From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets

This paper touches on the complexity of post-traumatic stress disorder and the challenges associated with finding new treatment for patients with the condition. Like other anxiety disorder, PTSD is often treated with selective serotonin reuptake-inhibiting medications, and has been for decades. Psychological therapies are time-consuming and laborious, while pharmacological treatment with SSRIs suffers from lack of effect, relapse, and side effects. On top of that, both type of treatments seem to work only in a subset of patients. More effective treatment with fewer side effects is needed.

One large obstacle to pharmacological and non-pharmacological treatment of this disease is the establishment of an animal model. The large number of PTSD symptoms and the strong cognitive component in this anxiety disorder make it difficult to find a valid animal model for PTSD that meets all the criteria. There exists three animal models for PTSD currently: early life stress, inescapable foot shock (IFS), and social defeat. No model is perfect though the IFS model does provide a reproducible traumatic event, allowing researchers to manipulate the severity of the trauma for experimental reasons. While the early life stress and social defeat models may provide a benefit for the research on sensitivity to trauma, the IFS model is generally regarded as the best. However, symptoms that are not likely to be modeled in animals, such as flashbacks, intrusive memories, and nightmares, will still remain.

In an effort to reduce anxiety from PTSD via non-pharmacological means, two therapies have been identified: environmental enrichment combined with voluntary exercise and methods for re-exposure to the fear-eliciting stimulus in order to initiate extinction. Environmental enrichment enhances neurogenesis in the dentate gyrus and stimulates dendritic branching and spine forming in the hippocampus, effects also often seen after treatment with anti-depressants. By understanding the mechanisms underlying the beneficial behavioral changes of environmental enrichment, we may be able to elucidate future pharmacological treatment possibilities.

Re-exposure treatment is also an effective non-pharmacological psychological therapy option because exposure to a fearful stimulus in a safe environment can decrease the emotional reaction that this stimulus elicits in future exposures. This treatment involves an associative learning process known as ‘extinction’. MRI scans have shown that the areas involved in extinction, amygdala, hippocampus, and prefrontal cortex, are affected in PTSD patients. It is likely that re-exposure induces many other changes in gene expression. The challenge is how to identify those molecular changes that are causally related to the beneficial effects of this non-pharmacological treatment.

From the animal models discussed in the paper, the IFS model shows the most potential for patients with PTSD though it still is not perfect. Animal models help to acquire knowledge of the mechanisms underlying non-pharmacological interventions that can point out neurobiologically relevant processes leading to behavioral recovery. If we understand why the behavioral therapies are good for the brain, we may be able to identify new therapeutic targets.

Hendrikus Hendriksen, Berend Olivier, Ronald S. Oosting, From non-pharmacological treatments for post-traumatic stress disorder to novel therapeutic targets, Eur J Pharmacol. 2014;732:139-158