Fear potentiation is associated with hypothalamic–pituitary–adrenal axis function in PTSD (original) (raw)
Related papers
Psychiatry Research, 2009
One of the central problems in posttraumatic stress disorder (PTSD) is the inability to suppress fear even under safe conditions. The neural underpinnings of fear is a clinically relevant issue that is poorly understood. This study assessed fear potentiation and fear inhibition using fear-potentiated startle in a conditional discrimination procedure (AX+/BX-). We hypothesized that patients with PTSD would show normal fear potentiation and impaired fear inhibition. 28 healthy volunteers and 27 PTSD patients (14 with low current symptoms, 13 with high current symptoms) were presented with one set of colored lights (AX trials) paired with aversive air blasts to the throat, and a different series of lights (BX trials) presented without air blasts. We then presented A and B together (AB trials) to see whether B would inhibit fear potentiation to A. All groups showed robust fear potentiation in that they had significantly greater startle magnitude on AX trials compared to noise alone trials. However, the high symptom PTSD group did not show fear inhibition: these subjects had significantly greater fear potentiation on the AB trials than both the controls and the low symptom PTSD patients.
Psychoneuroendocrinology, 2011
This study examined the effects of oral administration of 20 mg hydrocortisone on baseline and fear-potentiated startle in 63 male veterans with or without PTSD. The procedure was based on a two-session, within-subject design in which acoustic startle eyeblink responses were recorded during intervals of threat or no threat of electric shock. Results showed that the magnitude of the difference between startle responses recorded during anticipation of imminent shock compared to "safe" periods was reduced after hydrocortisone administration relative to placebo. This effect did not vary as a function of PTSD group nor were there were any significant group differences in other indices startle amplitude. Findings suggest that the acute elevations in systemic cortisol produced by hydrocortisone administration may have fear-inhibiting effects. This finding may have implications for understanding the role of hypothalamic-pituitary-adrenal (HPA)-axis function in vulnerability and resilience to traumatic stress.
Impaired fear inhibition is a biomarker of PTSD but not depression
Depression and Anxiety, 2010
Background-A central problem in posttraumatic stress disorder (PTSD) is a reduced capacity to suppress fear under safe conditions. Previously, we have shown that combat-related PTSD patients have impaired inhibition of fear-potentiated startle. Given the high comorbidity between PTSD and depression, our goal was to see whether this impairment is specific to PTSD, or a nonspecific symptom associated with both disorders.
Current Psychiatry Reports, 2013
As presently defined, post-traumatic stress disorder (PTSD) is an amalgam of symptoms falling into: re-experiencing of the trauma, avoidance of reminders of it, emotional numbing and hyperarousal. PTSD has a well-known proximate cause, commonly occurring after a life-threatening event that induces a response of intense fear, horror, and helplessness. Much of the advancement in understanding of the neurobiology of PTSD has emerged from conceptualizing the disorder as one that involves substantial dysfunction in fear processing. This article reviews recent knowledge of fear processing markers in PTSD. A systematic search was performed of reports within the specific three-year publication time period of January 2010 to December 2012. We identified a total of 31 studies reporting fear processing markers in PTSD. We further categorized them according to the following classification: (1) neural-activation markers (n=10), (2) psychophysiological markers (n=14), and (3) behavioral markers (n=7). Across most studies reviewed here, significant differences between individuals with PTSD and healthy controls were shown. Methodological, theoretical and clinical implications were discussed.
Depression and Anxiety, 2013
Background: Previous work has shown that inhibition of fear is impaired in posttraumatic stress disorder (PTSD) resulting from both civilian and combat trauma. The purpose of the present study was to investigate the inhibition of learned fear in traumatized individuals diagnosed with either acute stress disorder (ASD) or PTSD. This is the first study to use a conditioned inhibition paradigm with traumatized individuals within a month of trauma exposure. We hypothesized that impaired fear inhibition would be evident in PTSD, but not ASD. Method: Using established translational, psychophysiological methods including fear-potentiated startle, and skin conductance, we examined fear acquisition, stimulus discrimination, and the transfer of learned safety in a Croatian population with ASD or PTSD. This cross-sectional study included three age-matched groups: healthy nontrauma controls (n = 27), a group with chronic PTSD (10 or more years since trauma exposure, n = 24), and a group with ASD (30 days or less since trauma exposure, n = 27). Results: The presence of trauma-related psychopathology, whether acute or chronic, was associated with an impaired ability to transfer learned safety based on fear-potentiated startle measures, while healthy control subjects showed significant fear inhibition in the presence of the safety cue compared to the danger cue, F(1,26) = 12.64, P = .001. Conclusions: These data expand our previously observed findings of PTSD-associated fear inhibition deficits by demonstrating that trauma-related impairments in safety learning are evident within 30 days of trauma exposure.
Psychophysiology, 2019
After exposure to a traumatic event, a subset of people develop posttraumatic stress disorder (PTSD). One of the key deficits in PTSD is regulation of fear, and impaired inhibition of fearpotentiated startle has been identified as a potential physiological biomarker specific to PTSD. As part of a larger clinical trial, this study investigated the effects of a CRF receptor 1 antagonist, GSK561679, on inhibition of fear-potentiated startle during a conditional discrimination fearconditioning paradigm, termed AX+/BX-. Prior research using this paradigm has demonstrated deficits in inhibition of conditioned fear in several PTSD populations. The randomized, doubleblind, placebo-controlled clinical trial compared fear inhibition between female PTSD participants taking 350 mg/day GSK561679 (n = 47 pre, and 29 post treatment) and patients taking a placebo pill (n = 52 pre, and 30 post treatment) daily for six weeks. There was no significant difference between the two groups in their acquisition of fear or discrimination between threat and safety cues, and no pre-post treatment effect on these measures. However, there was a significant effect
Journal of Anxiety Disorders, 2014
Emotional Processing Theory proposes that habituation to trauma-related stimuli is an essential component of PTSD treatment. However, the mechanisms underlying treatment-related habituation are not well understood. We examined one psychophysiological measure that holds potential for elucidating the biological processes involved in treatment response: trauma-potentiated startle response. Seventeen OEF/OIF combat Veterans participated in the study and completed three assessments using a trauma-potentiated startle paradigm over PTSD treatment. Results revealed different patterns of traumapotentiated startle across treatment for responders and nonresponders, but no differences in within task habituation. Responders showed an increase followed by a decrease in trauma-potentiated startle, whereas nonresponders showed a relatively flat response profile. Results suggested that PTSD patients who engage with emotional content as demonstrated by greater startle reactivity may be more likely to respond to PTSD treatment. Furthermore, trauma-potentiated startle shows promise as an objective measure of psychophysiological responses involved in PTSD recovery.
Introduction 1.1 Increased defensive reactions as a sign of PTSD Post-traumatic stress disorder (PTSD) is a multi-symptom condition that includes three primary psychological features: reexperiencing, avoidance and emotional numbing, and hyperarousal (American Psychiatric Association, 2000). Historically, reexperiencing and hyperarousal have been the most studied features, from a neurobiological perspective, using various animal models. In these animal models, changes in defensive reflexive behaviors serve as the assessment measures for these symptoms; thus, both startle reactivity and freezing are now commonly used measures. Freezing behavior is advantageous because of its easy implementation; either the naked eye or an automated motor-tracking system can determine the duration and/or frequency of freezing behavior. In addition, freezing can occur in response to a specific fear-eliciting stimulus or to a fear-experienced context (Doyle & Yule, 1959; Bouton & Bolles, 1980; Fanselow, 1980). Because of these stimulus-response properties, freezing is the response commonly used to assess the experiencing of memories of conditioned stimuli that previously caused a heightened state of fear. At times, the acoustic startle response is used as an assessment of stimulus-elicited fear reactions (Davis, 1986; Hitchcock & Davis, 1987). Under this guise, similar stimuli used in conditioned freezing are experienced by the animal prior to a quick onset, relatively loud, acoustic stimulus. The result is a startle response that is enhanced over baseline levels, which is termed fear-potentiated startle. However, in the case of PTSD, arousal is not necessarily tied to a memory or triggered by an explicit learned association. There are several examples of patients with PTSD exhibiting exaggerated startle responses in the absence of a known trigger (
Revisiting the Role of the Amygdala in Posttraumatic Stress Disorder
The Amygdala - Where Emotions Shape Perception, Learning and Memories, 2017
Over the past 20 years, the reactivity of amygdala to emotive stimuli has been explored by emerging neuroimaging techniques in an effort to understand the role of amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). A fear neurocircuitry model, whereby the amygdala is hyperactive due to poor top-down control from the anterior cingulate and ventromedial prefrontal cortices, has been supported by numerous experimental studies and meta-analyses. However, this model has not always been upheld by experimental data and clinical observations. In particular, many neuroimaging studies find that the amygdala fails to activate in response to negative stimuli in individuals with PTSD. Several technical and design issues may explain disparate results regarding amygdala reactivity in PTSD. However, biological and symptom-based factors emerge as possible mediators of amygdala function in PTSD, leading to the conclusion that symptoms of emotional disengagement and dissociation are associated with amygdala hyporeactivity, and symptoms of hypervigilance/hyperarousal and problems with fear conditioning and extinction are reflected by amygdala hyperactivity. Therefore, treatment of PTSD should take into account the nature of amygdala dysfunction in the individual to optimize treatment outcomes.