Work

Genes learn from stress: How infantile trauma programs us for depression

Year: 2010

Type: article

Abstract: Early-life stress induces persistent memory traces on our genes and programs the life-long risk for depression. Epigenetic marking of the arginine vasopressin (AVP) gene by early-life stress in mice underpins sustained expression and increased hypothalamic-pituitary-adrenal axis activity, triggering endocrine and behavioral alterations that are frequent features in depression. This epigenetic memory evolves in two steps coordinated by the epigenetic reader and writer MeCP2. While early derepression of AVP is driven by neuronal activity causing Ca2+/calmodulin kinase-dependent phosphorylation and dissociation of MeCP2, subsequent hypomethylation at the AVP enhancer gradually develops to sustain derepression. In a vicious circle MeCP2 occupancy uncouples from the initial stimulus and leads to the hard-coding of early-life experience at the level of DNA methylation. The sequential order of these events demarcates the transition from a preliminary to a persistent, possibly irreversible, epigenetic memory and thus defines a critical time window for the timely therapy of severe trauma.

Source: Epigenetics

DOI: 10.4161/epi.5.3.11375

Authors: Chris Murgatroyd, Yonghe Wu, Yvonne Bockmühl, Dietmar Spengler

Institutions: Max Planck Society, Max Planck Institute of Psychiatry

Language: English

Topic: Epigenetics and DNA Methylation

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funder: European Commission