And then I heard him say to the nurse, ‘Scalpel please.’” Donna Penner recounts her experience on CBC’s White Coat, Black Art of when her anaesthetic wore off and she was left paralyzed. Unable to move or speak, she was forced to feel every moment of her hour and a half surgery. She was diagnosed with post-traumatic stress disorder (PTSD) two weeks after the surgery and, over the next few months, her symptoms worsened. Flashbacks were triggered by elevators, bright lights, or restrictive clothing. Night terrors disrupted her sleep, she became more anxious, and return visits to the hospital were devastating. Eight years later, the trauma was still affecting her.


A study published in CNS Neuroscience & Therapeutics comparing PTSD prevalence found that Canada had the highest of 24 countries studied, with a 9.2% lifetime risk of experiencing the disorder. While factors such as being female, experiencing maltreatment as a child, and being young at the time of the trauma are modestly predictive of PTSD development, the nature of the traumatic event along with post-trauma social support and stress levels are the most significant determinants of risk. PTSD treatment includes therapy to help the patient dismantle destructive thought patterns and learn coping strategies, and antidepressant medication to help improve mood. However, PTSD can affect people for years or decades, and contributes to the development of co-morbidities such as alcoholism and depression. New treatments may help open the door to quicker, more complete recovery.

time-heals-all-wounds-1087107_1920A group from the Division of Clinical Psychiatry Research at the University of Zurich published a study in the journal Molecular Psychiatry proposing doxycycline, a broad-spectrum antibiotic, as a candidate treatment for blocking fear memory formation. Doxycycline can inhibit the extracellular matrix metalloproteinase 9 (MMP9), an enzyme that may be integral for the cementation of threat learning. In this study, the researchers used Pavlovian-type training to teach participants, who had received either doxycycline or placebo, to associate a certain colour of screen with an electric shock. Seven days later, they put participants through a similar test, but this time the shock was replaced by a sound – was there a difference in how strongly the groups associated the colour with a threat? Participants who received doxycycline showed a 60% reduction in their startle eye blink response, indicating that they had not made as strong an association between the conditioned stimulus (coloured screen) and the threat (electric shock). During a second learning session, participants were once again put through a training session which included the electric shock. Participants who had received doxycycline showed greater surprise signals signifying that they had poorer retention of the fear memory.

While this research could inform the development of new therapeutics, use of doxycycline as a treatment for PTSD has significant drawbacks. This study doesn’t assess doxycycline’s ability to dismantle established fear memories, or the effect that altering the composition of the microbiota with prolonged antibiotic use would have on mental health. Further, disruptions to microbiotic homeostasis can lead to chronic, low-level inflammation that increases risk for some psychiatric disorders, raising the possibility that microbiotic disruption may negate any benefit from MMP9 inhibition.

Research into ways of supporting a beneficial microbiota is underway. In a study published in PNAS, Reber et al. immunized mice with heat-killed Mycobacterium vaccae and reported a stabilizing effect on the gut microbiota, increased resilience to stress-related pathologies, and increased proactive coping behaviours in mice faced with chronic psychosocial stress. M. vaccae immunization also increased mRNA expression of tph2, an enzyme at the bottleneck of the synthesis of serotonin, which promotes happiness and reduces anxiety.

Methods altering the microbiotic composition to promote resilience to stress offer a less disruptive prophylactic strategy for PTSD prevention, but the therapeutic benefits after trauma have not been investigated thoroughly. A human clinical trial using the probiotic bacteria Lactobacillus reuteri to bolster a beneficial microbiotic composition is underway. These methods could offer stress management strategies to support current therapeutic options, but will not replace effective counselling and compassionate community support.


References

  1. Awake During Surgery.White Coat Black Art (2006).
  2. Van Ameringen M et al. Post-traumatic Stress Disorder in CanadaCNS Neuroscience & Therapeutics. 14:171-181 (2008).
  3. Bach DR et al. Blocking human fear memory with the matrix metalloproteinase inhibitor doxycycline. Molecular Psychiatry. doi: 10.1038/mp.2017.65 (2017).
  4. Reber SO et al. Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice. PNAS. doi: 10.1073/pnas.1600324113 (2016).
  5. Lamb S. A shot against Post-Traumatic Stress Disorder. Scientific American (2017).
  6. Duckers MLA et al. A vulnerability paradox in the cross-national prevalence of post-traumatic stress disorder. British Journal of Psychiatry. doi: 10.1192/bjp/bp.115.176628 (2016).
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Heather MacGregor

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