Changes in trauma-potentiated startle with treatment of posttraumatic stress disorder in combat Veterans

Robison-Andrew, E. Jenna; Duval, Elizabeth R.; Nelson, C. Beau; Echiverri-Cohen, Aileen; Giardino, Nicholas D.; Defever, Andrew M.; Norrholm, Seth D.; Jovanović, Tanja; Rothbaum, Barbara O.; Liberzon, Israel; Rauch, Sheila A. M.

doi:10.1016/j.janxdis.2014.04.002

Cited by 36 publications

(39 citation statements)

References 32 publications

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“…Post-traumatic stress disorder (PTSD), for example, is characterized by symptoms that include re-experiencing, hyperarousal, and avoidance behavior triggered by a life threatening traumatic event beyond one’s control (American Psychiatric Association, 2000). The hyperarousal often observed in PTSD appears to be due to insufficient top-down regulatory control that results in hypersensitivity of subcortical brain areas (e.g., the amygdala) (Briscione et al, 2014; Jovanovic and Ressler, 2010; Milad et al, 2009; Rauch et al, 2006; Robison-Andrew et al, 2014). Further, PTSD is often associated with hypoactivation of the vmPFC and hippocampus (Bremner et al, 2004; Haas et al, 2010; Milad et al, 2009; Rauch et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Controllability modulates the neural response to predictable but not unpredictable threat in humans

et al. 2015

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Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threat may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (Controllable Condition; CC), but not the other group (Uncontrollable Condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

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Section: Discussionmentioning

confidence: 99%

Controllability modulates the neural response to predictable but not unpredictable threat in humans

et al. 2015

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“…Virtual reality methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of stressor-, trauma-, and anxiety-related disorders such as PTSD for more than a decade (Difede et al, 2007; Rizzo et al, 2010; Rothbaum, Hodges, Ready, Graap, & Alarcon, 2001). Virtual reality exposure (VRE) therapy is believed to foster engagement and elevate patient arousal (Robison-Andrew et al, 2014) through the inclusion of computer-generated simulations of trauma-related stimuli that span sensory modalities, including the ambient sights, sounds, smells, and tactile stimuli present during a traumatic event. In addition to its clinical impact, VR technology has also been used successfully to elicit robust fear reactions in patients with anxiety disorders (Diemer, Muhlberger, Pauli, & Zwanzger, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…More recently, psychophysiological measures have been employed as complementary assessment tools for use in traumatized populations presenting with PTSD symptoms (Costanzo et al, 2014; Griffin, Resick, & Galovski, 2012; Rabe, Dorfel, Zollner, Maercker, & Karl, 2006; Rhudy et al, 2010; Robison-Andrew et al, 2014; Rothbaum et al, 2014; Roy et al, 2013). The addition of psychophysiological indices, such as heart rate (HR), skin conductance (SC) and electromyography (EMG) responses to trauma-related cues can provide the potential prediction of treatment outcome, objective assessments of treatment outcome, and evidence of the underlying biological changes that accompany successful PTSD treatment.…”

Section: Introductionmentioning

confidence: 99%

“…More recent investigations have explored acoustic startle responses to trauma-related stimuli (termed trauma-potentiated startle) within the presentation of a virtual reality environment (Costanzo et al, 2014; Robison-Andrew et al, 2014; Roy et al, 2013). Robison-Andrew et al (2014) reported that combat veterans who responded well to prolonged exposure therapy (defined as a >50% reduction in their CAPS score over the course of treatment) showed an initial increase in trauma-potentiated startle followed by a significant decrease in startle responses to trauma-related cues compared to veterans who did not respond to treatment.…”

Section: Introductionmentioning

confidence: 99%

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Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

Norrholm

Jovanović

Gerardi

et al. 2016

Behaviour Research and Therapy

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Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients’ level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS).

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“…Effects of behavioral therapy on conditioned fear are also relatively untested. One small study found no significant reductions in potentiated startle to trauma-related cues after exposure therapy despite >50 % reduction in symptoms (Robison-Andrew et al 2014); however, another larger study did find that exposure therapy reduced trauma-potentiated startle . Overall, the evidence for predictive validity in terms of sensitivity to SSRI treatment is suggestive, but there are clear nuances to the parameters and dosing strategy that must be considered if these models are to be used.…”

Section: Is Conditioned Fear Responding Sensitive To Drugs That Are Ementioning

confidence: 98%

On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development

Risbrough

Glenn²,

Baker

2015

Current Topics in Behavioral Neurosciences

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The use of quantitative, laboratory-based measures of threat in humans for proof-of-concept studies and target development for novel drug discovery has grown tremendously in the last 2 decades. In particular, in the field of posttraumatic stress disorder (PTSD), human models of fear conditioning have been critical in shaping our theoretical understanding of fear processes and importantly, validating findings from animal models of the neural substrates and signaling pathways required for these complex processes. Here, we will review the use of laboratorybased measures of fear processes in humans including cued and contextual conditioning, generalization, extinction, reconsolidation, and reinstatement to develop novel drug treatments for PTSD. We will primarily focus on recent advances in using behavioral and physiological measures of fear, discussing their sensitivity as biobehavioral markers of PTSD symptoms, their response to known and novel PTSD treatments, and in the case of d-cycloserine, how well these findings have translated to outcomes in clinical trials. We will highlight some gaps in the literature and needs for future research, discuss benefits and limitations of these outcome measures in designing proof-of-concept trials, and offer practical guidelines on design and interpretation when using these fear models for drug discovery.

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Changes in trauma-potentiated startle with treatment of posttraumatic stress disorder in combat Veterans

Cited by 36 publications

References 32 publications

Controllability modulates the neural response to predictable but not unpredictable threat in humans

Controllability modulates the neural response to predictable but not unpredictable threat in humans

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

On the Road to Translation for PTSD Treatment: Theoretical and Practical Considerations of the Use of Human Models of Conditioned Fear for Drug Development

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