Regional cerebral glucose metabolism differentiates danger- and non-danger-based traumas in post-traumatic stress disorder

Abstract

Post-traumatic stress disorder (PTSD) is presumably the result of life threats and conditioned fear. However, the neurobiology of fear fails to explain the impact of traumas that do not entail threats. Neuronal function, assessed as glucose metabolism with (18)fluoro-deoxyglucose positron emission tomography, was contrasted in active duty, treatment-seeking US Army Soldiers with PTSD endorsing either danger- (n = 19) or non-danger-based (n = 26) traumas, and was compared with soldiers without PTSD (Combat Controls, n = 26) and Civilian Controls (n = 24). Prior meta-analyses of regions associated with fear or trauma script imagery in PTSD were used to compare glucose metabolism across groups. Danger-based traumas were associated with higher metabolism in the right amygdala than the control groups, while non-danger-based traumas associated with heightened precuneus metabolism relative to the danger group. In the danger group, PTSD severity was associated with higher metabolism in precuneus and dorsal anterior cingulate and lower metabolism in left amygdala (R(2 )= 0.61). In the non-danger group, PTSD symptom severity was associated with higher precuneus metabolism and lower right amygdala metabolism (R(2 )= 0.64). These findings suggest a biological basis to consider subtyping PTSD according to the nature of the traumatic context.

Danger- and non-danger-based stressors and their relations to posttraumatic deprecation or growth in Norwegian veterans deployed to Afghanistan

“…Neuro-imaging studies have indicated that dangerbased and non-danger-based stressors activate quite different locations in the brain. Ramage et al (2015) found that only danger-based stressors elicited increased metabolic activity in the fear circuitry involving the amygdalae. In contrast, the non-danger-based stressors increased the metabolism in the precuneus, a part of the medial parietal cortex involved in episodic memory and self-processing operations (Cavanna & Trimble, 2006).…”

“…Furthermore, several studies suggest that various types of traumatic stressors may produce different symptomatic outcomes. Generally, danger-based stressors are associated with a hyperarousal symptom cluster, while non-danger-based stressors seem associated rather with a depression symptom cluster (Pietrzak et al, 2011;Ramage et al, 2015;Shea et al, 2017;Stein et al, 2012). Moreover, non-danger-based stressors may precipitate more posttraumatic distress than the dangerbased stressors (Litz et al, 2009;Nash et al, 2010;Ramage et al, 2015).…”

“…Being involved in actions resulting in civilian casualties due to collateral damage is one example of a moral stressor. Distinctions that are more general have also been made, categorizing incidents involving personal threat as Danger-Based Stress, and moral stressors as well as witnessing incidents together as Non-Danger-Based Stress (Ramage et al, 2015).…”

“…At the outset, it consisted of 23 items of typical traumatic events that were likely to occur during deployment. Based on literature reviews (Breslau & Davis, 1987;Fontana et al, 1992;Jordan, Eisen, Bolton, Nash, & Litz, 2017;Litz et al, 2009;Shea et al, 2017;Stein et al, 2012;Vogt, Proctor, King, King, & Vasterling, 2008), we selected a set of items that covered danger-based or non-danger-based stressors (Ramage et al, 2015). The danger-based stressors were related to Personal Threat incidents, while the non-danger-based stressors consisted of Moral Challenges (Litz et al, 2009;Stein et al, 2012) and Witnessing incidents (Green, Grace, Lindy, Gleser, & Leonard, 1990).…”

Long-Term Clinical and Neuronuclear Imaging Sequelae of Cancer Therapy, Trauma, and Brain Injury

“…In an 18 F-FDG PET study on active-duty treatment-seeking U.S. army soldiers with PTSD who experienced danger-based trauma, decreased metabolism in the left amygdala was associated with PTSD severity. In PTSD patients without danger-based trauma, decreased metabolism in the right amygdala was associated with PTSD severity (46). Recent studies have also explored discrete amygdala subregions involved in encoding of emotional events, including the basolateral subdivision and the centromedial amygdala ( The medial prefrontal cortex has been consistently established as a region involved in emotional regulation, and its failure to inhibit the amygdala in PTSD has been thought to lead to impaired fear extinction.…”