Using Electronically Delivered Therapy and Brain Imaging to Understand Obsessive-Compulsive Disorder Pathophysiology: Protocol for a Pilot Study

Callum Stephenson, Niloufar Malakouti, Joseph Y Nashed, Tim Salomons, Douglas J Cook, Roumen Milev, Nazanin Alavi, Callum Stephenson, Niloufar Malakouti, Joseph Y Nashed, Tim Salomons, Douglas J Cook, Roumen Milev, Nazanin Alavi

Abstract

Background: Obsessive-compulsive disorder (OCD) is a debilitating and prevalent anxiety disorder. Although the basal ganglia and frontal cortex are the brain regions that are most commonly hypothesized to be involved in OCD, the exact pathophysiology is unknown. By observing the effects of proven treatments on brain activation levels, the cause of OCD can be better understood. Currently, the gold standard treatment for OCD is cognitive behavioral therapy (CBT) with exposure and response prevention. However, this is often temporally and geographically inaccessible, time consuming, and costly. Fortunately, CBT can be effectively delivered using the internet (electronically delivered CBT [e-CBT]) because of its structured nature, thus addressing these barriers.

Objective: The aims of this study are to implement an e-CBT program for OCD and to observe its effects on brain activation levels using functional magnetic resonance imaging (MRI). It is hypothesized that brain activation levels in the basal ganglia and frontal cortex will decrease after treatment.

Methods: Individuals with OCD will be offered a 16-week e-CBT program with exposure and response prevention mirroring in-person CBT content and administered through a secure web-based platform. The efficacy of the treatment will be evaluated using clinically validated symptomology questionnaires at baseline, at week 8, and after treatment (week 16). Using functional MRI at baseline and after treatment, brain activation levels will be assessed in the resting state and while exposed to anxiety-inducing images (eg, dirty dishes if cleanliness is an obsession). The effects of treatment on brain activation levels and the correlation between symptom changes and activation levels will be analyzed.

Results: The study received initial ethics approval in December 2020, and participant recruitment began in January 2021. Participant recruitment has been conducted through social media advertisements, physical advertisements, and physician referrals. To date, 5 participants have been recruited. Data collection is expected to conclude by January 2022, and data analysis is expected to be completed by February 2022.

Conclusions: The findings from this study can further our understanding of the causation of OCD and help develop more effective treatments for this disorder.

Trial registration: ClinicalTrials.gov NCT04630197; https://ichgcp.net/clinical-trials-registry/NCT04630197.

International registered report identifier (irrid): PRR1-10.2196/30726.

Keywords: brain imaging; cognitive behavioral therapy; eHealth; electronic; exposure ritual prevention; functional magnetic resonance imaging; mental health; obsessive-compulsive disorder.

Conflict of interest statement

Conflicts of Interest: NA is a cofounder of the care delivery platform used in this study (Online Psychotherapy Tool [OPTT]) and has ownership stakes in OPTT Inc. RM has received consulting and speaking honoraria from AbbVie, Allergan, Eisai, Janssen, KYE, Lallemand, Lundbeck, Otsuka, and Sunovion, and research grants from CAN-BIND, Canadian Institutes of Health Research, Janssen, Lallemand, Lundbeck, Nubiyota, OBI, and Ontario Mental Health Foundation.

©Callum Stephenson, Niloufar Malakouti, Joseph Y Nashed, Tim Salomons, Douglas J Cook, Roumen Milev, Nazanin Alavi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 14.09.2021.

References

    1. Osland S, Arnold PD, Pringsheim T. The prevalence of diagnosed obsessive compulsive disorder and associated comorbidities: A population-based Canadian study. Psychiatry Res. 2018 Oct;268:137–42. doi: 10.1016/j.psychres.2018.07.018.S0165-1781(18)30444-X
    1. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2005 Jun;62(6):593–602. doi: 10.1001/archpsyc.62.6.593.62/6/593
    1. Pauls DL. The genetics of obsessive-compulsive disorder: a review. Dialogues Clin Neurosci. 2010;12(2):149–63.
    1. Sternberger LG, Burns GL. Compulsive activity checklist and the maudsley obsessional-compulsive inventory: Psychometric properties of two measures of obsessive-compulsive disorder. Behav Ther. 1990;21(1):117–27. doi: 10.1016/s0005-7894(05)80193-5.
    1. Stuker PB, Adams HE, editors. Comprehensive Handbook of Psychopathology. Boston: Springer; 1993. Obsessive-compulsive disorders; pp. 129–44.
    1. Comer JS, Kendall PC, Franklin ME, Hudson JL, Pimentel SS. Obsessing/worrying about the overlap between obsessive-compulsive disorder and generalized anxiety disorder in youth. Clin Psychol Rev. 2004 Oct;24(6):663–83. doi: 10.1016/j.cpr.2004.04.004.S0272735804000479
    1. Newth S, Rachman S. The concealment of obsessions. Behav Res Ther. 2001 Apr;39(4):457–64. doi: 10.1016/s0005-7967(00)00006-1.S0005-7967(00)00006-1
    1. Foa EB, Kozak MJ, Goodman WK, Hollander E, Jenike MA, Rasmussen SA. DSM-IV field trial: obsessive-compulsive disorder. Am J Psychiatry. 1995 Jan;152(1):90–6. doi: 10.1176/ajp.152.1.90.
    1. Rachman S. A cognitive theory of obsessions. Behav Res Ther. 1997 Sep;35(9):793–802. doi: 10.1016/s0005-7967(97)00040-5.S0005-7967(97)00040-5
    1. Salkovskis PM. Obsessional-compulsive problems: a cognitive-behavioural analysis. Behav Res Ther. 1985;23(5):571–83. doi: 10.1016/0005-7967(85)90105-6.0005-7967(85)90105-6
    1. Lawrence PJ, Williams TI. Pathways to inflated responsibility beliefs in adolescent obsessive-compulsive disorder: a preliminary investigation. Behav Cogn Psychother. 2011 Mar;39(2):229–34. doi: 10.1017/S1352465810000810.S1352465810000810
    1. Rachman S. Obsessions, responsibility and guilt. Behav Res Ther. 1993 Feb;31(2):149–54. doi: 10.1016/0005-7967(93)90066-4.0005-7967(93)90066-4
    1. Saxena S, Rauch SL. Functional neuroimaging and the neuroanatomy of obsessive-compulsive disorder. Psychiatr Clin North Am. 2000 Sep;23(3):563–86. doi: 10.1016/s0193-953x(05)70181-7.S0193-953X(05)70181-7
    1. Saxena S, Bota RG, Brody AL. Brain-behavior relationships in obsessive-compulsive disorder. Semin Clin Neuropsychiatry. 2001 Apr;6(2):82–101. doi: 10.1053/scnp.2001.21833.S1084361201000107
    1. Schwartz JM. Neuroanatomical aspects of cognitive-behavioural therapy response in obsessive-compulsive disorder. An evolving perspective on brain and behaviour. Br J Psychiatry Suppl. 1998;(35):38–44.
    1. Bandelow B, Michaelis S, Wedekind D. Treatment of anxiety disorders. Dialogues Clin Neurosci. 2017 Jun;19(2):93–107.
    1. National Institute of Mental Health Obsessive-compulsive disorder: When unwanted thoughts or repetitive behaviors take over. NIH. 2020:1. doi: 10.1037/e620122011-001.
    1. Hunsley J, Elliott K, Therrien Z. The efficacy and effectiveness of psychological treatments for mood, anxiety, and related disorders. Can Psychol/Psychologie canadienne. 2014;55(3):161–76. doi: 10.1037/a0036933.
    1. National Institute for Health and Care Excellence Obsessive-compulsive disorder and body dysmorphic disorder: treatment. Clinical Guidelines. 2005:1. doi: 10.1016/b978-008044701-8/50012-7.
    1. Beck A, Rush A, Shaw B, Emergy G. Cognitive Therapy of Depression. New York: Guilford Press; 1987. pp. 1–425.
    1. Margraf J, Barlow DH, Clark DM, Telch MJ. Psychological treatment of panic: work in progress on outcome, active ingredients, and follow-up. Behav Res Ther. 1993 Jan;31(1):1–8. doi: 10.1016/0005-7967(93)90036-t.0005-7967(93)90036-T
    1. Whittal ML, Thordarson DS, McLean PD. Treatment of obsessive-compulsive disorder: cognitive behavior therapy vs. exposure and response prevention. Behav Res Ther. 2005 Dec;43(12):1559–76. doi: 10.1016/j.brat.2004.11.012.S0005-7967(05)00006-9
    1. Wilhelm S, Steketee G. Cognitive Therapy for Obsessive-Compulsive Disorder: A Guide for Professionals. Oakland, CA: New Harbinger Publications; 2005. pp. 1–240.
    1. Storch EA, Merlo LJ. Obsessive-compulsive disorder: strategies for using CBT and pharmacotherapy. J Fam Pract. 2006 Apr;55(4):329–33.jfp_0406_5504d
    1. Wootton BM, Titov N, Dear BF, Spence J, Andrews G, Johnston L, Solley K. An Internet administered treatment program for obsessive-compulsive disorder: a feasibility study. J Anxiety Disord. 2011 Dec;25(8):1102–7. doi: 10.1016/j.janxdis.2011.07.009.S0887-6185(11)00135-6
    1. Matsumoto K, Sutoh C, Asano K, Seki Y, Urao Y, Yokoo M, Takanashi R, Yoshida T, Tanaka M, Noguchi R, Nagata S, Oshiro K, Numata N, Hirose M, Yoshimura K, Nagai K, Sato Y, Kishimoto T, Nakagawa A, Shimizu E. Internet-based cognitive behavioral therapy with real-time therapist support via videoconference for patients with obsessive-compulsive disorder, panic disorder, and social anxiety disorder: pilot single-arm trial. J Med Internet Res. 2018 Dec 17;20(12):e12091. doi: 10.2196/12091. v20i12e12091
    1. Patel SR, Wheaton MG, Andersson E, Rück C, Schmidt AB, La Lima CN, Galfavy H, Pascucci O, Myers RW, Dixon LB, Simpson HB. Acceptability, feasibility, and effectiveness of internet-based cognitive-behavioral therapy for obsessive-compulsive disorder in New York. Behav Ther. 2018 Jul;49(4):631–41. doi: 10.1016/j.beth.2017.09.003. S0005-7894(17)30099-0
    1. Herbst N, Voderholzer U, Thiel N, Schaub R, Knaevelsrud C, Stracke S, Hertenstein E, Nissen C, Külz AK. No talking, just writing! Efficacy of an internet-based cognitive behavioral therapy with exposure and response prevention in obsessive compulsive disorder. Psychother Psychosom. 2014;83(3):165–75. doi: 10.1159/000357570.000357570
    1. Andersson E, Enander J, Andrén P, Hedman E, Ljótsson B, Hursti T, Bergström J, Kaldo V, Lindefors N, Andersson G, Rück C. Internet-based cognitive behaviour therapy for obsessive-compulsive disorder: a randomized controlled trial. Psychol Med. 2012 Oct;42(10):2193–203. doi: 10.1017/S0033291712000244. S0033291712000244
    1. Mahoney AE, Mackenzie A, Williams AD, Smith J, Andrews G. Internet cognitive behavioural treatment for obsessive compulsive disorder: A randomised controlled trial. Behav Res Ther. 2014 Dec;63:99–106. doi: 10.1016/j.brat.2014.09.012.S0005-7967(14)00163-6
    1. Rauch SL, Dougherty DD, Shin LM, Alpert NM, Manzo P, Leahy L, Fischman AJ, Jenike MA, Baer L. Neural correlates of factor-analyzed OCD symptom dimensions: A PET study. CNS spectr. 2014 Nov 07;3(7):37–43. doi: 10.1017/s1092852900006167.
    1. Rosenberg DR, Keshavan MS. A.E. Bennett Research Award. Toward a neurodevelopmental model of obsessive--compulsive disorder. Biol Psychiatry. 1998 May 01;43(9):623–40. doi: 10.1016/s0006-3223(97)00443-5.S0006322397004435
    1. Saxena S, Brody AL, Schwartz JM, Baxter LR. Neuroimaging and frontal-subcortical circuitry in obsessive-compulsive disorder. Br J Psychiatry Suppl. 1998;(35):26–37.
    1. Nelson AB, Kreitzer AC. Reassessing models of basal ganglia function and dysfunction. Annu Rev Neurosci. 2014;37:117–35. doi: 10.1146/annurev-neuro-071013-013916.
    1. Tamminga CA, Buchsbaum MS. Frontal cortex function. Am J Psychiatry. 2004 Dec;161(12):2178. doi: 10.1176/appi.ajp.161.12.2178.161/12/2178
    1. Zhong Z, Yang X, Cao R, Li P, Li Z, Lv L, Zhang D. Abnormalities of white matter microstructure in unmedicated patients with obsessive-compulsive disorder: Changes after cognitive behavioral therapy. Brain Behav. 2019 Feb;9(2):e01201. doi: 10.1002/brb3.1201. doi: 10.1002/brb3.1201.
    1. Whiteside SP, Port JD, Abramowitz JS. A meta-analysis of functional neuroimaging in obsessive-compulsive disorder. Psychiatry Res. 2004 Nov 15;132(1):69–79. doi: 10.1016/j.pscychresns.2004.07.001.S0925-4927(04)00082-4
    1. Pato MT, Pato CN, Pauls DL. Recent findings in the genetics of OCD. J Clin Psychiatry. 2002;63 Suppl 6:30–3.
    1. Pauls DL, Alsobrook JP. The inheritance of obsessive-compulsive disorder. Child Adolesc Psychiatr Clin N Am. 1999 Jul;8(3):481–96, viii.
    1. Taylor S, Coles ME, Abramowitz JS, Wu KD, Olatunji BO, Timpano KR, McKay D, Kim S, Carmin C, Tolin DF. How are dysfunctional beliefs related to obsessive-compulsive symptoms? J Cogn Psychother. 2010 Aug 01;24(3):165–76. doi: 10.1891/0889-8391.24.3.165.
    1. Beutel ME, Stark R, Pan H, Silbersweig D, Dietrich S. Changes of brain activation pre- post short-term psychodynamic inpatient psychotherapy: an fMRI study of panic disorder patients. Psychiatry Res. 2010 Nov 30;184(2):96–104. doi: 10.1016/j.pscychresns.2010.06.005.S0925-4927(10)00223-4
    1. Steiger VR, Brühl AB, Weidt S, Delsignore A, Rufer M, Jäncke L, Herwig U, Hänggi J. Pattern of structural brain changes in social anxiety disorder after cognitive behavioral group therapy: a longitudinal multimodal MRI study. Mol Psychiatry. 2017 Aug;22(8):1164–71. doi: 10.1038/mp.2016.217.mp2016217
    1. Norman LJ, Mannella KA, Yang H, Angstadt M, Abelson JL, Himle JA, Fitzgerald KD, Taylor SF. Treatment-specific associations between brain activation and symptom reduction in OCD following CBT: a randomized FMRI trial. Am J Psychiatry. 2021 Jan 01;178(1):39–47. doi: 10.1176/appi.ajp.2020.19080886.
    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5 Ed. Arlington, VA: American Psychiatric Association; 2013. pp. 1–991.
    1. Lang P, Bradley M, Cuthbert B. International affective picture system (IAPS): Affective ratings of pictures and instruction manual. Technical Report A-8. University of Florida, Gainesville, FL. 2008:1. doi: 10.1037/t66667-000.
    1. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, Charney DS. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989 Nov;46(11):1012–6. doi: 10.1001/archpsyc.1989.01810110054008.
    1. Abramowitz JS, Deacon BJ. Psychometric properties and construct validity of the Obsessive-Compulsive Inventory--Revised: Replication and extension with a clinical sample. J Anxiety Disord. 2006;20(8):1016–35. doi: 10.1016/j.janxdis.2006.03.001.S0887-6185(06)00037-5
    1. Endicott J, Nee J, Harrison W, Blumenthal R. Quality of Life Enjoyment and Satisfaction Questionnaire: a new measure. Psychopharmacol Bull. 1993;29(2):321–6.
    1. Leon AC, Olfson M, Portera L, Farber L, Sheehan DV. Assessing psychiatric impairment in primary care with the Sheehan Disability Scale. Int J Psychiatry Med. 1997;27(2):93–105.
    1. Swift JK, Greenberg RP. A treatment by disorder meta-analysis of dropout from psychotherapy. J Psychother Integr. 2014;24(3):193–207. doi: 10.1037/a0037512.
    1. Andrews G, Basu A, Cuijpers P, Craske M, McEvoy P, English C, Newby J. Computer therapy for the anxiety and depression disorders is effective, acceptable and practical health care: An updated meta-analysis. J Anx Disord. 2018 Apr;55:70–8. doi: 10.1016/j.janxdis.2018.01.001.
    1. Etzelmueller A, Vis C, Karyotaki E, Baumeister H, Titov N, Berking M, Cuijpers P, Riper H, Ebert DD. Effects of internet-based cognitive behavioral therapy in routine care for adults in treatment for depression and anxiety: systematic review and meta-analysis. J Med Internet Res. 2020 Aug 31;22(8):e18100. doi: 10.2196/18100.
    1. Guo S, Deng W, Wang H, Liu J, Liu X, Yang X, He C, Zhang Q, Liu B, Dong X, Yang Z, Li Z, Li X. The efficacy of internet-based cognitive behavioural therapy for social anxiety disorder: A systematic review and meta-analysis. Clin Psychol Psychother. 2020 Nov 10;28(3):656–68. doi: 10.1002/cpp.2528.
    1. Andersson E, Enander J, Andrén P, Hedman E, Ljótsson B, Hursti T, Bergström J, Kaldo V, Lindefors N, Andersson G, Rück C. Internet-based cognitive behaviour therapy for obsessive–compulsive disorder: a randomized controlled trial. Psychol Med. 2012 Feb 21;42(10):2193–203. doi: 10.1017/s0033291712000244.
    1. ALAVI N, HIRJI A. The efficacy of powerpoint-based CBT delivered through email. J Psychiat Pract. 2020;26(2):89–100. doi: 10.1097/pra.0000000000000455.
    1. Andersson JL, Ashburner J, Friston K. A global estimator unbiased by local changes. Neuroimage. 2001 Jun;13(6 Pt 1):1193–206. doi: 10.1006/nimg.2001.0763.S1053-8119(01)90763-3
    1. Desjardins AE, Kiehl KA, Liddle PF. Removal of confounding effects of global signal in functional MRI analyses. Neuroimage. 2001 Apr;13(4):751–8. doi: 10.1006/nimg.2000.0719.S1053-8119(00)90719-5
    1. Worsley KJ, Liao CH, Aston J, Petre V, Duncan GH, Morales F, Evans AC. A general statistical analysis for fMRI data. Neuroimage. 2002 Jan;15(1):1–15. doi: 10.1006/nimg.2001.0933.S1053811901909334

Source: PubMed

3
S'abonner