The effects of trauma on brain and body: A unifying role for the midbrain periaqueductal gray

Abstract

Post-traumatic stress disorder (PTSD), a diagnosis that may follow the experience of trauma, has multiple symptomatic phenotypes. Generally, individuals with PTSD display symptoms of hyperarousal and of hyperemotionality in the presence of fearful stimuli. A subset of individuals with PTSD; however, elicit dissociative symptomatology (i.e., depersonalization, derealization) in the wake of a perceived threat. This pattern of response characterizes the dissociative subtype of the disorder, which is often associated with emotional numbing and hypoarousal. Both symptomatic phenotypes exhibit attentional threat biases, where threat stimuli are processed preferentially leading to a hypervigilant state that is thought to promote defensive behaviors during threat processing. Accordingly, PTSD and its dissociative subtype are thought to differ in their proclivity to elicit active (i.e., fight, flight) versus passive (i.e., tonic immobility, emotional shutdown) defensive responses, which are characterized by the increased and the decreased expression of the sympathetic nervous system, respectively. Moreover, active and passive defenses are accompanied by primarily endocannabinoid-and opioid-mediated analgesics, respectively. Through critical review of the literature, we apply the defense cascade model to better understand the pathological presentation of defensive responses in PTSD with a focus on the functioning of lower-level midbrain and extended brainstem systems. K E Y W O R D Sbrainstem, dissociation, periaqueductal gray, PTSD, trauma | INTRODUC TI ONIn this review, we integrate literature from trauma experiences, the defense cascade, and the threat-response neurocircuitry within a framework of post-traumatic stress disorder (PTSD). We begin by introducing the concepts of the hypothalamic-pituitary-adrenal (HPA) axis, general PTSD, and defensive responses. Following these primers, we discuss the influences of trauma onset and prolonged exposure to trauma and their effects on the development of PTSD and the dissociative subtype of PTSD. Next, we introduce the defense cascade model and its underlying neurocircuitry as described in the animal literature and relate it to PTSD. In addition, we discuss the current state of the neuroimaging literature, which Edited by Sandra Chanraud.All peer review communications can be found with the online version of the article. | 1111TERPOU ET al. suggests that functional alterations are detectable in the midbrain of individuals with PTSD and its dissociative subtype as compared to healthy controls. We conclude by presenting directions for future research and the clinical implications for treatment of persons with PTSD that arise from this review of the extant literature.

Back to the Basics: Resting State Functional Connectivity of the Reticular Activation System in PTSD and its Dissociative Subtype

“…Resting state functional connectivity was analyzed using a region-ofinterest (ROI) approach, with a priori brain regions, namely, the midbrain, the amygdala, and the ventromedial prefrontal cortex, selected due to their relation to innate threat processing and arousal. 18,19,57,[60][61][62][63][91][92][93] We also included the thalamus, as it serves as a major hub in transmitting information from the RAS to cortical and to subcortical structures. Bilateral amygdala, thalamus, and ventromedial prefrontal masks were created with the automated anatomical labeling atlas, 94 which was implemented in the WFU PickAtlas software.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Importantly, emerging evidence has underscored the importance of incorporating deep-layer midbrain/brainstem neural circuits into the neurobiological framework of PTSD. 1,2,[15][16][17][18][19] The reticular activation system (RAS) serves a fundamental role toward the gating of salient, environmental information to higher order, cortical brain structures to facilitate the generation and the maintenance of an arousal state. [20][21][22][23][24][25][26] Moreover, the RAS has also been linked to support the formation of action-outcome associations in the brain.…”

Inflammation and Trauma-Related Psychopathology in Syrian and Iraqi Refugees

“…Trauma type may also have a role, and there may be differences between refugee populations exposed to war trauma compared to other groups more commonly assessed in the literature, including victims of motor vehicle accidents, assault/abuse, and combat veterans. Type of trauma exposure is critical, as chronic, interpersonal traumas may yield more passive, blunted behavioral and sympathetic responses, while acute, non-interpersonal traumas may yield more active, activating behavioral and sympathetic responses [9]. Finally, uniqueness of our findings in a novel subject population with dominant literature focused on Caucasian and Black/African American racial backgrounds signifies the importance of larger future studies of inflammation and trauma in other ethnic and racial groups; indeed some of the relations we found between psychopathology and inflammatory variables were more akin to findings from a sample of Iraqi individuals [37].…”

“…Acute activation of this system is adaptive, however chronic activation is maladaptive [8]. After the traumatic event has ceased, these physiological responses may become sensitized and maladaptive such that stress and trauma-related stimuli can elicit them in the absence of danger [9]. For example, individuals may show attention bias towards threatening stimuli and become hypervigilant and aroused [9].…”

“…After the traumatic event has ceased, these physiological responses may become sensitized and maladaptive such that stress and trauma-related stimuli can elicit them in the absence of danger [9]. For example, individuals may show attention bias towards threatening stimuli and become hypervigilant and aroused [9]. Chronic activation of the SAM and immune system results in diminished vaccine responses [10], exacerbated viral and bacterial pathogenesis [11], stunted wound healing [12], alteration in autoimmune diseases, and exacerbated psychiatric susceptibility and severity [13].…”