Inflammation in Posttraumatic Stress Disorder: Dysregulation or Recalibration?

Abstract

Despite ample experimental data indicating a role of inflammatory mediators in the behavioral and neurobiological manifestations elicited by exposure to physical and psychologic stressors, causative associations between systemic low-grade inflammation and central nervous system inflammatory processes in posttraumatic stress disorder (PTSD) patients remain largely conceptual. As in other stress-related disorders, pro-inflammatory activity may play an equivocal role in PTSD pathophysiology, one that renders indiscriminate employment of anti-inflammatory agents of questionable relevance. In fact, as several pieces of preclinical and clinical research convergingly suggest, timely and targeted potentiation rather than inhibition of inflammatory responses may actually be beneficial in patients who are characterized by suppressed microglia function in the face of systemic low-grade inflammation. The deleterious impact of chronic stress-associated inflammation on the systemic level may, thus, need to be held in context with the - often not readily apparent - adaptive payoffs of low-grade inflammation at the tissue level.

Keywords: Posttraumatic stress disorder (PTSD); anti-inflammatory agents.; immune system; inflammation; microglia; neurobiology.

Fig. (1)

Proposed model represents the dynamic alterations in systemic inflammation and microglia activation status in PTSD based on the type of response in the periphery (A) and within the CNS (B). Non-resolving, low-grade inflammation in the chronic post-trauma phase may be associated with either an excessive or a subnormal inflammatory response in the acute post-trauma phase in both compartments. However, an excessive or subnormal CNS inflammatory response in the acute phase may also pave the way to a premature suppression of microglia activity. Accordingly, both anti-inflammatory approaches (acutely and subacutely post-trauma) and pro-inflammatory approaches (in the form of either pre-trauma immunization or post-trauma boosters) may be therapeutically pertinent, depending on whether the microglia compartment is in a state of overactivation or suppression, respectively.

Fig. (2)

Potential therapeutic and/or prophylactic immunostimulatory approaches leading to enhanced stress resilience. References are provided in the text. Abbreviations: LPS: lipopolysaccharide; CNS: central nervous system; Treg: regulatory T cells; GC: glucocorticoid.