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Effect of d-cycloserine on fear extinction training in adults with social anxiety disorder


Autoři: Stefan G. Hofmann aff001;  Santiago Papini aff002;  Joseph K. Carpenter aff001;  Michael W. Otto aff001;  David Rosenfield aff003;  Christina D. Dutcher aff002;  Sheila Dowd aff004;  Mara Lewis aff001;  Sara Witcraft aff005;  Mark H. Pollack aff004;  Jasper A. J. Smits aff002
Působiště autorů: Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts, United States of America aff001;  Department of Psychology, University of Texas at Austin, Austin, Texas, United States of America aff002;  Department of Psychology, Southern Methodist University, Dallas, Texas, United States of America aff003;  Department of Psychiatry, Rush University Medical Center, Chicago, Illinois, United States of America aff004;  Department of Psychology, University of Mississippi, Oxford, Mississippi, United States of America aff005
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0223729

Souhrn

Preclinical and clinical data have shown that D-cycloserine (DCS), a partial agonist at the N-methyl-d-aspartate receptor complex, augments the retention of fear extinction in animals and the therapeutic learning from exposure therapy in humans. However, studies with non-clinical human samples in de novo fear conditioning paradigms have demonstrated minimal to no benefit of DCS. The aim of this study was to evaluate the effects of DCS on the retention of extinction learning following de novo fear conditioning in a clinical sample. Eighty-one patients with social anxiety disorder were recruited and underwent a previously validated de novo fear conditioning and extinction paradigm over the course of three days. Of those, only 43 (53%) provided analyzable data. During conditioning on Day 1, participants viewed images of differently colored lamps, two of which were followed by with electric shock (CS+) and a third which was not (CS-). On Day 2, participants were randomly assigned to receive either 50 mg DCS or placebo, administered in a double-blind manner 1 hour prior to extinction training with a single CS+ in a distinct context. Day 3 consisted of tests of extinction recall and renewal. The primary outcome was skin conductance response to conditioned stimuli, and shock expectancy ratings were examined as a secondary outcome. Results showed greater skin conductance and expectancy ratings in response to the CS+ compared to CS- at the end of conditioning. As expected, this difference was no longer present at the end of extinction training, but returned at early recall and renewal phases on Day 3, showing evidence of return of fear. In contrast to hypotheses, DCS had no moderating influence on skin conductance response or expectancy of shock during recall or renewal phases. We did not find evidence of an effect of DCS on the retention of extinction learning in humans in this fear conditioning and extinction paradigm.

Klíčová slova:

Artificial light – Behavioral conditioning – Conditioned response – Fear conditioning – Human learning – Learning – Memory recall – Social anxiety disorder


Zdroje

1. Carpenter JK, Andrews LA, Witcraft SM, Powers MB, Smits JA, Hofmann SG. Cognitive behavioral therapy for anxiety and related disorders: A meta-analysis of randomized placebo-controlled trials. Depress Anxiety. 2018;35: 502–514. doi: 10.1002/da.22728 29451967

2. Hofmann SG, Smits JA. Cognitive-behavioral therapy for adult anxiety disorders: a meta-analysis of randomized placebo-controlled trials. J Clin Psychiatry. 2008;69: 621–632. doi: 10.4088/jcp.v69n0415 18363421

3. Springer KS, Levy HC, Tolin DF. Remission in CBT for adult anxiety disorders: A meta-analysis. Clin Psychol Rev. 2018;61: 1–8. doi: 10.1016/j.cpr.2018.03.002 29576326

4. Taylor S, Abramowitz JS, McKay D. Non-adherence and non-response in the treatment of anxiety disorders. J Anxiety Disord. 2012;26: 583–589. doi: 10.1016/j.janxdis.2012.02.010 22440391

5. Kredlow AM, Eichenbaum H, Otto MW. Memory creation and modification: Enhancing the treatment of psychological disorders. Am Psychol. 2018;73: 269–285. doi: 10.1037/amp0000185 29494172

6. Otto MW, Kredlow MA, Smits JA, Hofmann SG, Tolin DF, de Kleine RA, et al. Enhancement of psychosocial treatment with d-cycloserine: models, moderators, and future directions. Biol Psychiatry. 2016;80: 274–283. doi: 10.1016/j.biopsych.2015.09.007 26520240

7. Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, Eisenmenger K, et al. Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry. 2006;63: 298–304. doi: 10.1001/archpsyc.63.3.298 16520435

8. Hofmann SG, Smits JA, Rosenfield D, Simon N, Otto MW, Meuret AE, et al. D-Cycloserine as an augmentation strategy with cognitive-behavioral therapy for social anxiety disorder. Am J Psychiatry. 2013;170: 751–758. doi: 10.1176/appi.ajp.2013.12070974 23599046

9. Mataix-Cols D, De La Cruz LF, Monzani B, Rosenfield D, Andersson E, Pérez-Vigil A, et al. D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis of individual participant data. JAMA Psychiatry. 2017;74: 501–510. doi: 10.1001/jamapsychiatry.2016.3955 28122091

10. Ledgerwood L, Richardson R, Cranney J. Effects of D-cycloserine on extinction of conditioned freezing. Behav Neurosci. 2003;117: 341–349. doi: 10.1037/0735-7044.117.2.341 12708530

11. Ledgerwood L, Richardson R, Cranney J. D-cycloserine and the facilitation of extinction of conditioned fear: consequences for reinstatement. Behav Neurosci. 2004;118: 505–513. doi: 10.1037/0735-7044.118.3.505 15174928

12. Ledgerwood L, Richardson R, Cranney J. d-cycloserine facilitates extinction of learned fear: Effects on reacquisition and generalized extinction. Biol Psychiatry. 2005;57: 841–847. doi: 10.1016/j.biopsych.2005.01.023 15820704

13. Walker DL, Ressler KJ, Lu K-T, Davis M. Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of d-cycloserine as assessed with fear-potentiated startle in rats. J Neurosci. 2002;22: 2343–2351. doi: 10.1523/JNEUROSCI.22-06-02343.2002 11896173

14. Woods AM, Bouton ME. D-cycloserine facilitates extinction but does not eliminate renewal of the conditioned emotional response. Behav Neurosci. 2006;120: 1159–1162. doi: 10.1037/0735-7044.120.5.1159 17014266

15. Norberg MM, Krystal JH, Tolin DF. A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy. Biol Psychiatry. 2008;63: 1118–1126. doi: 10.1016/j.biopsych.2008.01.012 18313643

16. Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, et al. Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am Psychiatric Assoc; 2010.

17. Klumpers F, Denys D, Kenemans JL, Grillon C, van der Aart J, Baas JM. Testing the effects of Δ9-THC and D-cycloserine on extinction of conditioned fear in humans. J Psychopharmacol (Oxf). 2012;26: 471–478. doi: 10.1177/0269881111431624 22351380

18. Guastella AJ, Lovibond PF, Dadds MR, Mitchell P, Richardson R. A randomized controlled trial of the effect of d-cycloserine on extinction and fear conditioning in humans. Behav Res Ther. 2007;45: 663–672. doi: 10.1016/j.brat.2006.07.005 16962066

19. Kuriyama K, Honma M, Soshi T, Fujii T, Kim Y. Effect of D-cycloserine and valproic acid on the extinction of reinstated fear-conditioned responses and habituation of fear conditioning in healthy humans: a randomized controlled trial. Psychopharmacology (Berl). 2011;218: 589–597. doi: 10.1007/s00213-011-2353-x 21594560

20. Kuriyama K, Honma M, Yoshiike T, Kim Y. Valproic acid but not d-cycloserine facilitates sleep-dependent offline learning of extinction and habituation of conditioned fear in humans. Neuropharmacology. 2013;64: 424–431. doi: 10.1016/j.neuropharm.2012.07.045 22992332

21. Milad MR, Wright CI, Orr SP, Pitman RK, Quirk GJ, Rauch SL. Recall of fear extinction in humans activates the ventromedial prefrontal cortex and hippocampus in concert. Biol Psychiatry. 2007;62: 446–454. doi: 10.1016/j.biopsych.2006.10.011 17217927

22. Milad MR, Pitman RK, Ellis CB, Gold AL, Shin LM, Lasko NB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009;66: 1075–1082. doi: 10.1016/j.biopsych.2009.06.026 19748076

23. Kredlow AM, Orr SP, Otto MW. Who is studied in de novo fear conditioning paradigms? An examination of demographic and stimulus characteristics predicting fear learning. Int J Psychophysiol. 2018;130: 21–28. doi: 10.1016/j.ijpsycho.2018.05.008 29800584

24. Otto MW, Moshier SJ, Kinner DG, Simon NM, Pollack MH, Orr SP. De novo fear conditioning across diagnostic groups in the affective disorders: evidence for learning impairments. Behav Ther. 2014;45: 619–629. doi: 10.1016/j.beth.2013.12.012 25022773

25. Marin MF, Barbey F, Rosenbaum BL, Hammoud MZ, Orr SP, Milad MR. Absence of conditioned responding in humans: A bad measure or individual differences?. Psychophysiol. 2019;13: e13350. doi: 10.1111/psyp.13350 30758048

26. Hofmann SG, Carpenter JK, Otto MW, Rosenfield D, Smits JAJ, Pollack MH. Dose timing of d-cycloserine to augment cognitive behavioral therapy for social anxiety: study design and rationale. Contemp Clin Trials. 2015;43: 223–230. doi: 10.1016/j.cct.2015.06.015 26111923

27. Lonsdorf TB, Menz MM, Andreatta M, Fullana MA, Golkar A, Haaker J, et al. Don’t fear ‘fear conditioning’: Methodological considerations for the design and analysis of studies on human fear acquisition, extinction, and return of fear. Neurosci Biobehav Rev. 2017;77: 247–285. doi: 10.1016/j.neubiorev.2017.02.026 28263758

28. Lonsdorf TB, Merz CJ, Fullana MA. Fear extinction retention: is it what we think it is? Biol Psychiatry. 2019;85: 1074–1082. doi: 10.1016/j.biopsych.2019.02.011 31005240

29. Liebowitz MR. Social phobia. Mod Probl Pharmacopsychiatry. 1987;22: 141–173. doi: 10.1159/000414022 2885745

30. Montgomery SA, Åsberg M. A New depression scale designed to be sensitive to change. br j psychiatry. 1979;134: 382–389. doi: 10.1192/bjp.134.4.382 444788

31. Grady AK, Bowen KH, Hyde AT, Totsch SK, Knight DC. Effect of continuous and partial reinforcement on the acquisition and extinction of human conditioned fear. Behav Neurosci. 2016;130: 36–43. doi: 10.1037/bne0000121 26692449

32. Benedek M, Kaernbach C. A continuous measure of phasic electrodermal activity. J Neurosci Methods. 2010;190: 80–91. doi: 10.1016/j.jneumeth.2010.04.028 20451556

33. Fricchione J, Greenberg MS, Spring J, Wood N, Mueller‐Pfeiffer C, Milad MR, et al. Delayed extinction fails to reduce skin conductance reactivity to fear-conditioned stimuli. Psychophysiology. 2016;53: 1343–1351. doi: 10.1111/psyp.12687 27314560

34. Kredlow AM, Orr SP, Otto MW. Exploring the boundaries of post-retrieval extinction in healthy and anxious individuals. Behav Res Ther. 2018;108: 45–57. doi: 10.1016/j.brat.2018.06.010 29981938

35. Schiller D, Kanen JW, LeDoux JE, Monfils M-H, Phelps EA. Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement. Proc Natl Acad Sci. 2013;110: 20040–20045. doi: 10.1073/pnas.1320322110 24277809

36. Steinfurth ECK, Kanen JW, Raio CM, Clem RL, Huganir RL, Phelps EA. Young and old Pavlovian fear memories can be modified with extinction training during reconsolidation in humans. Learn Mem. 2014;21: 338–341. doi: 10.1101/lm.033589.113 24934333

37. Duits P, Cath DC, Lissek S, Hox JJ, Hamm AO, Engelhard IM, et al. Updated meta‐analysis of classical fear conditioning in the anxiety disorders. Depress Anxiety. 2015;32: 239–253. doi: 10.1002/da.22353 25703487

38. Kredlow AM, Unger LD, Otto MW. Harnessing reconsolidation to weaken fear and appetitive memories: a meta-analysis of post-retrieval extinction effects. Psychol Bull. 2016;142: 314–336. doi: 10.1037/bul0000034 26689086

39. Grillon C. DCS facilitation of fear extinction and exposure-based therapy may rely on lower-level, automatic mechanisms. Biol Psychiatry. 2009;66: 636–641. doi: 10.1016/j.biopsych.2009.04.017 19520359

40. Carpenter JK, Pinaire M, Hofmann SG. from extinction learning to anxiety treatment: Mind the gap. Brain Sci. 2019;9: 164.

41. Mineka S, Öhman A. Phobias and preparedness: The selective, automatic, and encapsulated nature of fear. Biol Psychiatry. 2002;52: 927–937. doi: 10.1016/s0006-3223(02)01669-4 12437934

42. Mallan KM, Lipp OV, Cochrane B. Slithering snakes, angry men and out-group members: What and whom are we evolved to fear?. Cogn Emot. 2013;27: 1168–1180. doi: 10.1080/02699931.2013.778195 23556423


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