Behavioral Neurobiology of PTSD

Ulrike Schmidt, Eric Vermetten, Schmidt, Ulrike, Vermetten, Eric

Three and a half decades of research on posttraumatic stress disorder (PTSD) has produced substantial knowledge on the pathobiology of this frequent and debilitating disease. However, despite all research efforts, so far no drug that has specifically targeted PTSD core symptoms progressed to clinical use. Instead, although not overly efficient, serotonin re-uptake inhibitors continue to be considered the gold standard of PTSD pharmacotherapy. The psychotherapeutic treatment and symptom-oriented drug therapy options available for PTSD treatment today show some efficacy, although not in all PTSD patients, in particular not in a substantial percent of those suffering from the detrimental sequelae of repeated childhood trauma or in veterans with combat related PTSD. PTSD has this in common with other psychiatric disorders - in particular effective treatment for incapacitating conditions such as resistant major depression, chronic schizophrenia, and frequently relapsing obsessive-compulsive disorder as well as dementia has not yet been developed through modern neuropsychiatric research.In response to this conundrum, the National Institute of Mental Health launched the Research Domain Criteria (RDoC) framework which aims to leave diagnosis-oriented psychiatric research behind and to move on to the use of research domains overarching the traditional diagnosis systems. To the best of our knowledge, the paper at hand is the first that has systematically assessed the utility of the RDoC system for PTSD research. Here, we review core findings in neurobiological PTSD research and match them to the RDoC research domains and units of analysis. Our synthesis reveals that several core findings in PTSD such as amygdala overactivity have been linked to all RDoC domains without further specification of their distinct role in the pathophysiological pathways associated with these domains. This circumstance indicates that the elucidation of the cellular and molecular processes ultimately decisive for regulation of psychic processes and for the expression of psychopathological symptoms is still grossly incomplete. All in all, we find the RDoC research domains to be useful but not sufficient for PTSD research. Hence, we suggest adding two novel domains, namely stress and emotional regulation and maintenance of consciousness. As both of these domains play a role in various if not in all psychiatric diseases, we judge them to be useful not only for PTSD research but also for psychiatric research in general.