Early Life Programming and Neurodevelopmental Disorders

Abstract

For more than a century, clinical investigators have focused on early life as a source of adult psychopathology. Early theories about psychic conflict and toxic parenting have been replaced by more recent formulations of complex interactions of genes and environment. Although the hypothesized mechanisms have evolved, a central notion remains: early life is a period of unique sensitivity during which experience confers enduring effects. The mechanisms for these effects remain almost as much a mystery today as they were a century ago. Recent studies suggest that maternal diet can program offspring growth and metabolic pathways, altering lifelong susceptibility to diabetes and obesity. If maternal psychosocial experience has similar programming effects on the developing offspring, one might expect a comparable contribution to neurodevelopmental disorders, including affective disorders, schizophrenia, autism, and eating disorders. Due to their early onset, prevalence, and chronicity, some of these disorders, such as depression and schizophrenia, are among the highest causes of disability worldwide according to the World Health Organization 2002 report. Consideration of the early life programming and transcriptional regulation in adult exposures supports a critical need to understand epigenetic mechanisms as a critical determinant in disease predisposition. Incorporating the latest insight gained from clinical and epidemiological studies with potential epigenetic mechanisms from basic research, the following review summarizes findings from a workshop on Early Life Programming and Neurodevelopmental Disorders held at the University of Pennsylvania in 2009.

Perinatal and juvenile social environments interact to shape cognitive behaviour and neural phenotype in prairie voles

“…Taken together, these results demonstrate that social environments experienced during pre-weaning and postweaning influence neural development in a region-specific manner, and can interactively shape neural and behavioural phenotype. by classic and recent studies has shown that disruption of mother -infant interactions has consequences for the physiology and social behaviour of adult offspring [43][44][45][46]. Despite the significant advances that studies such as these have made, the majority of research performed has focused on maternal care and has overlooked the contribution of fathers on offspring development.…”

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

“…18 BDNF expression is sensitive to early-life environment [19][20][21] and specifically hypoxic-stressors, 22,23 which, in turn, are critical factors involved in the pathophysiology of schizophrenia. [24][25][26][27] The failure to find association between BDNF and schizophrenia in large-scale case control studies may conceivably reflect a complex interaction of genotype and environmental experience that alters methylation status.…”

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks

“…Although some of these processes are complete at birth, the early postnatal brain is far from maturity and continues to undergo significant developmental processes; these processes include axonal and dendritic growth, synaptic stabilization, and synaptic pruning (Bale et al, 2010;Regev and Baram, 2014;Hoeijmakers et al, 2015). The perinatal period therefore represents a critical stage of development, rendering the brain particularly vulnerable to organizing (and disorganizing) environmental influences.…”