Disease markers: molecular biology of PTSD.

There have been significant advances in understanding the phenomenology and biology of PTSD in the more than thirty years since the disorder first appeared in the DSM-III. However, as we stand in the crossroads towards DSM-V, it is clear that scientific efforts in the examination of PTSD have yielded more questions than they have answered. PTSD was initially described as a condition in which “the essential feature is the development of characteristic symptoms following a psychologically traumatic event that is generally outside the range of usual human experience” (APA, 1980). It was not only implied, but made explicit in the DSM-III, that the symptoms result from the trauma exposure. Thus, the one question that investigators did not feel they had to attend to in the early years of research on this disorder was what causes PTSD. Rather, initial investigations focused on demonstrating that persons who experience extreme trauma showed alterations in biological systems that have also been implicated in chronic stress and/or identified as correlates of fear. A variety of converging findings have now provided a scientific mandate to answer the question of what causes PTSD. First and foremost are results from epidemiologic studies demonstrating that only a proportion of trauma exposed persons develop PTSD. These studies have led to the conclusion that trauma exposure alone is not a sufficient causal agent. Furthermore, it has become clear that the findings related to stress or fear neurobiology may not be fully or completely applicable to the PTSD phenotype. It is true that the two major stress-responsive biological systems – the hypothalamic pituitary adrenal (HPA) axis and sympathetic nervous system (SNS) – seem to be dysregulated in PTSD. However, it has not been possible to conclude from extant findings that the PTSD neurobiology is analogous to the classical neurobiology of chronic stress or fear. While stress neurobiology arguably explains the emergence of some symptoms in the acute aftermath of trauma, it has not been able to explain either the persistence of those symptoms in the subset of trauma survivors who do not recover, or why such persons do not undergo what is arguably the defining hallmark of the stress response – the recalibration of biological systems towards homeostasis. Given these existing questions, the next generation of biological studies in PTSD must evaluate a broader range of biological mechanisms, and this examination must include molecular biology. It is for this reason that we have compiled a volume that puts together a series of conceptually related papers on the emerging molecular biology of PTSD. In that this is a new field, a volume that summarizes various methodological and theoretical approaches may have value in creating a scaffolding for future studies. Molecular biology is an approach that focuses on integrating information about the functioning of different cellular components. This includes how information travels from DNA to RNA, from RNA to protein synthesis, and ultimately from protein synthesis to function and behavior. Molecular biology is not only interested in the regulation of transcription and translation, but also in other processes of gene regulation including epigenetic regulation or genomic imprinting. The latter mechanisms are particularly interesting to examine in PTSD because they may reflect enduring consequences of environmental perturbations. In turn, epigenetic alterations can influence other molecular processes such as transcriptional and post-transcriptional regulation (e.g., sequestration, alternative splicing, trans-