Reconsolidation-based treatment for fear of public speaking: a systematic pilot study using propranolol.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
received:
14
10
2019
accepted:
14
05
2020
revised:
23
03
2020
entrez:
6
6
2020
pubmed:
6
6
2020
medline:
22
6
2021
Statut:
epublish
Résumé
Pharmacological manipulation of memory reconsolidation opens up promising new avenues for anxiety disorder treatment. However, few studies have directly investigated reconsolidation-based approaches in subclinical or clinical populations, leaving optimal means of fear memory reactivation unknown. We conducted a systematic pilot study to assess whether a reconsolidation-based treatment could tackle public speaking anxiety in a subclinical sample (N = 60). As lab studies indicate that the duration of reactivation may be important for inducing reconsolidation, we investigated several speech lengths to help inform further translational efforts. Participants underwent a stress-inducing speech task composed of 3-min preparation, and from 0 to 9 min of public speaking, in 1-min increments. They then received either 40 mg of propranolol (n = 40) or placebo (n = 20), double-blind, allocated 4:2 for each speech duration. Participants performed a second speech 1 week post treatment, and were followed up with questionnaires 1- and 3 months later. Both self-reported speech distress and questionnaire measures of public speaking anxiety showed clear reductions following treatment. However, propranolol did not reliably outperform placebo, regardless of speech duration at treatment. Physiological responses (heart rate and salivary cortisol) to the public speaking task remained stable from treatment to test. These findings highlight the challenges facing the translation of laboratory research on memory reconsolidation into clinical interventions. Lack of explicit controls for factors beyond duration, such as 'prediction error', could explain these null findings, but positive results in clinical interventions are needed to demonstrate that taking such factors into account can deliver the promises of reconsolidation-based therapy.
Identifiants
pubmed: 32499503
doi: 10.1038/s41398-020-0857-z
pii: 10.1038/s41398-020-0857-z
pmc: PMC7272450
doi:
Substances chimiques
Adrenergic beta-Antagonists
0
Propranolol
9Y8NXQ24VQ
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
179Références
LeDoux, J., Romanski, L. & Xagoraris, A. Indelibility of subcortical emotional memories. J. Cogn. Neurosci. 1, 238–243, https://doi.org/10.1162/jocn.1989.1.3.238 (1989).
doi: 10.1162/jocn.1989.1.3.238
Przybyslawski, J., Roullet, P. & Sara, S. J. Attenuation of emotional and nonemotional memories after their reactivation: Role of β adrenergic receptors. J. Neurosci. 19, 6623–6628 (1999).
doi: 10.1523/JNEUROSCI.19-15-06623.1999
Przybyslawski, J. & Sara, S. J. Reconsolidation of memory after its reactivation. Behav. Brain Res. 84, 241–246 (1997).
doi: 10.1016/S0166-4328(96)00153-2
LeDoux, J. E., Nader, K. & Schafe, G. E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722–726, https://www.nature.com/articles/35021052 (2000).
Elsey, J. W. B., Van Ast, V. A. & Kindt, M. Human memory reconsolidation: a guiding framework and critical review of the evidence. Psychol. Bull. 144, 797–848 (2018).
doi: 10.1037/bul0000152
Nader, K. & Hardt, O. A single standard for memory: the case for reconsolidation. Nat. Rev. Neurosci. [Internet]. 10, 224–234 (2009).
doi: 10.1038/nrn2590
Spear, N. Extending the domain of memory retrieval. in Information Processing in Animals: Memory Mechanisms (eds. Spear, N. E. & Miller, R. R.) 341–378 (Lawrence Erlbaum Associates, Hillsdale, NJ, 1981).
Riccio, D. C., Millin, P. M. & Bogart, A. R. Reconsolidation: a brief history, a retrieval view, and some recent issues [Internet]. Learn. Memory 13, 536–544 (2006).
Elsey, J. W. B. & Kindt, M. Tackling maladaptive memories through reconsolidation: from neural to clinical science. Neurobiol. Learn Mem. 142, 108–117 (2017).
doi: 10.1016/j.nlm.2017.03.007
Nader, K., Hardt, O. & Lanius, R. Memory as a new therapeutic target. Dialogues Clin. Neurosci. 15, 475–486 (2013).
doi: 10.31887/DCNS.2013.15.4/knader
Kindt, M. The surprising subtleties of changing fear memory: a challenge for translational science. Philos. Trans. R. Soc. B Biol. Sci. 373, 20170033 (2018).
doi: 10.1098/rstb.2017.0033
Telch, M. J., York, J., Lancaster, C. L. & Monfils, M. H. Use of a brief fear memory reactivation procedure for enhancing exposure therapy. Clin. Psychol. Sci. 5, 367–378 (2017).
doi: 10.1177/2167702617690151
Maples-Keller, J. L. et al. Targeting memory reconsolidation to prevent the return of fear in patients with fear of flying. Depress Anxiety 34, 610–620 (2017).
doi: 10.1002/da.22626
Dębiec, J. & Ledoux, J. E. Disruption of reconsolidation but not consolidation of auditory fear conditioning cy noradrenergic blockade in the amygdala. Neuroscience 129, 267–272 (2004).
doi: 10.1016/j.neuroscience.2004.08.018
Kandel, E. The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038 (2001).
doi: 10.1126/science.1067020
Tully, K. & Bolshakov, V. Y. Emotional enhancement of memory: how norepinephrine enables synaptic plasticity. Mol. Brain 3, 15 (2010).
doi: 10.1186/1756-6606-3-15
Kindt, M., Soeter, M. & Vervliet, B. Beyond extinction: erasing human fear responses and preventing the return of fear. Nat. Neurosci. 12, 256–258 (2009).
doi: 10.1038/nn.2271
Kindt, M. & Soeter, M. Pharmacologically induced amnesia for learned fear is time and sleep dependent. Nat. Commun. 9, 1316 (2018).
doi: 10.1038/s41467-018-03659-1
Bos, M. G. N., Beckers, T. & Kindt, M. Noradrenergic blockade of memory reconsolidation: a failure to reduce conditioned fear responding. Front. Behav. Neurosci. 8, 412 (2014).
doi: 10.3389/fnbeh.2014.00412
Schroyens, N., Beckers, T. & Kindt, M. In search for boundary conditions of reconsolidation: a failure of fear memory interference. Front Behav. Neurosci. 11, 65 (2017).
doi: 10.3389/fnbeh.2017.00065
Poundja, J., Sanche, S., Tremblay, J. & Brunet, A. Trauma reactivation under the influence of propranolol: an examination of clinical predictors. Eur. J. Psychotraumatol. 3, 15470 (2012).
doi: 10.3402/ejpt.v3i0.15470
Brunet, A. et al. Reduction of PTSD symptoms with pre-reactivation propranolol therapy: a randomized controlled trial. Am. J. Psychiatry. 175, 427–433 (2018).
doi: 10.1176/appi.ajp.2017.17050481
Kindt, M. & van Emmerik, A. New avenues for treating emotional memory disorders: towards a reconsolidation intervention for posttraumatic stress disorder. Ther. Adv. Psychopharmacol. 6, 283–295 (2016).
doi: 10.1177/2045125316644541
Wood, N. E. et al. Pharmacological blockade of memory reconsolidation in posttraumatic stress disorder: three negative psychophysiological studies. Psychiatry Res. 225, 31–39 (2015).
doi: 10.1016/j.psychres.2014.09.005
Soeter, M. & Kindt, M. An abrupt transformation of phobic behavior following a post-retrieval amnesic agent. Biol. Psychiatry 78, 880–886 (2015).
doi: 10.1016/j.biopsych.2015.04.006
Elsey, J. W. B. & Kindt, M. Breaking boundaries: optimizing reconsolidation-based interventions for strong and old memories. Learn Mem. 24, 472–479 (2017).
doi: 10.1101/lm.044156.116
American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®) [Internet]. https://books.google.nl/books?hl=en&lr=&id=-JivBAAAQBAJ&oi=fnd&pg=PT18&dq=dsm+v&ots=ceSR37LIBf&sig=Obkth-L_onUr4qZR926A8kED33Y (2013).
Blöte, A., Kint, M., Miers, A. & Westenberg, P. The relation between public speaking anxiety and social anxiety: a review. J. Anxiety Disord. 23, 305–313 (2009).
doi: 10.1016/j.janxdis.2008.11.007
Bögels, S. M. et al. Social anxiety disorder: questions and answers for the DSM-V. Depress Anxiety 27, 168–189 (2010).
doi: 10.1002/da.20670
Heimberg, R. G. et al. Social anxiety disorder in DSM-5. Depress Anxiety 31, 472–479 (2014).
doi: 10.1002/da.22231
Bodie, G. D. A racing heart, rattling knees, and ruminative thoughts: defining, explaining, and treating public speaking anxiety. Commun. Educ. 59, 70–105 (2010).
doi: 10.1080/03634520903443849
Fernández, R., Boccia, M. & Pedreira, M. The fate of memory: reconsolidation and the case of prediction error. Neurosci. Biobehav Rev. 68, 423–441 (2016).
doi: 10.1016/j.neubiorev.2016.06.004
Sevenster, D., Beckers, T. & Kindt, M. Retrieval per se is not sufficient to trigger reconsolidation of human fear memory. Neurobiol. Learn Mem. 97, 338–345 (2012).
doi: 10.1016/j.nlm.2012.01.009
Sevenster, D., Beckers, T. & Kindt, M. Prediction error governs pharmacologically induced amnesia for learned fear. Science 339, 830–833 (2013).
doi: 10.1126/science.1231357
Merlo, E., Milton, A., Goozée, Z., Theobald, D. & Everitt, B. Reconsolidation and extinction are dissociable and mutually exclusive processes: behavioral and molecular evidence. J. Neurosci. 34, 2422–2431 (2014).
doi: 10.1523/JNEUROSCI.4001-13.2014
Sevenster, D., Beckers, T. & Kindt, M. Prediction error demarcates the transition from retrieval, to reconsolidation, to new learning. Learn Mem. 21, 580–584 (2014).
doi: 10.1101/lm.035493.114
Alfei, J., Monti, R., Molina, V., Bueno, A. & Urcelay, G. Prediction error and trace dominance determine the fate of fear memories after post-training manipulations. Learn Mem. 22, 385–400 (2015).
doi: 10.1101/lm.038513.115
Cassini, L., Flavell, C., Amaral, O. & Lee, J. On the transition from reconsolidation to extinction of contextual fear memories. Learn Mem. 24, 392–399 (2017).
doi: 10.1101/lm.045724.117
Kirschbaum, C., Pirke, K. & Hellhammer, D. The “Trier Social Stress Test”—a tool for investigating psychobiological stress responses in a laboratory setting. Psychopharmacology 28, 76–81 (1993).
Vehtari, A., Gelman, A. & Gabry, J. Practical Bayesian model evaluation using leave-one-out cross-validation and WAIC. Stat. Comput. 27, 1413–1432 (2017).
doi: 10.1007/s11222-016-9696-4
Clark, D. & Wells, A. A cognitive model of social phobia. in Social Phobia: Diagnosis, Assessment, and Treatment (eds Liebowitz, M., Heimberg, R. G.) 1st edn., 69–93 (Guilford Press, NY, 1995).
Vassilopoulos, S. P. Anticipatory processing plays a role in maintaining social anxiety. Anxiety, Stress Coping 18, 321–332 (2005).
doi: 10.1080/10615800500258149
Soeter, M. & Kindt, M. High trait anxiety: a challenge for disrupting fear memory reconsolidation. PLoS ONE 8, e75239 (2013).
doi: 10.1371/journal.pone.0075239
Casagrande, M. et al. Synaptic consolidation as a temporally variable process: uncovering the parameters modulating its time-course. Neurobiol. Learn Mem. 150, 42–47 (2018).
doi: 10.1016/j.nlm.2018.03.002
Das, R. K. et al. Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories. Nat. Commun. 10, 1–10 (2019).
doi: 10.1038/s41467-019-13162-w
Kroenke, K., Spitzer, R. L. & Williams, J. B. W. The PHQ-9: validity of a brief depression severity measure. J. Gen. Intern Med. 16, 606–613 (2001).
doi: 10.1046/j.1525-1497.2001.016009606.x
McCroskey, J. C. Measures of communication‐bound anxiety. Speech Monogr. 37, 269–277 (1970).
doi: 10.1080/03637757009375677
Niles, A., Craske, M., Lieberman, M. & Hur, C. Affect labeling enhances exposure effectiveness for public speaking anxiety. Behav. Res Ther. 60, 27–35 (2015).
doi: 10.1016/j.brat.2015.03.004
Wolpe, J. & Lazarus, A. Behavior Therapy Techniques: A Guide to the Treatment of Neuroses (Pergamon, NY, 1966).
Rapee, R. & Lim, L. Discrepancy between self-and observer ratings of performance in social phobics. J. Abnorm Psychol. 101, 728–731 (1992).
doi: 10.1037/0021-843X.101.4.728
Baker, S., Heinrichs, N., Kim, H. & Hofmann, S. G. The Liebowitz social anxiety scale as a self-report instrument: a preliminary psychometric analysis. Behav. Res Ther. 40, 701–715 (2002).
doi: 10.1016/S0005-7967(01)00060-2
Heimberg, R. G. et al. Psychometric properties of the Liebowitz social anxiety scale. Psychol. Med. 29, 199–212 (1999).
doi: 10.1017/S0033291798007879
Fresco, D. et al. The Liebowitz Social Anxiety Scale: a comparison of the psychometric properties of self-report and clinician-administered formats. Psychol. Med. 31, 1025–1035 (2001).
doi: 10.1017/S0033291701004056
Clark, D. M. et al. Cognitive therapy versus fluoxetine in generalized social phobia: a randomized placebo-controlled trial. J. Consult Clin. Psychol. 71, 1058–1067 (2003).
doi: 10.1037/0022-006X.71.6.1058
Reiss, S., Peterson, R., Gursky, D. & McNally, R. Anxiety sensitivity, anxiety frequency and the prediction of fearfulness. Behav. Res. Ther. 24, 1–8 (1986).
doi: 10.1016/0005-7967(86)90143-9
Rosenberg, M. Society and the Adolescent Self-Image (Princeton University Press, Princeton, NJ, 1965).
doi: 10.1515/9781400876136
Spielberger, C., Gorsuch, R. & Lusthene, R. Manual for the State-Trait Anxiety Inventory (Consulting Psychologists, Palo Alto, 1970).
Altini, M. Heart rate variability logger. [Smartphone app]. (2013).
Plews, D. J. et al. Comparison of heart-rate-variability recording with smartphone photoplethysmography, polar H7 chest strap, and electrocardiography. Int. J. Sports Physiol. Perform. 12, 1324–1328 (2017).
doi: 10.1123/ijspp.2016-0668
Goodman, L. S. Goodman and Gilman’s the Pharmacological Basis of Therapeutics, Vol. 1549 (McGraw-Hill, NY, 1996).
Bürkner, P.-C. brms: An R package for Bayesian multilevel models using Stan. J. Stat. Softw. 80, 1–28 (2017).
doi: 10.18637/jss.v080.i01
JASP Team. JASP (Version 0.12.2) [Computer software]. (2020).
Vehtari, A., Gabry, J., Magnusson, M., Yao, Y., & Gelman, A. loo: efficient leave-one-out cross-validation and WAIC for Bayesian models. R package version 2.2.0, https://mc-stan.org/loo (2019).
Wagenmakers, E.-J. et al. Bayesian inference for psychology. Part II: example applications with JASP. Psychon. Bull. Rev. 25, 58–76 (2018).
doi: 10.3758/s13423-017-1323-7