Traditionally, microglia have been considered to act as macrophages of the central nervous system. While this concept still remains true it is also becoming increasingly apparent that microglia are involved in a host of nonimmunological activities, such as monitoring synaptic function and maintaining synaptic integrity. It has also become apparent that microglia are exquisitely sensitive to perturbation by environmental challenges. The aim of the current review is to critically examine the now substantial literature that has developed around the ability of acute, sub-chronic and chronic stressors to alter microglial structure and function. The vast majority of studies have demonstrated that stress promotes significant structural remodelling of microglia, and can enhance the release of pro-inflammatory cytokines from microglia. Mechanistically, many of these effects appear to be driven by traditional stress-linked signalling molecules, namely corticosterone and norepinephrine. The specific effects of these signalling molecules are, however, complex as they can exert both inhibitory and suppressive effects on microglia depending upon the duration and intensity of exposure. Importantly, research has now shown that these stress-induced microglial alterations, rather than being epiphenomena, have broader behavioural implications, with the available evidence implicating microglia in directly regulating certain aspects of cognitive function and emotional regulation.
Potentially morally injurious events (PMIEs) entail acts of commission (e.g., cruelty, proscribed or prescribed violence) or omission (e.g., high stakes failure to protect others) and bearing witness (e.g., to grave inhumanity, to the gruesome aftermath of violence), or being the victim of others' acts of commission (e.g., high stakes trust violations) or omission (e.g., being the victim of grave individual or systemic failures to protect) that transgress deeply held beliefs and expectations about right and wrong. Although there is a proliferation of interest in moral injury (the outcome associated with exposure to PMIEs), there has been no operational definition of the putative syndrome and no standard assessment scheme or measure, which has hampered research and care in this area. We describe an international effort to define the syndrome of moral injury and develop and validate the Moral Injury Outcome Scale (MIOS) in three stages. To ensure content validity, in Stage I, we conducted interviews with service members, Veterans, and clinicians/Chaplains in each country, inquiring about the lasting impact of PMIEs. Qualitative analysis yielded six operational definitions of domains of impact of PMIEs and components within domains that establish the parameters of the moral injury syndrome. From the domain definitions, we derived an initial pool of scale items. Stage II entailed scale refinement using factor analytic methods, cross-national invariance testing, and internal consistency reliability analyses of an initial 34-item MIOS. A 14-item MIOS was invariant and reliable across countries and had two factors: Shame-Related (SR) and Trust-Violation-Related (TVR) Outcomes. In Stage III, MIOS total and subscale scores had strong convergent validity, and PMIE-endorsers had substantially higher MIOS scores vs. non-endorsers. We discuss and contextualize the results and describe research that is needed to substantiate these inaugural findings to further explore the validity of the MIOS and moral injury, in particular to examine discriminant and incremental validity.
Post-traumatic stress disorder (PTSD) is a common mental health condition that requires exposure to a traumatic event. This provides unique opportunities for prevention that are not available for other disorders. The aim of this review was to undertake a systematic review and evaluation of randomized controlled trials (RCTs) of interventions designed to prevent PTSD in adults. Searches involving Cochrane, Embase, Medline, PsycINFO, PILOTS and Pubmed databases were undertaken to identify RCTs of pre-incident preparedness and post-incident interventions until May 2019. Six pre-incident and 69 post-incident trials were identified that could be included in meta-analyses. The overall quality of the evidence was low. There was emerging evidence that some interventions may be helpful but an absence of evidence for any intervention that can be strongly recommended for universal, selected or indicated prevention before or within the first three months of a traumatic event. The strongest results were found for cognitive-behavioural therapy with a trauma focus (CBT-T) in individuals with a diagnosis of acute stress disorder which supports calls to detect and treat individuals with significant symptoms rather than providing blanket preventative interventions. Further research is required to optimally configure existing interventions with some evidence of effect and to develop novel interventions to address this major public health issue.