Biological and Symptom Changes in Posttraumatic Stress Disorder Treatment: A Randomized Clinical Trial

Rauch, Sheila A. M.; King, Anthony P.; Abelson, James L.; Tuerk, Peter W.; Smith, Erin R.; Rothbaum, Barbara O.; Clifton, Erin G.; Defever, B S Andrew; Liberzon, Israel

doi:10.1002/da.22331

Cited by 75 publications

(48 citation statements)

References 36 publications

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“…Although these studies used unstructured psychotherapeutic approaches, and not exposure therapy, the observations in the present study support the hypothesis that reduction of PTSD symptoms by MDMA-assisted psychotherapy is facilitated by enhancing the extinction of the fear response to memories for trauma. Indeed, improvements in PTSD symptoms are achieved by exposure-based therapies that rely on principles of extinction learning (Rauch et al 2015). However, a portion of patients remain unresponsive to that treatment.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

et al. 2017

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Rationale 3,4-methylenedioxymethamphetamine (MDMA) persistently improves symptoms of post-traumatic stress disorder (PTSD) when combined with psychotherapy. Studies in rodents suggest that these effects can be attributed to enhancement of fear memory extinction. Therefore, MDMA may improve the effects of exposure-based therapy for PTSD; particularly in treatment-resistant patients. However, given MDMA's broad pharmacological profile, further investigation is warranted before moving to a complex clinical population. Objectives We aimed to inform clinical research by providing a translational model of MDMA's effect, and elucidating monoaminergic mechanisms through which MDMA enhances fear extinction. Methods We explored the importance of monoamine transporters targeted by MDMA to fear memory extinction, as measured by reductions in conditioned freezing and fear-potentiated startle (FPS) in mice. Mice were treated with selective inhibitors of individual monoamine transporters prior to combined MDMA treatment and fear extinction training. Results MDMA enhanced the lasting extinction of FPS. Acute and chronic treatment with a 5-HT transporter (5-HTT) inhibitor blocked MDMA's effect on fear memory extinction. Acute inhibition of dopamine (DA) and norepinephrine (NE) transporters had no effect. 5-HT release alone did not enhance extinction. Blockade of MDMA's effect by 5-HTT inhibition also downregulated 5-HT2A-mediated behavior, and 5-HT2A antagonism disrupted MDMA's effect on extinction. Conclusions We validate enhancement of fear memory extinction by MDMA in a translational behavioral model, and reveal the importance of 5-HTT and 5-HT2A receptors to this effect. These observations support future clinical research of MDMA as an adjunct to exposure therapy, and provide important pharmacological considerations for clinical use in a population frequently treated with 5-HTT inhibitors.

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Section: Discussionmentioning

confidence: 99%

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

et al. 2017

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“…Overgeneralization is not only associated with the onset and maintenance of PTSD, but treatment-related reductions in overgeneralization have also been shown to predict improvement in PTSD symptoms in adult and adolescent populations (McLean et al, 2015; Rauch et al, 2015; Sobel et al, 2009; Zalta et al, 2013). In addition, we previously reported (Ready et al, 2015) that more overgeneralization in sessions during the narrative phase of TF-CBT for children and adolescents predicted worse outcomes on more broadband measures of functioning, internalizing at posttreatment and externalizing symptoms over the follow-up, though not on PTSD-specific symptoms at either assessment point (Ready et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…Changes in overgeneralized trauma-related beliefs precede and predict PTSD symptom change in prolonged exposure for adults (Rauch et al, 2015; Zalta et al, 2013) and adolescents (McLean, Yeh, Rosenfield, & Foa, 2015) and in cognitive therapy for adult PTSD (Kleim et al, 2013). Decreases in overgeneralized statements in trauma impact statements were also associated with change in PTSD symptoms from pre to posttreatment in cognitive processing therapy (CPT) for adults (Sobel, Resick, & Rabalais, 2009).…”

Section: Unproductive Processing In Ptsdmentioning

confidence: 99%

Constructive and Unproductive Processing of Traumatic Experiences in Trauma-Focused Cognitive-Behavioral Therapy for Youth

et al. 2017

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Although there is substantial evidence to support the efficacy of cognitive-behavioral treatments (CBT) for posttraumatic stress disorder (PTSD), there is some debate about how these treatments have their effects. Modern learning theory and cognitive and emotional processing theories highlight the importance of reducing avoidance, facilitating the constructive processing of feared experiences, and strengthening new inhibitory learning. We examined variables thought to be associated with unproductive and constructive processing of traumatic experiences in a sample of 81 youth with elevated PTSD symptoms, who received Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) for abuse or traumatic interpersonal loss. Sessions during the trauma narrative phase of TF-CBT were coded for indicators of unproductive processing (overgeneralization, rumination, avoidance) and constructive processing (decentering, accommodation of corrective information), as well as levels of negative emotion. In previous analyses of this trial (Ready et al., 2015), more overgeneralization during the narrative phase predicted less improvement in internalizing symptoms at posttreatment and a worsening of externalizing symptoms over the 12-month follow-up. In contrast, more accommodation predicted improvement in internalizing symptoms and also moderated the negative effects of overgeneralization on internalizing and externalizing symptoms. The current study examined correlates of overgeneralization and accommodation. Overgeneralization was associated with more rumination, less decentering, and more negative emotion, suggesting immersion in trauma-related material. Accommodation was Please address correspondence to Adele Hayes, Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, USA. ahayes@udel.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conflict of Interest No conflicts of interest HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript associated with less avoidance and more decentering, suggesting a healthy distance from traumarelated material that might allow for processing and cognitive change. Decentering also predicted improvement in externalizing symptoms at posttreatment. Rumination and avoidance showed important associations with overgeneralization and accommodation, respectively, but did not predict treatment outcomes. This study identifies correlates of overgeneralization and accommodation that might shed light on how these variables relate to unproductive and constructive processing of traumatic experiences. Key...

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“…For example, Owens, Cox, and Chard (2008) found that pre-treatment cognitions predicted change in PTSD symptoms following intensive CPT. Similarly, Foa and Rauch (2004) and Rauch et al (2015) found that change in cognitions was related to change in PTSD symptoms following PE or PE with cognitive restructuring. Other studies have found relationships between changes in cognitions and changes in PTSD symptoms following CPT (Gallagher & Resick, 2012; Iverson et al, 2015; Sobel et al, 2009) and other cognitive behavioral interventions (Karl et al, 2009).…”

mentioning

confidence: 90%

Trauma cognitions are related to symptoms up to 10 years after cognitive behavioral treatment for posttraumatic stress disorder.

Scher

Suvak

Resick

2017

Psychological Trauma: Theory, Research, Practice, and Policy

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Objectives This study examined 1) relationships between trauma-related cognitions and Posttraumatic Stress Disorder (PTSD) symptoms from pre-treatment through a long-term period following cognitive behavioral therapy (CBT) for PTSD and 2) whether these relationships were impacted by treatment type. Method Participants were 171 women randomized into treatment for PTSD following rape. Measures of self-reported trauma-related cognitions and interviewer-assessed PTSD symptoms (i.e., Posttraumatic Maladaptive Beliefs Scale, Trauma-Related Guilt Inventory, and Clinician-Administered PTSD Scale) were obtained at pre-treatment, post-treatment, and 3-month, 9-month, and 5–10 year follow-ups. Multilevel regression analyses were used to examine relationships between trauma-related cognitions and PTSD symptoms throughout the study period and whether these relationships differed as a function of treatment type (i.e., Cognitive Processing Therapy or Prolonged Exposure). Results Initial multilevel regression analyses that examined mean within-participant associations suggested that beliefs regarding Reliability and Trustworthiness of Others, Self-Worth and Judgment, Threat of Harm, and Guilt were related to PTSD symptoms throughout follow-up. Growth curve modeling suggested that patterns of belief change throughout follow-up were similar to those previously observed in PTSD symptoms over the same time period. Finally, multilevel mediation analyses that incorporated time further suggested that change in beliefs was related to change in symptoms throughout follow-up. With one minor exception, relationships between beliefs and symptoms were not moderated by treatment type. Conclusions These data suggest that trauma-related cognitions are a potential mechanism for long-term maintenance of treatment gains following CBT for PTSD. Moreover, these cognitions may be a common, rather than specific, treatment maintenance mechanism.

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Biological and Symptom Changes in Posttraumatic Stress Disorder Treatment: A Randomized Clinical Trial

Cited by 75 publications

References 36 publications

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

Inhibition of serotonin transporters disrupts the enhancement of fear memory extinction by 3,4-methylenedioxymethamphetamine (MDMA)

Constructive and Unproductive Processing of Traumatic Experiences in Trauma-Focused Cognitive-Behavioral Therapy for Youth

Trauma cognitions are related to symptoms up to 10 years after cognitive behavioral treatment for posttraumatic stress disorder.

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