Self-blame in major depression: a randomised pilot trial comparing fMRI neurofeedback with self-guided psychological strategies

Tanja Jaeckle, Steven C R Williams, Gareth J Barker, Rodrigo Basilio, Ewan Carr, Kimberley Goldsmith, Alessandro Colasanti, Vincent Giampietro, Anthony Cleare, Allan H Young, Jorge Moll, Roland Zahn, Tanja Jaeckle, Steven C R Williams, Gareth J Barker, Rodrigo Basilio, Ewan Carr, Kimberley Goldsmith, Alessandro Colasanti, Vincent Giampietro, Anthony Cleare, Allan H Young, Jorge Moll, Roland Zahn

Abstract

Background: Overgeneralised self-blame and worthlessness are key symptoms of major depressive disorder (MDD) and have previously been associated with self-blame-selective changes in connectivity between right superior anterior temporal lobe (rSATL) and subgenual frontal cortices. Another study showed that remitted MDD patients were able to modulate this neural signature using functional magnetic resonance imaging (fMRI) neurofeedback training, thereby increasing their self-esteem. The feasibility and potential of using this approach in symptomatic MDD were unknown.

Method: This single-blind pre-registered randomised controlled pilot trial probed a novel self-guided psychological intervention with and without additional rSATL-posterior subgenual cortex (BA25) fMRI neurofeedback, targeting self-blaming emotions in people with insufficiently recovered MDD and early treatment-resistance (n = 43, n = 35 completers). Participants completed three weekly self-guided sessions to rebalance self-blaming biases.

Results: As predicted, neurofeedback led to a training-induced reduction in rSATL-BA25 connectivity for self-blame v. other-blame. Both interventions were safe and resulted in a 46% reduction on the Beck Depression Inventory-II, our primary outcome, with no group differences. Secondary analyses, however, revealed that patients without DSM-5-defined anxious distress showed a superior response to neurofeedback compared with the psychological intervention, and the opposite pattern in anxious MDD. As predicted, symptom remission was associated with increases in self-esteem and this correlated with the frequency with which participants employed the psychological strategies in daily life.

Conclusions: These findings suggest that self-blame-rebalance neurofeedback may be superior over a solely psychological intervention in non-anxious MDD, although further confirmatory studies are needed. Simple self-guided strategies tackling self-blame were beneficial, but need to be compared against treatment-as-usual in further trials. https://doi.org/10.1186/ISRCTN10526888.

Keywords: Anger; Brodmann Area 25; anterior temporal lobe; guilt; major depressive disorder; neurofeedback; psychotherapy; real-time fMRI; social cognition; subgenual cingulate cortex.

Conflict of interest statement

RB, JM, and RZ are affiliated with IDOR, which owns the IP for the neurofeedback software FRIEND, which is made freely available in keeping with its not-for-profit mission. AHY is a consultant to Johnson & Johnson and Livanova. AHY has given paid lectures and sat on advisory boards for the following companies with drugs used in affective and related disorders: Astrazenaca, Eli Lilly, Lundbeck, Sunovion, Servier, Livanova, Janssen, Allegan, Bionomics, Sumitomo Dainippon Pharma, COMPASS. AHY has received honoraria for attending advisory boards and presenting talks at meetings organised by LivaNova. AHY is the Principal Investigator of trials of Esketamine, Vagus Nerve Stimulation, and Psilocybin in Depression. AHY has received grant funding (past and present) from the following: NIMH (USA); CIHR (Canada); NARSAD (USA); Stanley Medical Research Institute (USA); MRC (UK); Wellcome Trust (UK); Royal College of Physicians (Edin); BMA (UK); UBC-VGH Foundation (Canada); WEDC (Canada); CCS Depression Research Fund (Canada); MSFHR (Canada); NIHR (UK); Janssen (UK). AHY has no shareholdings in pharmaceutical companies. In the last three years, AJC has received honoraria for speaking from Lundbeck, honoraria for consulting from Allergan, Livanova, Janssen and Lundbeck, and sponsorship for attending an academic conference from Janssen. RZ is a private psychiatrist service provider at The London Depression Institute and co-investigator on a Livanova-funded observational study of Vagus Nerve Stimulation for Depression. RZ has received honoraria for talks at medical symposia sponsored by Lundbeck as well as Janssen. He has collaborated with EMIS PLC and advises Depsee Ltd. RZ and JM are affiliated with Scients Institute, Palo Alto. KG reports grants from NIHR, Stroke Association, National Institutes of Health (US) and Juvenile Diabetes Research Foundation (US) during the conduct of the study. EC reports personal fees from NIHR during the conduct of the study. GJB receives honoraria from GE Healthcare for teaching and is a patent holder on US patent number US 9903930 ‘RF pulses for magnetic resonance’. The other authors report no competing interests.

Figures

Fig. 1.
Fig. 1.
Relative change in functional connectivity between rSATL and posterior SC in the self-blame and other-blame condition, measured as Cohen's D for regression coefficient means for time series pre- and post-fMRI neurofeedback training, comparing the first and final treatment session. See Table 4 for statistics.
Fig. 2.
Fig. 2.
The results of a secondary analysis are displayed which stratified our primary outcome by anxious distress features, the most frequent major depressive disorder (MDD) subtype in our trial (n = 21 out of n = 35, Structured Clinical Interview for DSM5). Plotted are post-treatment BDI-II estimated marginal means of MDD patients with and without anxious distress in both treatment groups (fMRI neurofeedback group: n = 19; psychological intervention group: n = 16). Covariates appearing in the model are evaluated at the estimated baseline BDI-II value of 28.6 points.

References

    1. Abramson, L. Y., Seligman, M. E., & Teasdale, J. D. (1978). Learned helplessness in humans: Critique and reformulation. Journal of Abnormal Psychology, 87(1), 49–74. .
    1. APA. (2013). Diagnostic and statistical manual of mental disorders: DSM-5 (5th ed.). Washington D.C: American Psychiatric Association.
    1. Basilio, R., Garrido, G. J., Sato, J. R., Hoefle, S., Melo, B. R., Pamplona, F. A., … Moll, J. (2015). FRIEND Engine framework: A real-time neurofeedback client-server system for neuroimaging studies. Frontiers in Behavioral Neuroscience, 9, 3. 10.3389/fnbeh.2015.00003.
    1. Beck, A. T., Rush, A. J., Shaw, B. F., & Emery, G. (1979). Cognitive therapy of depression. New York, N.Y: Guilford Press.
    1. Beck, A. T., Steer, R. A., & Brown, G. K. (1996). Beck depression inventory-II. San Antonio, TX: Psychological Corporation.
    1. Coffman, C. J., Edelman, D., & Woolson, R. F. (2016). To condition or not condition? Analysing ‘change’ in longitudinal randomised controlled trials. BMJ Open, 6(12), e013096. 10.1136/bmjopen-2016-013096.
    1. Drevets, W. C., & Savitz, J. (2008). The subgenual anterior cingulate cortex in mood disorders. Cns Spectrums, 13(8), 663–681, <Go to ISI>://WOS:000260085400005.
    1. Dunlop, B. W., Rajendra, J. K., Craighead, W. E., Kelley, M. E., McGrath, C. L., Choi, K. S., … Mayberg, H. S. (2017). Functional connectivity of the subcallosal cingulate cortex and differential outcomes to treatment with cognitive-behavioral therapy or antidepressant medication for major depressive disorder. American Journal of Psychiatry, 174(6), 533–545. 10.1176/appi.ajp.2016.16050518.
    1. Faehndrich, E., & Stieglitz, R. D. (2007). Leitfaden zur erfassung des psychopathologischen befundes, halbstrukturiertes interview anhand des AMDP-systems (3rd ed.). Goettingen: Hogrefe Verlag.
    1. Faul, F., Erdfelder, E., Buchner, A., & Lang, A. G. (2009). Statistical power analyses using G*power 3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41(4), 1149–1160. 10.3758/BRM.41.4.1149.
    1. Feise, R. J. (2002). Do multiple outcome measures require p-value adjustment? BMC Medical Research Methodology, 2, 8. .
    1. Fisher, L. D. (1990). Intention to treat in clinical trials. Statistical issues in drug research and development. .
    1. Gilbert, P.. (2010). Compassion focused therapy: Distinctive features (pp. 3–5). Hove: Routledge.
    1. Green, S., Lambon Ralph, M. A., Moll, J., Deakin, J. F., & Zahn, R. (2012). Guilt-selective functional disconnection of anterior temporal and subgenual cortices in major depressive disorder. Archives of General Psychiatry, 69(10), 1014–1021. 10.1001/archgenpsychiatry.2012.135.
    1. Green, S., Moll, J., Deakin, J. F., Hulleman, J., & Zahn, R. (2013). Proneness to decreased negative emotions in major depressive disorder when blaming others rather than oneself. Psychopathology, 46(1), 34–44. 10.1159/000338632.
    1. Hamilton, J. P., Glover, G. H., Bagarinao, E., Chang, C., Mackey, S., Sacchet, M. D., & Gotlib, I. H. (2016). Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder. Psychiatry Res Neuroimaging, 249, 91–96. 10.1016/j.pscychresns.2016.01.016.
    1. Keller, M. B., Lavori, P. W., Friedman, B., Nielsen, E., Endicott, J., McDonald-Scott, P., & Andreasen, N. C. (1987). The longitudinal interval follow-up evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies. Archives of General Psychiatry, 44(6), 540–548. .
    1. Linden, D. E., Habes, I., Johnston, S. J., Linden, S., Tatineni, R., Subramanian, L., … Goebel, R. (2012). Real-time self-regulation of emotion networks in patients with depression. PloS One, 7(6), e38115. 10.1371/journal.pone.0038115.
    1. Lythe, K. E., Moll, J., Gethin, J. A., Workman, C. I., Green, S., Lambon Ralph, M. A., … Zahn, R. (2015). Self-blame-Selective hyperconnectivity between anterior temporal and subgenual cortices and prediction of recurrent depressive episodes. JAMA Psychiatry, 72(11), 1119–1126. 10.1001/jamapsychiatry.2015.1813.
    1. McNair, D., Lorr, M., & Doppleman, L. (1971). POMS Manual for the profile of mood states. San Diego, CA: Educational and Industrial Testing Service.
    1. Mehler, D. M. A., Sokunbi, M. O., Habes, I., Barawi, K., Subramanian, L., Range, M., … Linden, D. E. J. (2018). Targeting the affective brain-a randomized controlled trial of real-time fMRI neurofeedback in patients with depression. Neuropsychopharmacology, 43(13), 2578–2585. 10.1038/s41386-018-0126-5.
    1. Moll, J., Weingartner, J. H., Bado, P., Basilio, R., Sato, J. R., Melo, B. R., … Zahn, R. (2014). Voluntary enhancement of neural signatures of affiliative emotion using FMRI neurofeedback. PloS One, 9(5), e97343. 10.1371/journal.pone.0097343.
    1. Montgomery, S. A., & Åsberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal of Psychiatry, 134(4), 382–389.
    1. O'Connor, L. E., Berry, J. W., Weiss, J., & Gilbert, P. (2002). Guilt, fear, submission, and empathy in depression. Journal of Affective Disorders, 71(1–3), 19–27. .
    1. Price, J. L., & Drevets, W. C. (2010). Neurocircuitry of mood disorders. Neuropsychopharmacology, 35(1), 192–216.
    1. Rance, M., Walsh, C., Sukhodolsky, D. G., Pittman, B., Qiu, M., Kichuk, S. A., … Hampson, M. (2018). Time course of clinical change following neurofeedback. Neuroimage, 181, 807–813. 10.1016/j.neuroimage.2018.05.001.
    1. Ressler, K. J., & Mayberg, H. S. (2007). Targeting abnormal neural circuits in mood and anxiety disorders: From the laboratory to the clinic. Nature Neuroscience, 10(9), 1116–1124.
    1. Ros, T., Enriquez-Geppert, S., Zotev, V., Young, K. D., Wood, G., Whitfield-Gabrieli, S., … Thibault, R. T. (2020). Consensus on the reporting and experimental design of clinical and cognitive-behavioural neurofeedback studies (CRED-nf checklist). Brain, 143(6), 1674–1685. 10.1093/brain/awaa009.
    1. Rosenthal, R., & Rosnow, R. L. (1991). Essentials of behavioral research: Methods and data analysis (2nd ed.). New York: McGraw Hill.
    1. Rush, A. J., Trivedi, M. H., Ibrahim, H. M., Carmody, T. J., Arnow, B., Klein, D. N., … Keller, M. B. (2003). The 16-item quick inventory of depressive symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): A psychometric evaluation in patients with chronic major depression. Biological Psychiatry, 54(5), 573–583. .
    1. Sato, J. R., Basilio, R., Paiva, F. F., Garrido, G. J., Bramati, I. E., Bado, P., … Moll, J. (2013). Real-time fMRI pattern decoding and neurofeedback using FRIEND: An FSL-integrated BCI toolbox. PloS One, 8(12), e81658. 10.1371/journal.pone.0081658.
    1. Siegle, G. J., Carter, C. S., & Thase, M. E. (2006). Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy. American Journal of Psychiatry, 163(4), 735–738. 10.1176/appi.ajp.163.4.735.
    1. Tangney, J. P., Stuewig, J., & Mashek, D. J. (2007). Moral emotions and moral behavior. Annual Review of Psychology, 58, 345–372. 10.1146/annurev.psych.56.091103.070145.
    1. Teare, M. D., Dimairo, M., Shephard, N., Hayman, A., Whitehead, A., & Walters, S. J. (2014). Sample size requirements to estimate key design parameters from external pilot randomised controlled trials: A simulation study. Trials, 15, 264. 10.1186/1745-6215-15-264.
    1. Walsh, B. T., Seidman, S. N., Sysko, R., & Gould, M. (2002). Placebo response in studies of major depression: Variable, substantial, and growing. JAMA, 287(14), 1840–1847. .
    1. Watson, D., Clark, L. A., & Carey, G. (1988). Positive and negative affectivity and their relation to anxiety and depressive disorders. Journal of Abnormal Psychology, 97(3), 346–353, <Go to ISI>://A1988P577200015.
    1. Young, K. D., Misaki, M., Harmer, C. J., Victor, T., Zotev, V., Phillips, R., … Bodurka, J. (2017a). Real-time functional magnetic resonance imaging amygdala neurofeedback changes positive information processing in major depressive disorder. Biological Psychiatry, 82(8), 578–586.
    1. Young, K. D., Siegle, G. J., Misaki, M., Zotev, V., Phillips, R., Drevets, W. C., & Bodurka, J. (2018a). Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder. Neuroimage. Clinical, 17, 691–703.
    1. Young, K. D., Siegle, G. J., Zotev, V., Phillips, R., Misaki, M., Yuan, H., … Bodurka, J. (2017b). Randomized clinical trial of real-time fMRI amygdala neurofeedback for major depressive disorder: Effects on symptoms and autobiographical memory recall. American Journal of Psychiatry, 174(8), 748–755.
    1. Young, K. D., Zotev, V., Phillips, R., Misaki, M., Drevets, W. C., & Bodurka, J. (2018b). Amygdala real-time functional magnetic resonance imaging neurofeedback for major depressive disorder: A review. Psychiatry and Clinical Neurosciences, 72(7), 466–481. 10.1111/pcn.12665.
    1. Young, K. D., Zotev, V., Phillips, R., Misaki, M., Yuan, H., Drevets, W. C., & Bodurka, J. (2014). Real-time FMRI neurofeedback training of amygdala activity in patients with major depressive disorder. PloS One, 9(2), e88785. 10.1371/journal.pone.0088785.
    1. Yuan, H., Young, K. D., Phillips, R., Zotev, V., Misaki, M., & Bodurka, J. (2014). Resting-state functional connectivity modulation and sustained changes after real-time functional magnetic resonance imaging neurofeedback training in depression. Brain Connectivity, 4(9), 690–701. 10.1089/brain.2014.0262.
    1. Zaehringer, J., Ende, G., Santangelo, P., Kleindienst, N., Ruf, M., Bertsch, K., … Paret, C. (2019). Improved emotion regulation after neurofeedback: A single-arm trial in patients with borderline personality disorder. NeuroImage: Clinical, 24, 102032. 10.1016/j.nicl.2019.102032.
    1. Zahn, R., de Oliveira-Souza, R., & Moll, J. (2020). Moral motivation and the basal forebrain [Review]. Neuroscience and Biobehavioral Reviews, 108, 207–217. 10.1016/j.neubiorev.2019.10.022.
    1. Zahn, R., Lythe, K. E., Gethin, J. A., Green, S., Deakin, J. F., Workman, C., & Moll, J. (2015). Negative emotions towards others are diminished in remitted major depression. European Psychiatry, 30(4), 448–453. 10.1016/j.eurpsy.2015.02.005.
    1. Zahn, R., Lythe, K. E., Gethin, J. A., Green, S., Deakin, J. F., Young, A. H., & Moll, J. (2015b). The role of self-blame and worthlessness in the psychopathology of major depressive disorder. Journal of Affective Disorders, 186, 337–341. 10.1016/j.jad.2015.08.001.
    1. Zahn, R., Weingartner, J. H., Basilio, R., Bado, P., Mattos, P., Sato, J. R., … Moll, J. (2019). Blame-rebalance fMRI neurofeedback in major depressive disorder: A randomised proof-of-concept trial. NeuroImage: Clinical, 101992.
    1. Zotev, V., Phillips, R., Yuan, H., Misaki, M., & Bodurka, J. (2014). Self-regulation of human brain activity using simultaneous real-time fMRI and EEG neurofeedback. Neuroimage, 85(Pt 3), 985–995.
    1. Zotev, V., Yuan, H., Misaki, M., Phillips, R., Young, K. D., Feldner, M. T., & Bodurka, J. (2016). Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression. Neuroimage. Clinical, 11, 224–238. 10.1016/j.nicl.2016.02.003.

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