Epigenetics: Behavioral Influences on Gene Function, Part I: Maternal Behavior Permanently Affects Adult Behavior in Offspring.

Our ability to identify both genetic and environmental mediators of emotional-behavioral disorders in children has increased dramatically in the past decade. The human genome project, completed in 2003, fostered many other advances that have allowed us to pursue important questions about how the interaction of nature (genes) and nurture (environment) can place children at risk or protect them from psychiatric illness. During this time, the Journal published many articles demonstrating how specific candidate genes are associated with specific disorders. In addition, a few linkage genetic studies have demonstrated how multiple genetic loci across the genome contribute genetic risk to a variety of disorders. Most recently, and perhaps most important to the field of child and adolescent psychiatry, several wonderful articles have been published in our Journal and elsewhere that demonstrate the interaction between specific genes and specific environments in relation to psychiatric disorders. The majority of these articles emphasized that polymorphic genes (e.g., genes with more than one nucleotide structure due to mutations of one type or another) interact differently with different environments. The geneYenvironment interaction findings have emphasized the importance of the interaction between genetic makeup and the environment rather than focusing on the importance of one or the other. Certainly many future studies will focus on how specific environments can be risky for some and other specific environments protective for others based on the individual genotype. Such research will doubtless change the way we conceptualize, assess, and treat children with psychiatric illness. A less well-known and equally elegant line of genetic inquiry is now yielding remarkable discoveries for those of us who study developmental psychopathology. Rather than aiming to determine whether a specific mutation interacts with a specific environment, the field of epigenetics aims to determine how certain environments can turn on or turn off specific genes. This line of inquiry may be best thought of as the environmentYgene interaction approach. We now know that gene function can be altered without changing the nucleotide sequence itself. These changes are called epigenetic (from the Greek epi-, which means ‘‘on top of ’’ or ‘‘in addition to’’). The emerging field of epigenetics pursues a novel question: how does the environment interact with DNA? This column discusses the relevance of epigenetics to one area in the field of child and adolescent psychiatry, the effect of maternal care on later development and behavior. We have focused on the work of Michael Meaney, Arie Kaffman, and colleagues (see ‘‘Additional Readings’’ below), who have turned the usual line of inquiry on its head. Instead of focusing on how genes can alter behavior, they have asked how specific behaviors affect genes. When psychiatry became a rigorous field of inquiry, a debate arose as to whether genes or the environment were paramount in the development of psychopathology. The literature no longer debates this issue, as because both nature and nurture are now known to be critical modulators of normal development. How mutations (nature) can disrupt developmental processes