nutritional variation, and stress). In particular, it is evident that the quality of parent–offspring interactions induce epigenetic changes in the developing brain that account for variation in response to stress, cognition, sociality, and reproductive behavior. Epigenetics is an evolving field of study that focuses not on the sequence of DNA within our genomes but rather on regulation of the ‘activity’ of genes. These epigenetic mechanisms may help us to better understand the biological impact of a broad range of environmental experiences, which include the quality of parental care. Moreover, it is clear that the impact of early-life experiences may influence subsequent generations of offspring. In this review, we will highlight evidence for the neurobiological and behavioral impact of parent– offspring interactions occurring during the postnatal period, the epigenetic mechanisms through which these effects may be achieved, and explore the transgenerational consequences of parental care and early-life adversity. .............................................................................................................................................. Neuropsychopharmacology REVIEWS 141 Epigenetic effects of early-life experience M Kundakovic and FA Champagne REVIEW ............................................................................................................................................................... 142 ENDURING IMPACT OF PARENTAL CARE .............................................................................................................................................. Neuropsychopharmacology REVIEWS Standardized value 0 High maternal care –0.5 tn eg a af tive fe ct In fa n Po si ti at ve te jo nt int io n Fr o as nta ym l E m EG et ry In fa n re t fe sp ar on fu se l Childhood outcomes: Age 2–3 years 1 0.5 Low maternal care 0 High maternal care –0.5 Ag g pe res er si pl ve ay hi So bi cia tio l n -1 in Research on the developmental impact of human parental behaviors has focused on the quality of the attachment, sensitivity to infant cues, parental bonding, and disturbances to the parent–child relationship through parental absence (ie, institutional rearing), neglect, and abusive caregiving. Variations in the attachment relationship (typically examined between mother and infant) are associated with either resilience to psychological distress (eg, secure attachment) or increased incidence of psychopathology (eg, disorganized attachment) (Sroufe, 2005). Disorganized attachment is predictive of increased rates of personality disorder, dissociation, self-harm, and increases in salivary cortisol during exposure to stressors, suggesting heightened reactivity of the hypothalamic–pituitary–adrenal (HPA) response to stress (Bernard and Dozier, 2010; Carlson, 1998; Carlson et al, 2009; van Ijzendoorn et al, 1999). Among infants whose mothers are characterized as exhibiting a (...truncated)