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Glucocorticoids enhance extinction-based psychotherapy.

ABSTRACT: Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. Cortisol (20 mg) or placebo was administered orally 1 h before each of the treatment sessions. Subjects returned for a posttreatment assessment 3-5 d after the last treatment session and for a follow-up assessment after 1 mo. Adding cortisol to exposure therapy resulted in a significantly greater reduction in fear of heights as measured with the acrophobia questionnaire (AQ) both at posttreatment and at follow-up, compared with placebo. Furthermore, subjects receiving cortisol showed a significantly greater reduction in acute anxiety during virtual exposure to a phobic situation at posttreatment and a significantly smaller exposure-induced increase in skin conductance level at follow-up. The present findings indicate that the administration of cortisol can enhance extinction-based psychotherapy.

SUBMITTER: de Quervain DJ

PROVIDER: S-EPMC3081033 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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Glucocorticoids enhance extinction-based psychotherapy.

de Quervain Dominique J-F DJ Bentz Dorothée D Michael Tanja T Bolt Olivia C OC Wiederhold Brenda K BK Margraf Jürgen J Wilhelm Frank H FH

Proceedings of the National Academy of Sciences of the United States of America 20110328 16

Behavioral exposure therapy of anxiety disorders is believed to rely on fear extinction. Because preclinical studies have shown that glucocorticoids can promote extinction processes, we aimed at investigating whether the administration of these hormones might be useful in enhancing exposure therapy. In a randomized, double-blind, placebo-controlled study, 40 patients with specific phobia for heights were treated with three sessions of exposure therapy using virtual reality exposure to heights. C ...[more]

PMID: 21444799

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Project description:BackgroundDespite the high prevalence of major depressive disorder and the related societal burden, access to effective traditional face-to-face or video-based psychotherapy is a challenge. An alternative that offers mental health care in a flexible setting is asynchronous messaging therapy. To date, no study has evaluated its efficacy and acceptability in a randomized controlled trial for depression.ObjectiveThe aim of this study was to compare the efficacy and acceptability of message-based psychotherapy for depression to once-weekly video-based psychotherapy.MethodsIn this 2-armed randomized controlled trial, individuals (N=83) with depressive symptomatology (Patient Health Questionnaire-9 ≥10) were recruited on the internet and randomly assigned to either a message-based intervention group (n=46) or a once-weekly video-based intervention group (n=37). Patients in the message-based treatment condition exchanged asynchronous messages with their therapist following an agreed-upon schedule. Patients in the video-based treatment condition met with their therapist once each week for a 45-minute video teletherapy session. Self-report data for depression, anxiety, and functional impairment were collected at pretreatment, weekly during treatment, at posttreatment, and at a 6-month follow-up. Self-reported treatment expectancy and credibility for the assigned intervention were assessed at pretreatment and therapeutic alliance at posttreatment.ResultsFindings from multilevel modeling indicated significant, medium-to-large improvements in depression (d=1.04; 95% CI 0.60-1.46), anxiety (d=0.61; 95% CI 0.22-0.99), and functional impairment (d=0.66; 95% CI 0.27-1.05) for patients in the message-based treatment condition. Changes in depression (d=0.11; 95% CI -0.43 to 0.66), anxiety (d=-0.01; 95% CI -0.56 to 0.53), and functional impairment (d=0.25; 95% CI -0.30 to 0.80) in the message-based treatment condition were noninferior to those in the video-based treatment condition. There were no significant differences in treatment credibility (d=-0.09; 95% CI -0.64 to 0.45), therapeutic alliance (d=-0.15; 95% CI -0.75 to 0.44), or engagement (d=0.24; 95% CI -0.20 to 0.67) between the 2 treatment conditions.ConclusionsMessage-based psychotherapy could present an effective and accessible alternative treatment modality for patients who might not be able to engage in traditional scheduled services such as face-to-face or video-based psychotherapy.Trial registrationClinicalTrials.gov NCT05467787; https://www.clinicaltrials.gov/ct2/show/NCT05467787.

Project description:Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example the expression of an aversive behavior upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinctionare only beginning to emerge. Here we show that fear extinction initiates up-regulation of hippocampal insulin-growth factor 2 (Igf2) and down-regulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2-signaling during fear extinction. To this end we show that fear extinction-induced IGF2/IGFBP7-signaling promotes the survival of 17-19 day-old newborn hippocampal neurons. In conclusion, our data suggests that therapeutic strategies that enhance IGF2-signaling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory. We employed mice to investigate fear extinction in the hippocampus-dependent contextual fear conditioning paradigm. To this end, male C57BL/6J mice were exposed to the fear conditioning box (context) followed by an electric foot-shock which elicits the acquisition of conditioned contextual fear. For extinction training animals were repeatedly reexposed to the conditioned context on consecutive days (24h interval) without receiving the footshockagain (extinction trial, E). This procedure eventually results in the decline of the aversive freezing behavior. Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups. To gain a better understanding of the molecular processes underlying fear extinction we performed a genome-wide analysis of the hippocampal transcriptome during fear extinction. In the employed paradigm fear extinction is a gradual process. To capture the longitudinal course of fear extinction we decided to perform hippocampal microarray analysis at two time points: (1) After the first extinction trial (E1) when animals display high levels of aversive freezing behavior and (2) at the extinction trial on which the freezing behavior was significantly reduced when compared to E1. This extinction trial, in the case of this experiment E5, we termed “extinction trial low freezing” (ELF). Mice that were exposed to the conditioning context without receiving fear conditioning training served as control groups (3). For all three groups we hybridized 5 samples (biological replicates).

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Glucocorticoids enhance extinction-based psychotherapy.

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Glucocorticoids enhance extinction-based psychotherapy.

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