Genes and Environment: Multiple Pathways to Psychopathology

Abstract

In this issue of Biological Psychiatry, the work by van IJzendoorn et al. ( 1 van IJzendoorn M.H. Caspers K. Bakermans-Kranenburg M.J. Steven R.H. Beach R. Philibert Methylation matters: interaction between methylation density and serotonin transporter genotype predicts unresolved loss or trauma. Biol Psychiatry. 2010; 68: 405-407 Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar ) describes how the report of a previous abusive event in children adopted shortly after birth can result in unresolved grief or loss, depending on the serotonin-transporter (5HTT) gene promoter region polymorphism and DNA methylation levels of an associated CpG island. This study attempts to determine whether genetic and epigenetic factors can contribute to increased vulnerability to loss and attachment-related trauma. Clinical studies have found that reported childhood adversity such as physical or sexual abuse or deprivation are risk factors for psychopathology in later childhood and adulthood. Examples of such psychopathology include mood disorders, anxiety disorders, and suicide. At the same time there is evidence that these disorders are heritable, although the identities of the genes involved in the etiology of such psychopathology have remained elusive. Not all those exposed to adversity during childhood manifest psychopathology later in life, indicating the existence of a diathesis in some but not all individuals. Studies have shown that the risk of psychopathology in those with a reported history of childhood adversity is affected by genotype ( 2 Caspi A. Sugden K. Moffitt T.E. Taylor A. Craig I.W. Harrington H. et al. Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science. 2003; 301: 386-389 Crossref PubMed Scopus (6152) Google Scholar ). Such gene–environment interactions have been observed clinically for a number of genes, such as the 5HTT, monoamine oxidase A, catechol O-methyl transferase, and the glucocorticoid receptor. Understanding how genes and the environment interact in increasing the risk of psychopathology requires studying the influence of the environment on gene expression. Epigenetics might be a mediating factor, in that the environment might alter the epigenome, and these alterations in epigenetic marks might then influence gene expression and dynamics. Methylation Matters: Interaction Between Methylation Density and Serotonin Transporter Genotype Predicts Unresolved Loss or TraumaBiological PsychiatryVol. 68Issue 5PreviewDo genetic or epigenetic factors play a role in making some individuals more vulnerable than others to loss of attachment figures or other traumatic experiences? Full-Text PDF