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

Abstract

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.

Interactive Motion-Assisted Exposure Therapy for Veterans with Treatment-Resistant Posttraumatic Stress Disorder: A Randomized Controlled Trial

“…We recommend the inclusion of a manualized specific factors component control group and long-term assessments of functioning in further randomized controlled trials. In future studies, a staging approach could help to recruit stage 4 (treatment-resistant) participants with associated biomarkers, thereby ensuring representativity of the sample [63]. Finally, cost-effectiveness studies are needed to determine whether 3MDR compares favorably with gold standard interventions taking into account treatment length and associated costs.…”

Post‐traumatic stress disorder is a systemic illness, not a mental disorder: is Cartesian dualism dead?

“…The somatic pathologies range from metabolic syndrome and related cardiovascular conditions to autoimmune diseases, including rheumatoid arthritis 2 , 4 . Such disorders have been associated with a range of quantifiable abnormalities, including inflammatory cascades, altered psychophysiological reactivity and neuroendocrine function, and shortened telomere lengths 5 …”

“…These direct somatic comorbidities highlight the fact that the pathophysiological burden of PTSD cannot be attributed to other comorbidities, but indicate the biological dysregulation inherent to this disorder, 7 a factor not systematically addressed by current treatments 8 . Many of the physiological and immune abnormalities in PTSD are also present in the subsyndromal form of the disorder, and therefore provide potential targets for early intervention 5 . One important question not explored by McLeay and colleagues is the relationship between combat exposure and physical disorder when full‐blown PTSD is absent but subsyndromal symptoms are present.…”

“…It is possible that these neurobiological dimensions may drive the relatively poor outcomes of psychological interventions. One important strategy for better understanding the sequence of the emergence of the psychological symptoms and somatic pathology in PTSD is to adopt a staging model that distinguishes the emerging matrix of the early patterns of biological dysregulation from the neurobiology of chronic, longstanding PTSD, which may reflect the secondary consequences of prolonged pathophysiological dysregulation 5 . It is only by effectively collating such evidence that we will realise that Descartes' views on dualism are completely outmoded.…”

Neuroepigenetics of Post-Traumatic Stress Disorder

“…Physiologically, this distress can be characterized in stages of systemic dysregulation 89 , including anatomical sites outside of the brain, which may be partially coordinated by maladaptive alterations of hypothalamic-pituitary adrenal (HPA) axis and sympathetic nervous system (SNS) sensitivity/responsivity, as well as neuroimmune dynamics 88,90 . Although an increasing number of human-based epigenetic studies of PTSD have adopted an epigenome-wide association study (EWAS) approach (e.g.…”