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Neural predictors and effects of cognitive behavioral therapy for depression: the role of emotional reactivity and regulation

  • Harry Rubin-Falcone (a1) (a2), Jochen Weber (a3), Ronit Kishon (a1), Kevin Ochsner (a3), Lauren Delaparte (a4), Bruce Doré (a5), Sudha Raman (a1) (a2), Bryan T. Denny (a6), Maria A. Oquendo (a7), J. John Mann (a1) (a2) and Jeffrey M. Miller (a1) (a2)...

Abstract

Background

Cognitive behavioral therapy (CBT) is an effective treatment for many patients suffering from major depressive disorder (MDD), but predictors of treatment outcome are lacking, and little is known about its neural mechanisms. We recently identified longitudinal changes in neural correlates of conscious emotion regulation that scaled with clinical responses to CBT for MDD, using a negative autobiographical memory-based task.

Methods

We now examine the neural correlates of emotional reactivity and emotion regulation during viewing of emotionally salient images as predictors of treatment outcome with CBT for MDD, and the relationship between longitudinal change in functional magnetic resonance imaging (fMRI) responses and clinical outcomes. Thirty-two participants with current MDD underwent baseline MRI scanning followed by 14 sessions of CBT. The fMRI task measured emotional reactivity and emotion regulation on separate trials using standardized images from the International Affective Pictures System. Twenty-one participants completed post-treatment scanning. Last observation carried forward was used to estimate clinical outcome for non-completers.

Results

Pre-treatment emotional reactivity Blood Oxygen Level-Dependent (BOLD) signal within hippocampus including CA1 predicted worse treatment outcome. In contrast, better treatment outcome was associated with increased down-regulation of BOLD activity during emotion regulation from time 1 to time 2 in precuneus, occipital cortex, and middle frontal gyrus.

Conclusions

CBT may modulate the neural circuitry of emotion regulation. The neural correlates of emotional reactivity may be more strongly predictive of CBT outcome. The finding that treatment outcome was predicted by BOLD signal in CA1 may suggest overgeneralized memory as a negative prognostic factor in CBT outcome.

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Copyright

Corresponding author

Author for correspondence: Harry Rubin-Falcone, E-mail: harry.falcone@nyspi.columbi.edu

References

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Beck, AT (1979) Cognitive Therapy of Depression. New York: Guilford Press.
Beck, AT, Ward, CH, Mendelson, M, Moc, J and Erbauh, J (1961) An inventory for measuring depression. Archives of General Psychiatry 4, 5363.
Beck, AT, Kovacs, M and Weissman, A (1979) Assessment of suicidal intention: the Scale for Suicide Ideation. Journal of Consulting and Clinical Psychology 47, 343352.
Beck, JS (1995) Cognitive Therapy: Basics and Beyond. New York: Guilford Press.
Buhle, JT, Silvers, JA, Wager, TD, Lopez, R, Onyemekwu, C and Kober, H (2014) Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies. Cerebral Cortex 24, 29812990.
Burgess, PW, Gilbert, SJ and Dumontheil, I (2007) Function and localization within rostral prefrontal cortex (area 10). Philosophical Transactions of the Royal Society B: Biological Sciences 362, 887899.
Costafreda, SG, Khanna, A, Mourao-Miranda, J and Fu, CH (2009) Neural correlates of sad faces predict clinical remission to cognitive behavioural therapy in depression. NeuroReport 20, 637641.
Delaveau, P, Jabourian, M, Lemogne, C, Guionnet, S, Bergouignan, L and Fossati, P (2011) Brain effects of antidepressants in major depression: a meta-analysis of emotional processing studies. Journal of Affective Disorders 130, 6674.
Denny, BT and Ochsner, KN (2014) Behavioral effects of longitudinal training in cognitive reappraisal. Emotion 14, 425433.
Denny, BT, Fan, J, Liu, X, Ochsner, KN, Guerreri, S, Mayson, S, Rimsky, L, McMaster, A, New, AS, Goodman, M, Siever, LJ and Koenigsberg, HW (2015 a). Elevated amygdala activity during reappraisal anticipation predicts anxiety in avoidant personality disorder. Journal of Affective Disorders 172, 17.
Denny, BT, Inhoff, MC, Zerubavel, N, Davachi, L and Ochsner, KN (2015 b). Getting over it: long-lasting effects of emotion regulation on amygdala response. Psychological Science 26, 13771388.
DeRubeis, RJ, Siegle, GJ and Hollon, SD (2008). Cognitive therapy versus medication for depression: treatment outcomes and neural mechanisms. Nature Reviews Neuroscience 9, 788796.
Dorfel, D, Lamke, JP, Hummel, F, Wagner, U, Erk, S and Walter, H (2014) Common and differential neural networks of emotion regulation by detachment, reinterpretation, distraction, and expressive suppression: a comparative fMRI investigation. NeuroImage 101, 298309.
Drevets, WC (2003) Neuroimaging abnormalities in the amygdala in mood disorders. Annals of the New York Academy of Sciences 985, 420444.
Eklund, A, Nichols, TE and Knutsson, H (2016) Cluster failure: why fMRI inferences for spatial extent have inflated false-positive rates. Proceedings of the National Academy of Sciences of the United States of America 113, 79007905.
Fales, CL, Barch, DM, Rundle, MM, Mintun, MA, Mathews, J, Snyder, AZ and Sheline, YI (2009) Antidepressant treatment normalizes hypoactivity in dorsolateral prefrontal cortex during emotional interference processing in major depression. Journal of Affective Disorders 112, 206211.
First, M, Spitzer, R, Gibbon, M and Williams, J (1995) Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P, Version 2.0). New York: Biometrics Research Department, New York State Psychiatric Institute.
Fonzo, GA, Goodkind, MS, Oathes, DJ, Zaiko, YV, Harvey, M, Peng, KK, Weiss, ME, Thompson, AL, Zack, SE, Lindley, SE, Arnow, BA, Jo, B, Gross, JJ, Rothbaum, BO and Etkin, A (2017 a). PTSD psychotherapy outcome predicted by brain activation during emotional reactivity and regulation. The American Journal of Psychiatry 12, 11631174.
Fonzo, GA, Goodkind, MS, Oathes, DJ, Zaiko, YV, Harvey, M, Peng, KK, Weiss, ME, Thompson, AL, Zack, SE, Mills-Finnerty, CE, Rosenberg, BM, Edelstein, R, Wright, RN, Kole, CA, Lindley, SE, Arnow, BA, Jo, B, Gross, JJ, Rothbaum, BO and Etkin, A (2017 b). Selective effects of psychotherapy on frontopolar cortical function in PTSD. The American Journal of Psychiatry 12, 11751184.
Frith, CD, Friston, K, Liddle, PF and Frackowiak, RS (1991) Willed action and the prefrontal cortex in man: a study with PET. Proceedings of the Royal Society B: Biological Sciences 244, 241246.
Fu, CH, Williams, SC, Cleare, AJ, Scott, J, Mitterschiffthaler, MT and Walsh, ND (2008) Neural responses to sad facial expressions in major depression following cognitive behavioral therapy. Biological Psychiatry 64, 505512.
Gloaguen, V, Cottraux, J, Cucherat, M and Blackburn, IM (1998) A meta-analysis of the effects of cognitive therapy in depressed patients. Journal of Affective Disorders 49, 5972.
Golkar, A, Lonsdorf, TB, Olsson, A, Lindstrom, KM, Berrebi, J, Fransson, P, Schalling, M, Ingvar, M and Ohman, A (2012) Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation. PLoS ONE 7, e48107.
Gotlib, IH and Hammen, CL (2009) Handbook of Depression. New York, N.Y.: The Guilford Press.
Gotlib, IH and Joormann, J (2010) Cognition and depression: current status and future directions. Annual Review of Clinical Psychology 6, 285312.
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Heller, AS, Johnstone, T, Shackman, AJ, Light, SN, Peterson, MJ and Kolden, GG (2009) Reduced capacity to sustain positive emotion in major depression reflects diminished maintenance of fronto-striatal brain activation. Proceedings of the National Academy of Sciences of the United States of America 106, 2244522450.
Herold, D, Spengler, S, Sajonz, B, Usnich, T and Bermpohl, F (2016) Common and distinct networks for self-referential and social stimulus processing in the human brain. Brain Structure and Function 221, 34753485.
Hollon, SD, Thase, ME and Markowitz, JC (2002) Treatment and prevention of depression. Psychological Science in the Public Interest 3, 3977.
Johnstone, T, van Reekum, CM, Urry, HL, Kalin, NH and Davidson, RJ (2007) Failure to regulate: counterproductive recruitment of top-down prefrontal-subcortical circuitry in major depression. The Journal of Neuroscience 27, 88778884.
Kendler, KS, Karkowski, LM and Prescott, CA (1999) Causal relationship between stressful life events and the onset of major depression. The American Journal of Psychiatry 156, 837841.
Kircanski, K, Joormann, J and Gotlib, IH (2012) Cognitive aspects of depression. Wiley Interdisciplinary Reviews: Cognitive Science 3, 301313.
Lang, PJ, Greenwald, MK, Bradley, MM and Hamm, AO (1993) Looking at pictures: affective, facial, visceral, and behavioral reactions. Psychophysiology 30, 261273.
Leppanen, JM (2006) Emotional information processing in mood disorders: a review of behavioral and neuroimaging findings. Current Opinion in Psychiatry 19, 3439.
Linnman, C, Moulton, EA, Barmettler, G, Becerra, L and Borsook, D (2012) Neuroimaging of the periaqueductal gray: state of the field. NeuroImage 60, 505522.
Maldjian, JA, Laurienti, PJ, Kraft, RA and Burdette, JH (2003) An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. NeuroImage 19, 12331239.
Messina, I, Sambin, M, Palmieri, A and Viviani, R (2013) Neural correlates of psychotherapy in anxiety and depression: a meta-analysis. PLoS ONE 8, e74657.
Miller, JM, Schneck, N, Siegle, GJ, Chen, Y, Ogden, RT, Kikuchi, T, Oquendo, MA, Mann, JJ and Parsey, RV (2013) fMRI response to negative words and SSRI treatment outcome in major depressive disorder: a preliminary study. Psychiatry Research 214, 296305.
Ochsner, KN, Bunge, SA, Gross, JJ and Gabrieli, JD (2002) Rethinking feelings: an FMRI study of the cognitive regulation of emotion. Journal of Cognitive Neuroscience 14, 12151229.
Ochsner, KN, Ray, RD, Cooper, JC, Robertson, ER, Chopra, S, Gabrieli, JD and Gross, JJ (2004). For better or for worse: neural systems supporting the cognitive down- and up-regulation of negative emotion. NeuroImage 23, 483499.
Ritchey, M, Dolcos, F, Eddington, KM, Strauman, TJ and Cabeza, R (2011) Neural correlates of emotional processing in depression: changes with cognitive behavioral therapy and predictors of treatment response. Journal of Psychiatric Research 45, 577587.
Rosenblau, G, Sterzer, P, Stoy, M, Park, S, Friedel, E, Heinz, A, Pilhatsch, M, Bauer, M and Strohle, A (2012) Functional neuroanatomy of emotion processing in major depressive disorder is altered after successful antidepressant therapy. Journal of Psychopharmacology 26, 14241433.
Rubin-Falcone, H, Weber, J, Kishon, R, Ochsner, K, Delaparte, L, Dore, B, Zanderigo, F, Oquendo, MA, Mann, JJ and Miller, JM (2017) Longitudinal effects of cognitive behavioral therapy for depression on the neural correlates of emotion regulation. Psychiatry Research: Neuroimaging 271, 8290.
Schlichting, M, Zeithamova, D and Preston, AR (2014) CA1 subfield contributions to memory integration and inference. Hippocampus 24, 12481260.
Siegle, GJ, Steinhauer, SR, Thase, ME, Stenger, VA and Carter, CS (2002) Can't shake that feeling: event-related fMRI assessment of sustained amygdala activity in response to emotional information in depressed individuals. Biological Psychiatry 51, 693707.
Siegle, GJ, Carter, CS and Thase, ME (2006) Use of FMRI to predict recovery from unipolar depression with cognitive behavior therapy. The American Journal of Psychiatry 163, 735738.
Silvers, JA, Hubbard, AD, Biggs, E, Shu, J, Fertuck, E, Chaudhury, S, Grunebaum, MF, Weber, J, Kober, H, Chesin, M, Brodsky, BS, Koenigsberg, H, Ochsner, KN and Stanley, B (2016) Affective lability and difficulties with regulation are differentially associated with amygdala and prefrontal response in women with Borderline Personality Disorder. Psychiatry Research: Neuroimaging 254, 7482.
Simons, LE, Moulton, EA, Linnman, C, Carpino, E, Becerra, L and Borsook, D (2014) The human amygdala and pain: evidence from neuroimaging. Human Brain Mapping 35, 527538.
Stephanou, K, Davey, CG, Kerestes, R, Whittle, S and Harrison, BJ (2017) Hard to look on the bright side: neural correlates of impaired emotion regulation in depressed youth. Social Cognitive and Affective Neuroscience 12, 11381148.
Van Daele, T, Griffith, JW, Van den Bergh, O and Hermans, D (2014) Overgeneral autobiographical memory predicts changes in depression in a community sample. Cognition and Emotion 28, 13031312.
Williams, LM, Korgaonkar, MS, Song, YC, Paton, R, Eagles, S, Goldstein-Piekarski, A, Grieve, SM, Harris, AW, Usherwood, T and Etkin, A (2015) Amygdala reactivity to emotional faces in the prediction of general and medication-specific responses to antidepressant treatment in the randomized iSPOT-D trial. Neuropsychopharmacology 40, 23982408.
Woo, CW, Krishnan, A and Wager, TD (2014) Cluster-extent based thresholding in fMRI analyses: pitfalls and recommendations. NeuroImage 91, 412419.
Woolrich, M (2008) Robust group analysis using outlier inference. NeuroImage 41, 286301.
Worsley, KJ (2001) Functional MRI: an introduction to methods. Ch 14, In Statistical Analysis of Activation Images. (ed. Jezzard, P., Matthews, PM, Smith, SM), pp. 251270. Oxford University Press: New York.
Yesudas, EH and Lee, TM (2015) The role of cingulate cortex in vicarious pain. BioMed Research International 2015, 719615.
Zilverstand, A, Parvaz, MA and Goldstein, RZ (2017) Neuroimaging cognitive reappraisal in clinical populations to define neural targets for enhancing emotion regulation. A systematic review. NeuroImage 151, 105116.

Keywords

Neural predictors and effects of cognitive behavioral therapy for depression: the role of emotional reactivity and regulation

  • Harry Rubin-Falcone (a1) (a2), Jochen Weber (a3), Ronit Kishon (a1), Kevin Ochsner (a3), Lauren Delaparte (a4), Bruce Doré (a5), Sudha Raman (a1) (a2), Bryan T. Denny (a6), Maria A. Oquendo (a7), J. John Mann (a1) (a2) and Jeffrey M. Miller (a1) (a2)...

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