Early life programming and neurodevelopmental disorders.
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 Early theories about psychic conflict and toxic parenting have been replaced by more recent formulations of complex interactions of genes and environment.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.
Bale
Tracy L
TL
Department of Animal Biology, University of Pennsylvania, Philadelphia, Pennsylvania.
Baram
Tallie Z
TZ
Brown
Alan S
AS
Goldstein
Jill M
JM
Insel
Thomas R
TR
McCarthy
Margaret M
MM
Nemeroff
Charles B
CB
Reyes
Teresa M
TM
Simerly
Richard B
RB
Susser
Ezra S
ES
Nestler
Eric J
EJ
D000818:Animals; D001921:Brain / Q000254:growth & development / Q000503:physiopathology; D004195:Disease Models, Animal; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D047109:Fetal Development / Q000235:genetics* / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006801:Humans; D018811:Maternal Exposure; D001523:Mental Disorders / Q000235:genetics* / Q000503:physiopathology; D012737:Sex Factors