PTSD, Endophenotypes, the RDoC, and the DSM-5

The search for endophenotypes that stand between genetics and disease has been applied to the diagnostic entity of Posttraumatic Stress Disorder (PTSD). Advances are being made in understanding the pathway to disorder in PTSD in terms of brain regions, neuronal networks, stress-related systems (e.g., the hypothalamic-pituitary-adrenal (HPA) axis), and their underlying genetic and neurogenetic bases. The latter are affected by gene-environmental interactions and epigenetic effects, and the environment and context reciprocally interrelate with them, as well. Therefore, a primary focus on (neuro)pathophysiological intermediates in the disease pathway, as appears emphasized in the research domain criteria (RDoC) approach to etiology of psychiatric disorder, and to which the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) subscribes, might detract from a more inclusive biopsychosocial approach that would be more applicable in the case of PTSD. The paper undertakes a comprehensive review of the recent literature in the areas of endophenotypes, neurogenetics, epigenetics, neural networks, HPA axis, neuronal networks, pathways, the PTSD five-factor model, allostasis, and the RDoC criteria for psychiatric diagnosis, and then returns to the topic of endophenotypes. Neuronal networks constitute one integrating area that could help in arriving at an appropriate model of PTSD endophenotype. Pathway analysis provides a rich field for discerning individual differences in PTSD development, more so than the static approach of using DSM-5 symptom criteria. A model of endophenotypes is presented, which considers these factors in relation to PTSD. The paper concludes with implications for the DSM-5, for practice and for court, especially that it would be premature to seek individual biomarkers of PTSD given the current state of knowledge, even if it is burgeoning. © 2014 Springer Science+Business Media New York.