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Effects of electroconvulsive therapy on amygdala function in major depression – a longitudinal functional magnetic resonance imaging study

  • R. Redlich (a1), C. Bürger (a1), K. Dohm (a1), D. Grotegerd (a1), N. Opel (a1), D. Zaremba (a1), S. Meinert (a1), K. Förster (a1), J. Repple (a1), R. Schnelle (a1), C. Wagenknecht (a1), M. Zavorotnyy (a2), W. Heindel (a3), H. Kugel (a3), M. Gerbaulet (a1), J. Alferink (a1) (a4), V. Arolt (a1), P. Zwanzger (a1) (a5) (a6) and U. Dannlowski (a1)...



Electroconvulsive therapy (ECT) is one of the most effective treatments for severe depression. However, little is known regarding brain functional processes mediating ECT effects.


In a non-randomized prospective study, functional magnetic resonance imaging data during the automatic processing of subliminally presented emotional faces were obtained twice, about 6 weeks apart, in patients with major depressive disorder (MDD) before and after treatment with ECT (ECT, n = 24). Additionally, a control sample of MDD patients treated solely with pharmacotherapy (MED, n = 23) and a healthy control sample (HC, n = 22) were obtained.


Before therapy, both patient groups equally showed elevated amygdala reactivity to sad faces compared with HC. After treatment, a decrease in amygdala activity to negative stimuli was discerned in both patient samples indicating a normalization of amygdala function, suggesting mechanisms potentially unspecific for ECT. Moreover, a decrease in amygdala activity to sad faces was associated with symptomatic improvements in the ECT sample (r spearman = −0.48, p = 0.044), and by tendency also for the MED sample (r spearman = −0.38, p = 0.098). However, we did not find any significant association between pre-treatment amygdala function to emotional stimuli and individual symptom improvement, neither for the ECT sample, nor for the MED sample.


In sum, the present study provides first results regarding functional changes in emotion processing due to ECT treatment using a longitudinal design, thus validating and extending our knowledge gained from previous treatment studies. A limitation was that ECT patients received concurrent medication treatment.


Corresponding author

* Address for correspondence: R. Redlich, Ph.D., Department of Psychiatry, University of Münster, Albert-Schweitzer-Campus 1, A9, 48149 Münster, Germany. (Email:


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Abbott, CC, Jones, T, Lemke, NT, Gallegos, P, McClintock, SM, Mayer, AR, Bustillo, J, Calhoun, VD (2014). Hippocampal structural and functional changes associated with electroconvulsive therapy response. Translational Psychiatry 4, e483.
Anand, A, Li, Y, Wang, Y, Gardner, K, Lowe, MJ (2007). Reciprocal effects of antidepressant treatment on activity and connectivity of the mood regulating circuit: an fMRI study. Journal of Neuropsychiatry and Clinical Neurosciences 19, 274282.
Argyelan, M, Lencz, T, Kaliora, S, Sarpal, DK, Weissman, N, Kingsley, PB, Malhotra, AK, Petrides, G (2016). Subgenual cingulate cortical activity predicts the efficacy of electroconvulsive therapy. Translational Psychiatry 6, e789.
Bogod, NM, Sinden, M, Woo, C, Defreitas, VG, Torres, IJ, Howard, AK, Ilcewicz-Klimek, MI, Honey, CR, Yatham, LN, Lam, RW (2014). Long-term neuropsychological safety of subgenual cingulate gyrus deep brain stimulation for treatment-resistant depression. Journal of Neuropsychiatry and Clinical Neurosciences 26, 126133.
Bouckaert, F, De Winter, FL, Emsell, L, Dols, A, Rhebergen, D, Wampers, M, Sunaert, S, Stek, ML, Sienaert, P, Vandenbulcke, M (2016). Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study. Journal of Psychiatry and Neuroscience 41, 105114.
Canli, T, Cooney, RE, Goldin, P, Shah, M, Sivers, H, Thomason, ME, Whitfield-Gabrieli, S, Gabrieli, JDE, Gotlib, IH (2005). Amygdala reactivity to emotional faces predicts improvement in major depression. Neuroreport 16, 12671270.
Dannlowski, U, Grabe, HJ, Wittfeld, K, Klaus, J, Konrad, C, Grotegerd, D, Redlich, R, Suslow, T, Opel, N, Ohrmann, P, Bauer, J, Zwanzger, P, Laeger, I, Hohoff, C, Arolt, V, Heindel, W, Deppe, M, Domschke, K, Hegenscheid, K, Völzke, H, Stacey, D, Meyer Zu Schwabedissen, H, Kugel, H, Baune, BT (2015). Multimodal imaging of a tescalcin (TESC)-regulating polymorphism (rs7294919)-specific effects on hippocampal gray matter structure. Molecular Psychiatry 20, 398404.
Dannlowski, U, Konrad, C, Kugel, H, Zwitserlood, P, Domschke, K, Schöning, S, Ohrmann, P, Bauer, J, Pyka, M, Hohoff, C, Zhang, W, Baune, BT, Heindel, W, Arolt, V, Suslow, T (2010). Emotion specific modulation of automatic amygdala responses by 5-HTTLPR genotype. NeuroImage 53, 893898.
Dannlowski, U, Kugel, H, Huber, F, Stuhrmann, A, Redlich, R, Grotegerd, D, Dohm, K, Sehlmeyer, C, Konrad, C, Baune, BT, Arolt, V, Heindel, W, Zwitserlood, P, Suslow, T (2013). Childhood maltreatment is associated with an automatic negative emotion processing bias in the amygdala. Human Brain Mapping 34, 28992909.
De Raedt, R, Leyman, L, Baeken, C, Van Schuerbeek, P, Luypaert, R, Vanderhasselt, M-A, Dannlowski, U (2010). Neurocognitive effects of HF-rTMS over the dorsolateral prefrontal cortex on the attentional processing of emotional information in healthy women: an event-related fMRI study. Biological Psychology 85, 487495.
Dukart, J, Regen, F, Kherif, F, Colla, M, Bajbouj, M, Heuser, I (2014). Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders. PNAS 111, 11561161.
Ekman, P, Friesen, WV (1976). Pictures of Facial Affect. Consulting Psychologists Press: Palo Alto, CA.
Forman, SD, Cohen, JD, Fitzgerald, M, Eddy, WF, Mintun, MA, Noll, DC (1995). Improved assessment of significant activation in functional magnetic resonance imaging (fMRI): use of a cluster-size threshold. Magnetic Resonance Medicine 33, 636647.
Fu, CHY, Williams, SCR, Cleare, AJ, Brammer, MJ, Walsh, ND, Kim, J, Andrew, C, Pich, EM, Williams, PM, Reed, LJ, Mitterschiffthaler, MT, Suckling, J, Bullmore, ET (2004). Attenuation of the neural response to sad faces in major depression by antidepressant treatment: a prospective, event-related functional magnetic resonance imaging study. Archives of General Psychiatry 61, 877889.
Groenewold, NA, Opmeer, EM, de Jonge, P, Aleman, A, Costafreda, SG (2013). Emotional valence modulates brain functional abnormalities in depression: evidence from a meta-analysis of fMRI studies. Neuroscience and Biobehavioral Reviews 37, 152163.
Grotegerd, D, Stuhrmann, A, Kugel, H, Schmidt, S, Redlich, R, Zwanzger, P, Rauch, AV, Heindel, W, Zwitserlood, P, Arolt, V, Suslow, T, Dannlowski, U (2014). Amygdala excitability to subliminally presented emotional faces distinguishes unipolar and bipolar depression – an fMRI and pattern classification study. Human Brain Mapping 35, 29953007.
Hamilton, JP, Etkin, A, Furman, DJ, Lemus, MG, Johnson, RF, Gotlib, IH (2012). Functional neuroimaging of major depressive disorder: a meta-analysis and new integration of base line activation and neural response data. American Journal of Psychiatry 169, 693703.
Hamilton, M (1960). A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5663.
Harmer, CJ, Goodwin, GM, Cowen, PJ (2009). Why do antidepressants take so long to work? A cognitive neuropsychological model of antidepressant drug action. British Journal of Psychiatry: the Journal of Mental Science 195, 102108.
Hautzinger, M, Bailer, M, Worall, H, Keller, F (1994). Beck Depressions-Inventar (BDI). Testhandbuch. Hans Huber: Bern.
Joormann, J, Cooney, RE, Henry, ML, Gotlib, IH (2011). Neural correlates of automatic mood regulation in girls at high risk for depression. Journal of Abnormal Psychology 121, 6172.
Jorgensen, A, Magnusson, P, Hanson, LG, Kirkegaard, T, Benveniste, H, Lee, H, Svarer, C, Mikkelsen, JD, Fink-Jensen, A, Knudsen, GM, Paulson, OB, Bolwig, TG, Jorgensen, MB (2015). Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. Acta Psychiatrica Scandinavica 133, 154164.
Joshi, SH, Espinoza, RT, Pirnia, T, Shi, J, Wang, Y, Ayers, B, Leaver, A, Woods, RP, Narr, KL (2016). Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in major depression. Biological Psychiatry 79, 282292.
Kho, KH, van Vreeswijk, MF, Simpson, S, Zwinderman, AH (2003). A meta-analysis of electroconvulsive therapy efficacy in depression. Journal of ECT 19, 139147.
Kuhs, H (1995). [Stages of treatment resistance in depressive disorders, defined after somatotherapeutic methods]. Der Nervenarzt 66, 561567.
Leaver, AM, Espinoza, R, Pirnia, T, Joshi, SH, Woods, RP, Narr, KL (2016). Modulation of intrinsic brain activity by electroconvulsive therapy in major depression. Biological Psychiatry 1, 7786.
Liu, Y, Du, L, Li, Y, Liu, H, Zhao, W, Liu, D, Zeng, J, Li, X, Fu, Y, Qiu, H, Li, X, Qiu, T, Hu, H, Meng, H, Luo, Q (2015). Antidepressant effects of electroconvulsive therapy correlate with subgenual anterior cingulate activity and connectivity in depression. Medicine 94, e2033.
Nickl-Jockschat, T, Palomero Gallagher, N, Kumar, V, Hoffstaedter, F, Brügmann, E, Habel, U, Eickhoff, SB, Grözinger, M (2016). Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy? European Archives of Psychiatry and Clinical Neuroscience 266, 261267.
Njau, S, Joshi, SH, Espinoza, R, Leaver, AM, Vasavada, M, Marquina, A, Woods, RP, Narr, KL (2016). Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. Journal of Psychiatry and Neuroscience 41, 150177.
Norbury, R, Taylor, MJ, Selvaraj, S, Murphy, SE, Harmer, CJ, Cowen, PJ (2009). Short-term antidepressant treatment modulates amygdala response to happy faces. Psychopharmacology 206, 197204.
Opel, N, Redlich, R, Grotegerd, D, Dohm, K, Haupenthal, C, Heindel, W, Kugel, H, Arolt, V, Dannlowski, U (2015). Enhanced neural responsiveness to reward associated with obesity in the absence of food-related stimuli. Human Brain Mapping 36, 23302337.
Redlich, R, Almeida, JRC, Grotegerd, D, Opel, N, Kugel, H, Heindel, W, Arolt, V, Phillips, ML, Dannlowski, U (2014). Brain morphometric biomarkers distinguishing unipolar and bipolar depression: a voxel-based morphometry-pattern classification approach. JAMA Psychiatry 71, 12221230.
Redlich, R, Dohm, K, Grotegerd, D, Opel, N, Zwitserlood, P, Heindel, W, Arolt, V, Kugel, H, Dannlowski, U (2015 a). Reward processing in unipolar and bipolar depression: a functional MRI study. Neuropsychopharmacology 40, 26232631.
Redlich, R, Grotegerd, D, Opel, N, Kaufmann, C, Zwitserlood, P, Kugel, H, Heindel, W, Donges, US, Suslow, T, Arolt, V, Dannlowski, U (2015 b). Are you gonna leave me? Separation anxiety is associated with increased amygdala responsiveness and volume. Social Cognitive and Affective Neuroscience 10, 278284.
Redlich, R, Opel, N, Grotegerd, D, Dohm, K, Zaremba, D, Bürger, C, Münker, S, Mühlmann, L, Wahl, P, Heindel, W, Arolt, V, Alferink, J, Zwanzger, P, Zavorotnyy, M, Kugel, H, Dannlowski, U (2016). Prediction of individual response to electroconvulsive therapy via machine learning on structural magnetic resonance imaging data. JAMA Psychiatry 73, 557564.
Redlich, R, Stacey, D, Opel, N, Grotegerd, D, Dohm, K, Kugel, H, Heindel, W, Arolt, V, Baune, BT, Dannlowski, U (2015 c). Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli. Psychoneuroendocrinology 62, 166173.
Salvadore, G, Cornwell, BR, Colon-Rosario, V, Coppola, R, Grillon, C, Zarate, CA, Manji, HK (2009). Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biological Psychiatry 65, 289295.
Sheline, YI, Barch, DM, Donnelly, JM, Ollinger, JM, Snyder, AZ, Mintun, MA (2001). Increased amygdala response to masked emotional faces in depressed subjects resolves with antidepressant treatment: an fMRI study. Biological Psychiatry 50, 651658.
Siegle, GJ, Carter, CS, Thase, ME (2006). Use of fMRI to predict recovery from unipolar depression with cognitive behavior therapy. American Journal of Psychiatry 163, 735738.
Siegle, GJ, Thompson, WK, Carter, CS, Steinhauer, SR, Thase, ME (2007). Increased amygdala and decreased dorsolateral prefrontal BOLD responses in unipolar depression: related and independent features. Biological Psychiatry 61, 198209.
Stuhrmann, A, Dohm, K, Kugel, H, Zwanzger, P, Redlich, R, Grotegerd, D, Rauch, AV, Arolt, V, Heindel, W, Suslow, T, Zwitserlood, P, Dannlowski, U (2013). Mood-congruent amygdala responses to subliminally presented facial expressions in major depression: associations with anhedonia. Journal of Psychiatry and Neuroscience 37, 249258.
Suslow, T, Konrad, C, Kugel, H, Rumstadt, D, Zwitserlood, P, Schöning, S, Ohrmann, P, Bauer, J, Pyka, M, Kersting, A, Arolt, V, Heindel, W, Dannlowski, U (2010). Automatic mood-congruent amygdala responses to masked facial expressions in major depression. Biological Psychiatry 67, 155160.
Suslow, T, Kugel, H, Ohrmann, P, Stuhrmann, A, Grotegerd, D, Redlich, R, Bauer, J, Dannlowski, U (2013). Neural correlates of affective priming effects based on masked facial emotion: an fMRI study. Psychiatry Research 211, 239245.
Taghva, AS, Malone, DA, Rezai, AR (2013). Deep brain stimulation for treatment-resistant depression. World Neurosurgery 80, S27.e17S27.e24.
Tendolkar, I, van Beek, M, van Oostrom, I, Mulder, M, Janzing, J, Voshaar, RO, van Eijndhoven, P (2013). Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression: a longitudinal pilot study. Psychiatry Research 214, 197203.
Tzourio-Mazoyer, N, Landeau, B, Papathanassiou, D, Crivello, F, Etard, O, Delcroix, N, Mazoyer, B, Joliot, M (2002). Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. NeuroImage 15, 273289.
van Harmelen, A-L, van Tol, M-J, Demenescu, LR, van der Wee, NJA, Veltman, DJ, Aleman, A, van Buchem, MA, Spinhoven, P, Penninx, B, Elzinga, BM (2013). Enhanced amygdala reactivity to emotional faces in adults reporting childhood emotional maltreatment. Social Cognitive and Affective Neuroscience 8, 362369.
van Waarde, JA, Scholte, HS, van Oudheusden, LJB, Verwey, B, Denys, D, van Wingen, GA (2015). A functional MRI marker may predict the outcome of electroconvulsive therapy in severe and treatment-resistant depression. Molecular Psychiatry 20, 609614.
Victor, TA, Furey, ML, Fromm, SJ, Ohman, A, Drevets, WC (2010). Relationship between amygdala responses to masked faces and mood state and treatment in major depressive disorder. Archives of General Psychiatry 67, 11281138.
Williams, LM, Korgaonkar, MS, Song, YC, Paton, R, Eagles, S, Goldstein-Piekarski, A, Grieve, SM, Harris, AW, Usherwood, T, 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.
Wittchen, H-U, Wunderlich, U, Gruschwitz, S, Zaudig, M (1997). Strukturiertes Klinisches Interview für DSM-IV. Hogrefe: Goettingen.



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