The Need to Take a Staging Approach to the Biological Mechanisms of PTSD and its Treatment

Alexander Cowell McFarlane, Eleanor Lawrence-Wood, Miranda Van Hooff, Gin S. Malhi, Rachel Yehuda

Despite the substantial body of neurobiological research, no specific drug target has been developed to treat PTSD and there are substantial limitations with the available interventions. We propose that advances are likely to depend on the development of better classification of the heterogeneity of PTSD using a staging approach of disease. A primary rationale for staging is to highlight the probability that distinct therapeutic approaches need to be utilised according to the degree of biological progression of the disorder. Prospective studies, particularly of military populations, provide substantial evidence about the emerging biological abnormalities that precede the full-blown disorder. These need to be targeted with tailored interventions to prevent disease progression. Equally, the neurobiology of chronic unremitting PTSD needs to be differentiated from the acute disorder which emerges across a spectrum of severity, and this range of presentations correspondingly needs to be addressed with differing therapeutic strategies. The staging approach also needs to take account of the range of somatic pathological outcomes that are being identified as a consequence of traumatic stress exposure. PTSD should be conceptualised as a systemic disorder underpinned a range of biological dysregulation, including metabolic and altered immune function, reflected in the increased rates of cardiovascular and autoimmune disease. The effectiveness of novel treatments needs to be judged across their effectiveness in addressing the spectrum of trauma-related pathology.