Epigenetic mechanisms in the development of behavior: advances, challenges, and future promises of a new field

Abstract

In the past decade, there have been exciting advances in the field of behavioral epigenetics that have provided new insights into a biological basis of neural and behavioral effects of gene-environment interactions. It is now understood that changes in the activity of genes established through epigenetic alterations occur as a consequence of exposure to environmental adversity, social stress, and traumatic experiences. DNA methylation in particular has thus emerged as a leading candidate biological pathway linking gene-environment interactions to long-term and even multigenerational trajectories in behavioral development, including the vulnerability and resilience to psychopathology. This paper discusses what we have learned from research using animal models and from studies in which the translation of these findings has been made to humans. Studies concerning the significance of DNA methylation alterations in outcomes associated with stress exposure later in life and dysfunction in the form of neuropsychiatric disorders are highlighted, and several avenues of future research are suggested that promise to advance our understanding of epigenetics both as a mechanism by which the environment can contribute to the development of psychiatric disorders and as an avenue for more effective intervention and treatment strategies.

Figures

Figure 1

DNA compaction and methylation. (A) DNA in the nucleus is wrapped around histone proteins, forming what is referred to as chromatin. This provides a highly ordered packaging state of DNA to serve as a building block of chromosomes. (B) DNA methylation occurs at cytosine residues of cytosine-guanine (CG) dinucleotides that are often clustered within gene regulatory regions. DNA methylation is an epigenetic mechanism typically associated with gene suppression, as methyl groups can either interfere with the binding of transcription factors necessary to promote gene transcription and/or recruit repressor proteins that promote a compact chromatin state not permissive to gene transcription. There are reports however of DNA methylation being associated with active gene transcription (Chahrour et al., 2008; Uchida et al., 2011).

Figure 2

Summary of psychological and social-contextual factors known to produce DNA methylation alterations. Top panel- Experiences known to produce behavioral change in both developing and adult rodents that have been linked to altered DNA methylation and gene expression profiles. These epigenetic changes occur in many brain regions with known relevance to psychopathology, several of which are depicted here. Bottom panel- Many of these animal findings have translated to similar observations in humans. A growing number of psychiatric disorders, several of which are listed here, have also been associated with DNA methylation alterations.