Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder

Molecular Psychiatry volume 26, pages 6952–6962 (2021)Cite this article

Subjects

Abstract

It is of great clinical importance to explore more efficacious treatments for OCD. Recently, cognitive-coping therapy (CCT), mainly focusing on recognizing and coping with a fear of negative events, has been reported as an efficacious psychotherapy. However, the underlying neurophysiological mechanism remains unknown. This study of 79 OCD patients collected Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after four weeks of CCT, pharmacotherapy plus CCT (pCCT), or pharmacotherapy. Amygdala seed-based functional connectivity (FC) analysis was performed. Compared post- to pretreatment, pCCT-treated patients showed decreased left amygdala (LA) FC with the right anterior cingulate gyrus (cluster 1) and with the left paracentral lobule/the parietal lobe (cluster 2), while CCT-treated patients showed decreased LA-FC with the left middle occipital gyrus/the left superior parietal/left inferior parietal (cluster 3). The z-values of LA-FC with the three clusters were significantly lower after pCCT or CCT than pretreatment in comparisons of covert vs. overt and of non-remission vs. remission patients, except the z-value of cluster 2 in covert OCD. CCT and pCCT significantly reduced the Y-BOCS score. The reduction in the Y-BOCS score was positively correlated with the z-value of cluster 1. Our findings demonstrate that both pCCT and CCT with large effect sizes lowered LA-FC, indicating that FCs were involved in OCD. Additionally, decreased LA-FC with the anterior cingulate cortex (ACC) or paracentral/parietal cortex may be a marker for pCCT response or a marker for distinguishing OCD subtypes. Decreased LA-FC with the parietal region may be a common pathway of pCCT and CCT. Trial registration: ChiCTR-IPC-15005969.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2: Alterations in amygdala seed-based functional connectivity in patients with OCD who received pCCT.
Fig. 3: Alterations in amygdala seed-based functional connectivity in patients with OCD who received CCT.
Fig. 4: Correlation of Y-BOCS improvement and alteration of FC with cluster 1 in patients with pCCT.

Similar content being viewed by others

References

  1. Holes RE, Yudofsky SC, Roberts LW. Textbook of psychiatry. Arlington, VA: The American Psychiatric Publishing; 2014.

  2. Huang Y, Wang Y, Wang H, Liu Z, Yu X, Yan J, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry. 2019;6:211–24.

    Article  PubMed  Google Scholar 

  3. Maia TV, Cooney RE, Peterson BS. The neural bases of obsessive-compulsive disorder in children and adults. Dev Psychopathol. 2008;20:1251–83.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Marsh R, Horga G, Parashar N, Wang Z, Peterson BS, Simpson HB. Altered activation in fronto-striatal circuits during sequential processing of conflict in unmedicated adults with obsessive-compulsive disorder. Biol Psychiatry. 2014;75:615–22.

    Article  PubMed  Google Scholar 

  5. Paul S, Beucke JC, Kaufmann C, Mersov A, Heinzel S, Kathmann N, et al. Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder. Psychol Med. 2019;49:278–86.

    Article  PubMed  Google Scholar 

  6. Viol K, Aas B, Kastinger A, Kronbichler M, Schöller H, Reiter EM, et al. Individual OCD-provoking stimuli activate disorder-related and self-related neuronal networks in fMRI. Psychiatry Res Neuroimaging. 2019;283:135–44.

    Article  PubMed  Google Scholar 

  7. Kuhn S, Kaufmann C, Simon D, Endrass T, Gallinat J, Kathmann N. Reduced thickness of anterior cingulate cortex in obsessive-compulsive disorder. Cortex. 2013;49:2178–85.

    Article  PubMed  Google Scholar 

  8. Stern ER, Fitzgerald KD, Welsh RC, Abelson JL, Taylor SF. Resting-state functional connectivity between fronto-parietal and default mode networks in obsessive-compulsive disorder. PLoS ONE. 2012;7:3.

    Article  Google Scholar 

  9. Jaspers-Fayer F, Lin SY, Chan E, Ellwyn R, Lim R, Best J, et al. Neural correlates of symptom provocation in pediatric obsessive-compulsive disorder. NeuroImage Clin. 2019;24:102034.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Boedhoe PS, Schmaal L, Abe Y, Ameis SH, Arnold PD, Batistuzzo MC, et al. Distinct subcortical volume alterations in pediatric and adult OCD: a worldwide meta- and mega-analysis. Am J Psychiatry. 2017;174:60–9.

    Article  PubMed  Google Scholar 

  11. Viol K, Aas B, Kastinger A, Kronbichler M, Schöller HJ, Reiter EM, et al. Erroneously disgusted: fMRI study supports disgust-related neural reuse in obsessive-compulsive disorder (OCD). Front Behav Neurosci. 2019;13:81.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Eng GK, Sim K, Chen S-HA. Meta-analytic investigations of structural grey matter, executive domain-related functional activations, and white matter diffusivity in obsessive compulsive disorder: an integrative review. Neurosci Biobehav Rev. 2015;52:233–57.

    Article  PubMed  Google Scholar 

  13. Hollander E, Bienstock CA, Koran LM, Pallanti S, Marazziti D, Rasmussen SA, et al. Refractory obsessive-compulsive disorder: state-of-the-art treatment. J Clin Psychiatry. 2002;63 Suppl 6:20–9.

    PubMed  Google Scholar 

  14. Otte C. Cognitive behavioral therapy in anxiety disorders: current state of the evidence. Dialogues Clin Neurosci. 2011;13:413–21.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Saxena S, Gorbis E, O’Neill J, Baker SK, Mandelkern MA, Maidment KM, et al. Rapid effects of brief intensive cognitive-behavioral therapy on brain glucose metabolism in obsessive-compulsive disorder. Mol Psychiatry. 2009;14:197–205.

    Article  CAS  PubMed  Google Scholar 

  16. Baxter LR Jr., Schwartz JM, Bergman KS, Szuba MP, Guze BH, Mazziotta JC, et al. Caudate glucose metabolic rate changes with both drug and behavior therapy for obsessive-compulsive disorder. Arch Gen Psychiatry. 1992;49:681–9.

    Article  CAS  PubMed  Google Scholar 

  17. Li P, Yang X, Greenshaw AJ, Li S, Luo J, Han H, et al. The effects of cognitive behavioral therapy on resting-state functional brain network in drug-naive patients with obsessive-compulsive disorder. Brain Behav. 2018;8:e00963.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moody TD, Morfini F, Cheng G, Sheen C, Tadayonnejad R, Reggente N, et al. Mechanisms of cognitive-behavioral therapy for obsessive-compulsive disorder involve robust and extensive increases in brain network connectivity. Transl Psychiatry. 2017;7:e1230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Feusner JD, Moody T, Lai TM, Sheen C, Khalsa S, Brown J, et al. Brain connectivity and prediction of relapse after cognitive-behavioral therapy in obsessive-compulsive disorder. Front Psychiatry. 2015;6:74.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Reggente N, Moody TD, Morfini F, Sheen C, Rissman J, O’Neill J, et al. Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder. Proc Natl Acad Sci USA. 2018;115:2222–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ma JD, Wang CH, Li HF, Zhang XL, Zhang YL, Hou YH, et al. Cognitive-coping therapy for obsessive-compulsive disorder: a randomized controlled trial. J Psychiatr Res. 2013;47:1785–90.

    Article  PubMed  Google Scholar 

  22. Hu X-Z. A novel cognitive-coping therapy for obsessive-complusive disorder. J Appl Clin Pediatr. 2010;25:1848–51.

    Google Scholar 

  23. Hu X-Z, Ma J-D. Clinical effect of pharmacotherapy combined with cognitive-coping therapy on obsessive-compulsive disorder. J Xinxiang Med Coll. 2011;28:68–72.

    Google Scholar 

  24. Hu XZ, Wen YS, Ma JD, Han DM, Li YX, Wang SF. A promising randomized trial of a new therapy for obsessive-compulsive disorder. Brain Behav. 2012;2:443–54.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Hu XZ, Ma JD, Huang P, Shan XW, Zhang ZH, Zhang JH, et al. Highly efficacious cognitive-coping therapy for overt or covert compulsions. Psychiatry Res. 2015;229:732–8.

    Article  PubMed  Google Scholar 

  26. Sang DE, Shi LJ, Yue KC, He CY, Zhao HZ, Wang CH, et al. Clinical remission of a treatment-refractory individual with severe repetitive rituals and rumination. Asian J Psychiatr. 2020;47:101878.

    Article  PubMed  Google Scholar 

  27. Ji G, Wei W, Yue K-C, Li H, Shi L-J, Ma J-D, et al. Effects of the COVID-19 pandemic on obsessive-compulsive symptoms among university students: prospective cohort survey study. J Med Internet Res. 2020;22:e21915.

  28. Szeszko PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J, et al. Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings. Neuropsychopharmacology. 2004;29:826–32.

    Article  CAS  PubMed  Google Scholar 

  29. Viard A, Flament MF, Artiges E, Dehaene S, Naccache L, Cohen D, et al. Cognitive control in childhood-onset obsessive-compulsive disorder: a functional MRI study. Psychol Med. 2005;35:1007–17.

    Article  PubMed  Google Scholar 

  30. Milad MR, Rauch SL. Obsessive-compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci. 2012;16:43–51.

    Article  PubMed  Google Scholar 

  31. van Velzen LS, de Wit SJ, Ćurĉić-Blake B, Cath DC, de Vries FE, Veltman DJ, et al. Altered inhibition-related frontolimbic connectivity in obsessive-compulsive disorder. Hum Brain Mapp. 2015;36:4064–75.

    Article  PubMed  PubMed Central  Google Scholar 

  32. de Vries FE, de Wit SJ, Cath DC, van der Werf YD, van der Borden V, van Rossum TB, et al. Compensatory frontoparietal activity during working memory: an endophenotype of obsessive-compulsive disorder. Biol Psychiatry. 2014;76:878–87.

    Article  PubMed  Google Scholar 

  33. Göttlich M, Krämer UM, Kordon A, Hohagen F, Zurowski B. Resting-state connectivity of the amygdala predicts response to cognitive behavioral therapy in obsessive compulsive disorder. Biol Psychol. 2015;111:100–9.

    Article  PubMed  Google Scholar 

  34. Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, et al. Dose equivalents of antidepressants: Evidence-based recommendations from randomized controlled trials. J Affect Disord. 2015;180:179–84.

    Article  CAS  PubMed  Google Scholar 

  35. Yan C-G, Zang Y-F. DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI. Front Syst Neurosci. 2010;4:13.

    Google Scholar 

  36. Power JD, Barnes KA, Snyder AZ, Schlaggar BL, Petersen SE. Steps toward optimizing motion artifact removal in functional connectivity MRI; a reply to Carp. NeuroImage. 2013;76:439–41.

    Article  PubMed  Google Scholar 

  37. Thorsen AL, Hagland P, Radua J, Mataix-Cols D, Kvale G, Hansen B, et al. Emotional processing in obsessive-compulsive disorder: a systematic review and meta-analysis of 25 functional neuroimaging studies. Biol Psychiatry Cogn Neurosci Neuroimaging. 2018;3:563–71.

    PubMed  PubMed Central  Google Scholar 

  38. Zikopoulos B, Höistad M, John Y, Barbas H. Posterior orbitofrontal and anterior cingulate pathways to the amygdala target inhibitory and excitatory systems with opposite functions. J Neurosci. 2017;37:5051–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Adler CM, McDonough-Ryan P, Sax KW, Holland SK, Arndt S, Strakowski SM. fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder. J Psychiatr Res. 2000;34:317–24.

    Article  CAS  PubMed  Google Scholar 

  40. Perani D, Colombo C, Bressi S, Bonfanti A, Grassi F, Scarone S, et al. [18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment. Br J Psychiatry. 1995;166:244–50.

    Article  CAS  PubMed  Google Scholar 

  41. Lustberg D, Iannitelli AF, Tillage RP, Pruitt M, Liles LC, Weinshenker D. Central norepinephrine transmission is required for stress-induced repetitive behavior in two rodent models of obsessive-compulsive disorder. Psychopharmacology. 2020;237:1973–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Senova S, Clair A-H, Palfi S, Yelnik J, Domenech P, Mallet L. Deep brain stimulation for refractory obsessive-compulsive disorder: towards an individualized approach. Front Psychiatry. 2019;10:905.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Bjorgvinsson T, Hart J, Heffelfinger S. Obsessive-compulsive disorder: update on assessment and treatment. J Psychiatr Pract. 2007;13:362–72.

    Article  PubMed  Google Scholar 

  44. O’Neill J, Gorbis E, Feusner JD, Yip JC, Chang S, Maidment KM, et al. Effects of intensive cognitive-behavioral therapy on cingulate neurochemistry in obsessive-compulsive disorder. J Psychiatr Res. 2013;47:494–504.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Rus OG, Reess TJ, Wagner G, Zimmer C, Zaudig M, Koch K. Functional and structural connectivity of the amygdala in obsessive-compulsive disorder. NeuroImage Clin. 2017;13:246–55.

    Article  PubMed  Google Scholar 

  46. Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525–49.

    Article  PubMed  Google Scholar 

  47. Nordahl TE, Benkelfat C, Semple WE, Gross M, King AC, Cohen RM. Cerebral glucose metabolic rates in obsessive compulsive disorder. Neuropsychopharmacology. 1989;2:23–8.

    Article  CAS  PubMed  Google Scholar 

  48. Kwon JS, Kim JJ, Lee DW, Lee JS, Lee DS, Kim MS, et al. Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder. Psychiatry Res. 2003;122:37–47.

    Article  PubMed  Google Scholar 

  49. Goncalves OF, Marques TR, Lori NF, Sampaio A, Branco MC. Obsessive-compulsive disorder as a visual processing impairment. Med Hypotheses. 2010;74:107–9.

    Article  PubMed  Google Scholar 

  50. Gonçalves ÓF, Carvalho S, Leite J, Fernandes-Gonçalves A, Carracedo A, Sampaio A. Cognitive and emotional impairments in obsessive-compulsive disorder: evidence from functional brain alterations. Porto Biomed J. 2016;1:92–105.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Tadayonnejad R, Deshpande R, Ajilore O, Moody T, Morfini F, Ly R, et al. Pregenual anterior cingulate dysfunction associated with depression in OCD: an integrated multimodal fMRI/(1)H MRS study. Neuropsychopharmacology. 2018;43:1146–55.

    Article  CAS  PubMed  Google Scholar 

  52. Cardoner N, Soriano-Mas C, Pujol J, Alonso P, Harrison BJ, Deus J, et al. Brain structural correlates of depressive comorbidity in obsessive-compulsive disorder. NeuroImage. 2007;38:413–21.

    Article  PubMed  Google Scholar 

  53. Kong XZ, Boedhoe PSW, Abe Y, Alonso P, Ameis SH, Arnold PD, et al. Mapping cortical and subcortical asymmetry in obsessive-compulsive disorder: findings from the ENIGMA consortium. Biol Psychiatry. 2020;87:1022–34.

    Article  PubMed  Google Scholar 

  54. Remijnse PL, van den Heuvel OA, Nielen MM, Vriend C, Hendriks GJ, Hoogendijk WJ, et al. Cognitive inflexibility in obsessive-compulsive disorder and major depression is associated with distinct neural correlates. PLoS ONE. 2013;8:e59600.

  55. Saxena S, Brody AL, Ho ML, Alborzian S, Ho MK, Maidment KM, et al. Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently. Biol Psychiatry. 2001;50:159–70.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge support from the National Natural Foundation of China (81671365). The funder played no role in the preparation, review, or approval of the paper or decision to submit the paper for publication. We thank Tao Lou, Xingxia Zhu, Xiao-Xia Li, Min Sun, Hua Zheng, and Qiang Li from the Second Affiliated Hospital of Xinxiang Medical University for their efforts on data collection.

Author information

Author notes

  1. These authors contributed equally: Zongya Zhao, Chang-Hong Wang, Jian-Dong Ma

Authors and Affiliations

  1. The Second Hospital of Xinxiang Medical University, Xinxiang Medical University, Xinxiang City, Henan Province, PR China

    Zongya Zhao, Chang-Hong Wang, Jian-Dong Ma, Xiaowen Shan, Li-Jing Shi, Xunan Wang, De-En Sang, Hong-Zeng Zhao & Xian-Zhang Hu

  2. School of Medical Engineering, Xinxiang Medical University, Xinxiang, Henan Province, PR China

    Zongya Zhao

  3. The Second People’s Hospital of Shangqiu, Shangqiu City, Henan Province, PR China

    Xiaowen Shan

  4. The People’s Hospital of Xuchang, Xuchang City, Henan Province, PR China

    Xunan Wang

  5. The Fifth People’s Hospital of Kaifeng, Kaifeng City, Henan Province, PR China

    Ping Huang, Shao-Jie Kou & Zhi-Rong Li

  6. The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, PR China

    Heng-Fen Li

  7. Workstation of Henan Province for Psychiatry Experts, Kaifeng City, Henan Province, PR China

    Shao-Jie Kou & Xian-Zhang Hu

  8. Zhengzhou University Affiliated Zhengzhou Central Hospital, Zhengzhou City, Henan Province, PR China

    Hong-Kai Lian

Authors
  1. Zongya Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chang-Hong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jian-Dong Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaowen Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Li-Jing Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xunan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ping Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Heng-Fen Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. De-En Sang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shao-Jie Kou
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Zhi-Rong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Hong-Zeng Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Hong-Kai Lian
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Xian-Zhang Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xian-Zhang Hu.

Ethics declarations

Conflict of interest

The author declares no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, Z., Wang, CH., Ma, JD. et al. Decreased left amygdala functional connectivity by cognitive-coping therapy in obsessive-compulsive disorder. Mol Psychiatry 26, 6952–6962 (2021). https://doi.org/10.1038/s41380-021-01131-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41380-021-01131-z

Search

Advanced search

Quick links