Exposure Therapy,<scp>d</scp>-Cycloserine, and Functional Magnetic Resonance Imaging in Patients With Snake Phobia

Nave, Andrea M.; Tolin, David F.; Stevens, Michael C.

doi:10.4088/jcp.11m07564

Cited by 47 publications

(36 citation statements)

References 51 publications

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“…A cellular target of particular interest is the N-methyl-D-aspartate (NMDA) glutamate receptor, which supports the process of long-term synaptic potentiation thought to underlie the new associative learning that occurs during extinction (Orsini & Maren 2012; Myers and Davis 2007). Indeed, a large body of literature indicates that administration of the partial NMDA agonist D-cycloserine (DCS) in conjunction with exposure therapy facilitates reductions in abnormal fear and anxiety in human clinical populations (Difede, et al, 2013; Ressler et al, 2004; Hoffmann et al, 2006; Guastella, Richardson et al, 2008; Nave et al, 2012). Early findings in rodents have also demonstrated that DCS can facilitate extinction when administered before or after exposure to fearful cues (Walker, Ressler, Lu & Davis 2002; Ledgerwood, Richardson, Cranney 2003), reduce the reinstatement of fear (Ledgerwood, Richardson, and Cranney 2004), and aid the generalization of extinction to a second non-extinguished cue (Ledgerwood, Richardson and Cranney 2005).…”

Section: Introductionmentioning

confidence: 99%

Opposing effects of d-cycloserine on fear despite a common extinction duration: Interactions between brain regions and behavior

Bolkan

Lattal

2014

Neurobiology of Learning and Memory

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A number of studies have reported that D-cycloserine (DCS), a partial agonist of the N-methyl-D-aspartate glutamate receptor, can facilitate the loss of conditioned fear if it is administered during an extinction trial. Here we examine the effects of DCS injected into the hippocampus or amygdala on extinction of context-evoked freezing after contextual fear conditioning in C57BL/6 mice. We find that DCS administered prior to an extinction session decreased freezing from the outset of the session regardless of which brain region was targeted. Retention tests revealed opposite effects on fear expression despite identical behavioral treatments: intra-hippocampal DCS inhibited fear expression while intra-amygdala DCS potentiated fear expression. Following post-extinction session injections of DCS, we found a similar though less pronounced effect. Closer inspection of the data revealed that the effects of DCS interacted with the behavior of the subjects during extinction. Intra-hippocampal injections of DCS enhanced extinction in those mice that showed the greatest amount of within-session extinction, but had less pronounced effects on mice that showed the least within-session extinction. Intra-amygdala injections of DCS impaired extinction in those mice that showed the least within-session, but there was some evidence that the effect in the amygdala did not depend on behavior during extinction. These findings demonstrate that even with identical extinction preparations and trial durations, the effects of DCS administered into the hippocampus and amygdala can heavily depend on the organism’s behavior during the extinction session. The broader implication of these findings is that the effects of pharmacological treatments designed to enhance extinction by targeting hippocampal or amygdalar processes may depend greatly on the responsivity of the subject to the behavioral treatment.

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Section: Introductionmentioning

confidence: 99%

Opposing effects of d-cycloserine on fear despite a common extinction duration: Interactions between brain regions and behavior

Bolkan

Lattal

2014

Neurobiology of Learning and Memory

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“…Moreover, participants receiving DCS-augmented exposures also exhibited expedited treatment gains relative to placebo [32]. Similar findings for an expedited therapeutic benefit were observed among DCS-enhanced exposures for ophidiophobia (fear of snakes) as evidenced by shorter time to complete a 13-step exposure hierarchy [36], as well as enhanced therapeutic outcome after DCS-augmented subliminal exposures for sub-threshold arachnophobia (fear of spiders) as evidenced by a significantly lower rating of disgust [35]. Countering these findings, Guastella et al [34] found no enhanced benefit of DCS-augmented exposures among individuals with sub-threshold arachnophobia.…”

Section: Introductionmentioning

confidence: 81%

“…Translated into a therapeutic context, these findings suggest that learned fear memories can be updated with new information during specific time periods that can allow practitioners to maximize the therapeutic effects of exposure-based treatments. Randomized controlled trials have examined the benefit of DCS-augmented exposure-based treatment across specific phobias (e.g., acrophobia [32,33], arachnophobia [34,35], ophidiophobia [36]), PD [37,38], SAD [39–42], OCD [43–48], and PTSD [49–52]. Table 1 presents the characteristics and findings from RCTs that have evaluated DCS in the context of exposure-based interventions.…”

Section: Introductionmentioning

confidence: 99%

Enhancing exposure therapy for anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder

McGuire¹,

Lewin²,

Storch³

2014

Expert Review of Neurotherapeutics

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Translating findings from basic science, several compounds have been identified that may enhance therapeutic outcomes and/or expedite treatment gains when administered alongside exposure-based treatments. Four of these compounds (referred to as cognitive enhancers) have been evaluated in the context of randomized controlled trials for anxiety disorders (e.g., specific phobias, panic disorder, social anxiety disorder), obsessive compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). These cognitive enhancers include D-cycloserine, yohimbine hydrochloride, glucocorticoids and cortisol, and brain derived neurotrophic factor. There is consistent evidence that cognitive enhancers can enhance therapeutic outcomes and/or expedite treatment gains across anxiety disorders, OCD, and PTSD. Emerging evidence has highlighted the importance of within-session fear habituation and between-session fear learning, which can either enhance fear extinction or reconsolidate of fear responses. Although findings from these trials are promising, there are several considerations that warrant further evaluation prior to wide-spread use of cognitive enhancers in exposure-based treatments. Consistent trial design and large sample sizes are important in future studies of cognitive enhancers.

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“…In SAD, two randomized, double-blind, placebo-controlled trials suggest that DCS (50 mg) administered adjunctively to exposure therapy is associated with beneficial effects in reducing symptom severity, altering dysfunctional cognitions and reducing overall impairment [70,71]. In individuals with specific phobia, augmentation of exposure therapy with DCS (50 mg) was found to lead to changes in prefrontal (especially ventromedial) cortex response to phobic stimuli [72], but these findings may not necessarily translate to patients with SAD.…”

Section: Potential Novel Pharmacological Treatmentsmentioning

confidence: 99%

Pharmacological Treatment of Social Anxiety Disorder

Masdrakis

Turic²,

Baldwin³

2013

Modern Trends in Psychiatry

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Social anxiety disorder (social phobia) is a common and typically long-standing medical condition, characterized by an excessive fear of being observed or evaluated negatively in social or performance situations. Efficacious interventions in acute treatment include cognitive behavioural therapy and a range of medications including many antidepressants, some benzodiazepines and anticonvulsants, and the antipsychotic olanzapine. Most studies report no significant differences in overall efficacy or tolerability between active compounds. Responders to previous acute treatment benefit from continuing active medication for 6 months. Evidence of a dose-response relationship with antidepressant drugs is inconsistent, though only higher doses of pregabalin are efficacious. Switching between treatments with proven efficacy may be helpful. Augmentation of a selective serotonin reuptake inhibitor with buspirone or clonazepam can be beneficial. It is unlikely that combining pharmacotherapy with psychotherapy results in greater overall efficacy compared to either treatment given alone. Proof-of-concept and other preliminary studies suggest the efficacy of psychotherapy can be enhanced through prior administration of D-cycloserine, cannabidiol, or oxytocin.

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Exposure Therapy,d-Cycloserine, and Functional Magnetic Resonance Imaging in Patients With Snake Phobia

Abstract: ClinicalTrials.gov identifier: NCT01450306.

Cited by 47 publications

References 51 publications

Opposing effects of d-cycloserine on fear despite a common extinction duration: Interactions between brain regions and behavior

Opposing effects of d-cycloserine on fear despite a common extinction duration: Interactions between brain regions and behavior

Enhancing exposure therapy for anxiety disorders, obsessive-compulsive disorder and post-traumatic stress disorder

Pharmacological Treatment of Social Anxiety Disorder

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