A Systematic Review of Fear Learning, Extinction Learning, and Reversal Learning in Obsessive-Compulsive Disorder: Implications for Treatment

References (77)

1. Kessler RC, Chiu WT, Demler O, et al. Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005;62(6):617–627. PubMed CrossRef
2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Fifth Edition. 2013.
3. Koran LM, Thienemann ML, Davenport R. Quality of life for patients with obsessive-compulsive disorder. Am J Psychiatry. 1996;153(6):783–788. PubMed CrossRef
4. Olatunji BO, Davis ML, Powers MB, et al. Cognitive-behavioral therapy for obsessive-compulsive disorder: a meta-analysis of treatment outcome and moderators. J Psychiatr Res. 2013;47(1):33–41. PubMed CrossRef
5. McGuire JF, Piacentini J, Lewin AB, et al. A meta-analysis of cognitive behavior therapy and medication for child obsessive-compulsive disorder: moderators of treatment efficacy, response, and remission: research article: treatment outcomes and moderators in pediatric OCD. Depress Anxiety. 2015;32(8):580–593. PubMed CrossRef
6. Farris SG, McLean CP, Van Meter PE, et al. Treatment response, symptom remission, and wellness in obsessive-compulsive disorder. J Clin Psychiatry. 2013;74(7):685–690. PubMed CrossRef
7. Franklin ME, Sapyta J, Freeman JB, et al. Cognitive behavior therapy augmentation of pharmacotherapy in pediatric obsessive-compulsive disorder: the Pediatric OCD Treatment Study II (POTS II) randomized controlled trial. JAMA. 2011;306(11):1224–1232. PubMed CrossRef
8. Quirk GJ, Mueller D. Neural mechanisms of extinction learning and retrieval. Neuropsychopharmacology. 2008;33(1):56–72. PubMed CrossRef
9. Bouton ME, Westbrook RF, Corcoran KA, et al. Contextual and temporal modulation of extinction: behavioral and biological mechanisms. Biol Psychiatry. 2006;60(4):352–360. PubMed CrossRef
10. Lissek S, Powers AS, McClure EB, et al. Classical fear conditioning in the anxiety disorders: a meta-analysis. Behav Res Ther. 2005;43(11):1391–1424. PubMed CrossRef
11. Blechert J, Michael T, Vriends N, et al. Fear conditioning in posttraumatic stress disorder: evidence for delayed extinction of autonomic, experiential, and behavioural responses. Behav Res Ther. 2007;45(9):2019–2033. PubMed CrossRef
12. Cooper SE, Dunsmoor JE. Fear conditioning and extinction in obsessive-compulsive disorder: a systematic review. Neurosci Biobehav Rev. 2021;129:75–94. PubMed CrossRef
13. McGuire JF, Orr SP, Essoe JKY, et al. Extinction learning in childhood anxiety disorders, obsessive compulsive disorder and post-traumatic stress disorder: implications for treatment. Expert Rev Neurother. 2016;16(10):1155–1174. PubMed CrossRef
14. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2022 statement: a updated guideline for reporting systematic reviews. BMJ. 2021:372n71.
15. The EndNote Team. EndNote. Clarivate; 2013.
16. Nanbu M, Kurayama T, Nakazawa K, et al. Impaired P50 suppression in fear extinction in obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2010;34(2):317–322. PubMed CrossRef
17. Milad MR, Furtak SC, Greenberg JL, et al. Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit. JAMA Psychiatry. 2013;70(6):608–618, quiz 554. PubMed CrossRef
18. McLaughlin NCR, Strong D, Abrantes A, et al. Extinction retention and fear renewal in a lifetime obsessive-compulsive disorder sample. Behav Brain Res. 2015;280:72–77. PubMed CrossRef
19. Giménez M, Cano M, Martínez-Zalacaín I, et al. Is glutamate associated with fear extinction and cognitive behavior therapy outcome in OCD? A pilot study. Eur Arch Psychiatry Clin Neurosci. 2020;270(8):1003–1014. PubMed CrossRef
20. Fyer AJ, Schneier FR, Simpson HB, et al. Heterogeneity in fear processing across and within anxiety, eating, and compulsive disorders. J Affect Disord. 2020;275:329–338. PubMed CrossRef
21. Pöhlchen D, Priouret M, Kraft MS, et al; BeCOME working group. Examining differences in fear learning in patients with obsessive-compulsive disorder with pupillometry, startle electromyography and skin conductance responses. Front Psychiatry. 2021;12:730742. PubMed CrossRef
22. McGuire JF, Orr SP, Wu MS, et al. Fear conditioning and extinction in youth with obsessive-compulsive disorder: fear extinction in youth with OCD. Depress Anxiety. 2016;33(3):229–237. PubMed CrossRef
23. Geller DA, McGuire JF, Orr SP, et al. Fear conditioning and extinction in pediatric obsessive-compulsive disorder. Ann Clin Psychiatry. 2017;29(1):17–26. PubMed
24. Geller DA, McGuire JF, Orr SP, et al. Fear extinction learning as a predictor of response to cognitive behavioral therapy for pediatric obsessive compulsive disorder. J Anxiety Disord. 2019;64:1–8. PubMed CrossRef
25. Apergis-Schoute AM, Gillan CM, Fineberg NA, et al. Neural basis of impaired safety signaling in obsessive compulsive disorder. Proc Natl Acad Sci U S A. 2017;114(12):3216–3221. PubMed CrossRef
26. Elsner B, Reuter B, Said M, et al. Impaired differential learning of fear versus safety signs in obsessive-compulsive disorder. Psychophysiology. 2022;59(2):e13956. CrossRef
27. Pattwell SS, Duhoux S, Hartley CA, et al. Altered fear learning across development in both mouse and human. Proc Natl Acad Sci U S A. 2012;109(40):16318–16323. PubMed CrossRef
28. Shechner T, Hong M, Britton JC, et al. Fear conditioning and extinction across development: evidence from human studies and animal models. Biol Psychol. 2014;100:1–12. PubMed CrossRef
29. Reid JE, Laws KR, Drummond L, et al. Cognitive behavioural therapy with exposure and response prevention in the treatment of obsessive-compulsive disorder: a systematic review and meta-analysis of randomised controlled trials. Compr Psychiatry. 2021;106:152223. PubMed CrossRef
30. Koran LM, Hanna GL, Hollander E, et al; American Psychiatric Association. Practice guideline for the treatment of patients with obsessive-compulsive disorder. Am J Psychiatry. 2007;164(suppl):5–53. PubMed
31. Geller D, March J, The AACAP Committee on Quality Issues. Practice parameter for the assessment and treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(1):98–113. PubMed CrossRef
32. McGuire JF, Storch EA. An inhibitory learning approach to cognitive-behavioral therapy for children and adolescents. Cognit Behav Pract. 2019;26(1):214–224. PubMed CrossRef
33. Craske MG, Treanor M, Conway CC, et al. Maximizing exposure therapy: an inhibitory learning approach. Behav Res Ther. 2014;58:10–23. PubMed CrossRef
34. Arch JJ, Abramowitz JS. Exposure therapy for obsessive–compulsive disorder: an optimizing inhibitory learning approach. J Obsessive Compuls Relat Disord. 2015;6:174–182. CrossRef
35. Blakey SM, Abramowitz JS. The effects of safety behaviors during exposure therapy for anxiety: critical analysis from an inhibitory learning perspective. Clin Psychol Rev. 2016;49:1–15. PubMed CrossRef
36. Dunsmoor JE, Bandettini PA, Knight DC. Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning. Behav Neurosci. 2007;121(4):635–642. PubMed CrossRef
37. Morriss J, Christakou A, van Reekum CM. Nothing is safe: Intolerance of uncertainty is associated with compromised fear extinction learning. Biol Psychol. 2016;121(Pt B):187–193. PubMed CrossRef
38. Morriss J, Saldarini F, van Reekum CM. The role of threat level and intolerance of uncertainty in extinction. Int J Psychophysiol. 2019;142:1–9. PubMed CrossRef
39. Morriss J, Wake S, Elizabeth C, et al. I doubt it is safe: a meta-analysis of self-reported intolerance of uncertainty and threat extinction training. Biol Psychiatry Glob Open Sci. 2021;1(3):171–179. CrossRef
40. Tolin DF, Abramowitz JS, Brigidi BD, et al. Intolerance of uncertainty in obsessive-compulsive disorder. J Anxiety Disord. 2003;17(2):233–242. PubMed CrossRef
41. Gillett CB, Bilek EL, Hanna GL, et al. Intolerance of uncertainty in youth with obsessive-compulsive disorder and generalized anxiety disorder: a transdiagnostic construct with implications for phenomenology and treatment. Clin Psychol Rev. 2018;60:100–108. PubMed CrossRef
42. Holaway RM, Heimberg RG, Coles ME. A comparison of intolerance of uncertainty in analogue obsessive-compulsive disorder and generalized anxiety disorder. J Anxiety Disord. 2006;20(2):158–174. PubMed CrossRef
43. Laposa JM, Collimore KC, Hawley LL, et al. Distress tolerance in OCD and anxiety disorders, and its relationship with anxiety sensitivity and intolerance of uncertainty. J Anxiety Disord. 2015;33:8–14. PubMed CrossRef
44. Carleton RN, Mulvogue MK, Thibodeau MA, et al. Increasingly certain about uncertainty: Intolerance of uncertainty across anxiety and depression. J Anxiety Disord. 2012;26(3):468–479. PubMed CrossRef
45. Shechner T, Rimon-Chakir A, Britton JC, et al. Attention bias modification treatment augmenting effects on cognitive behavioral therapy in children with anxiety: randomized controlled trial. J Am Acad Child Adolesc Psychiatry. 2014;53(1):61–71. PubMed CrossRef
46. Hakamata Y, Lissek S, Bar-Haim Y, et al. Attention bias modification treatment: a meta-analysis toward the establishment of novel treatment for anxiety. Biol Psychiatry. 2010;68(11):982–990. PubMed CrossRef
47. Nasiry S, Ameli Z, Pezeshki P. Research paper: online cognitive bias modification of interpretation for children with obsessive-compulsive disorder. Pract Clin Psychol. 2020;8(4):325–334. CrossRef
48. Najmi S, Amir N. The effect of attention training on a behavioral test of contamination fears in individuals with subclinical obsessive-compulsive symptoms. J Abnorm Psychol. 2010;119(1):136–142. PubMed CrossRef
49. Storch EA, Wilhelm S, Sprich S, et al. Efficacy of augmentation of cognitive behavior therapy with weight-adjusted d -cycloserine vs placebo in pediatric obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry. 2016;73(8):779–788. PubMed CrossRef
50. McGuire JF, Wu MS, Piacentini J, et al. A meta-analysis of D-cycloserine in exposure-based treatment: moderators of treatment efficacy, response, and diagnostic remission. J Clin Psychiatry. 2017;78(2):196–206. PubMed CrossRef
51. Rosenfield D, Smits JAJ, Hofmann SG, et al. Changes in dosing and dose timing of D-cycloserine explain its apparent declining efficacy for augmenting exposure therapy for anxiety-related disorders: an individual participant-data meta-analysis. J Anxiety Disord. 2019;68:102149. PubMed CrossRef
52. Mataix-Cols D, Fernández de la Cruz L, Monzani B, et al; the DCS Anxiety Consortium. 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(5):501–510. PubMed CrossRef
53. McGuire JF, Ginder N, Ramsey K, et al. Optimizing behavior therapy for youth with Tourette’s disorder. Neuropsychopharmacology. 2020;45(12):2114–2119. PubMed CrossRef
54. Roesmann K, Kroker T, Hein S, et al. Transcranial direct current stimulation of the ventromedial prefrontal cortex modulates perceptual and neural patterns of fear generalization. Biol Psychiatry Cogn Neurosci Neuroimaging. 2022;7(2):210–220. PubMed CrossRef
55. Kenwood MM, Kalin NH, Barbas H. The prefrontal cortex, pathological anxiety, and anxiety disorders. Neuropsychopharmacology. 2022;47(1):260–275. PubMed CrossRef
56. Gold AL, Steuber ER, White LK, et al. Cortical thickness and subcortical gray matter volume in pediatric anxiety disorders. Neuropsychopharmacology. 2017;42(12):2423–2433. PubMed CrossRef
57. Shang J, Fu Y, Ren Z, et al. The common traits of the ACC and PFC in anxiety disorders in the DSM-5: meta-analysis of voxel-based morphometry studies. PLoS One. 2014;9(3):e93432. PubMed CrossRef
58. Morriss J, Christakou A, van Reekum CM. Intolerance of uncertainty predicts fear extinction in amygdala-ventromedial prefrontal cortical circuitry. Biol Mood Anxiety Disord. 2015;5(1):4. PubMed CrossRef
59. Fullana MA, Zhu X, Alonso P, et al. Basolateral amygdala-ventromedial prefrontal cortex connectivity predicts cognitive behavioural therapy outcome in adults with obsessive-compulsive disorder. J Psychiatry Neurosci. 2017;42(6):378–385. PubMed CrossRef
60. Marković V, Vicario CM, Yavari F, et al. A systematic review on the effect of transcranial direct current and magnetic stimulation on fear memory and extinction. Front Hum Neurosci. 2021;15:655947. PubMed CrossRef
61. Carmi L, Tendler A, Bystritsky A, et al. Efficacy and safety of deep transcranial magnetic stimulation for obsessive-compulsive disorder: a prospective multicenter randomized double-blind placebo-controlled trial. Am J Psychiatry. 2019;176(11):931–938. PubMed CrossRef
62. Adams TG, Cisler JM, Kelmendi B, et al. Transcranial direct current stimulation targeting the medial prefrontal cortex modulates functional connectivity and enhances safety learning in obsessive-compulsive disorder: results from two pilot studies. Depress Anxiety. 2022;39(1):37–48. PubMed CrossRef
63. Lonsdorf TB, Menz MM, Andreatta M, 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. PubMed CrossRef
64. Morgan CA 3rd, Grillon C, Southwick SM, et al. Fear-potentiated startle in posttraumatic stress disorder. Biol Psychiatry. 1995;38(6):378–385. PubMed CrossRef
65. Davis M. Neural systems involved in fear and anxiety measured with fear-potentiated startle. Am Psychol. 2006;61(8):741–756. PubMed CrossRef
66. Kemp AH, Brunoni AR, Santos IS, et al. Effects of depression, anxiety, comorbidity, and antidepressants on resting-state heart rate and its variability: an ELSA-Brasil cohort baseline study. Am J Psychiatry. 2014;171(12):1328–1334. PubMed CrossRef
67. Ge F, Yuan M, Li Y, et al. Posttraumatic stress disorder and alterations in resting heart rate variability: a systematic review and meta-analysis. Psychiatry Investig. 2020;17(1):9–20. PubMed CrossRef
68. McGuire JF, Lewin AB, Horng B, et al. The nature, assessment, and treatment of obsessive-compulsive disorder. Postgrad Med. 2012;124(1):152–165. PubMed CrossRef
69. Duits P, Cath DC, Lissek S, et al. Updated meta-analysis of fear conditioning in anxiety disorders. Depress Anxiety. 2015;32(4):239–253. PubMed CrossRef
70. Dvir M, Horovitz O, Aderka IM, et al. Fear conditioning and extinction in anxious and non-anxious youth: a meta-analysis. Behav Res Ther. 2019;120:103431. PubMed CrossRef
71. Marin MF, Zsido RG, Song H, et al. Skin conductance responses and neural activations during fear conditioning and extinction recall across anxiety disorders. JAMA Psychiatry. 2017;74(6):622–631. PubMed CrossRef
72. Lewin AB, Wood JJ, Gunderson S, et al. Phenomenology of comorbid autism spectrum and obsessive-compulsive disorders among children. J Dev Phys Disabil. 2011;23(6):543–553. CrossRef
73. Kose LK, Fox L, Storch EA. Effectiveness of cognitive behavioral therapy for individuals with autism spectrum disorders and comorbid obsessive-compulsive disorder: a review of the research. J Dev Phys Disabil. 2018;30(1):69–87. PubMed CrossRef
74. South M, Newton T, Chamberlain PD. Delayed reversal learning and association with repetitive behavior in autism spectrum disorders. Autism Res. 2012;5(6):398–406. PubMed CrossRef
75. South M, Larson MJ, White SE, et al. Better fear conditioning is associated with reduced symptom severity in autism spectrum disorders. Autism Res. 2011;4(6):412–421. PubMed CrossRef
76. Kircanski K, Peris TS. Exposure and response prevention process predicts treatment outcome in youth with OCD. J Abnorm Child Psychol. 2015;43(3):543–552. PubMed CrossRef
77. Kircanski K, Wu M, Piacentini J. Reduction of subjective distress in CBT for childhood OCD: nature of change, predictors, and relation to treatment outcome. J Anxiety Disord. 2014;28(2):125–132. PubMed CrossRef