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Influence of electroconvulsive therapy on white matter structure in a diffusion tensor imaging study



Electroconvulsive therapy (ECT) is a fast-acting intervention for major depressive disorder. Previous studies indicated neurotrophic effects following ECT that might contribute to changes in white matter brain structure. We investigated the influence of ECT in a non-randomized prospective study focusing on white matter changes over time.


Twenty-nine severely depressed patients receiving ECT in addition to inpatient treatment, 69 severely depressed patients with inpatient treatment (NON-ECT) and 52 healthy controls (HC) took part in a non-randomized prospective study. Participants were scanned twice, approximately 6 weeks apart, using diffusion tensor imaging, applying tract-based spatial statistics. Additional correlational analyses were conducted in the ECT subsample to investigate the effects of seizure duration and therapeutic response.


Mean diffusivity (MD) increased after ECT in the right hemisphere, which was an ECT-group-specific effect. Seizure duration was associated with decreased fractional anisotropy (FA) following ECT. Longitudinal changes in ECT were not associated with therapy response. However, within the ECT group only, baseline FA was positively and MD negatively associated with post-ECT symptomatology.


Our data suggest that ECT changes white matter integrity, possibly reflecting increased permeability of the blood–brain barrier, resulting in disturbed communication of fibers. Further, baseline diffusion metrics were associated with therapy response. Coherent fiber structure could be a prerequisite for a generalized seizure and inhibitory brain signaling necessary to successfully inhibit increased seizure activity.


Corresponding author

Author for correspondence: Udo Dannlowski, E-mail:


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This is to indicate that the authors contributed equally to the present work and should therefore both be regarded as first/senior authors.



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Andrade, C and Bolwig, TG (2014) Electroconvulsive therapy, hypertensive surge, blood-brain barrier breach, and amnesia: exploring the evidence for a connection. Journal of ECT 30, 160164.
Berlim, MT, Fleck, MP and Turecki, G (2008) Current trends in the assessment and somatic treatment of resistant/refractory major depression: an overview. Annals of Medicine 40, 149159.
Bihan, DL (2003) Looking at the functional architecture of the brain with diffusion {MRI}. Nature Reviews Neuroscience 4, 469480.
Bullmore, ET, Suckling, J, Overmeyer, S, Rabe-Hesketh, S, Taylor, E and Brammer, MJ (1999) Global, voxel, and cluster tests, by theory and permutation, for a difference between two groups of structural MR images of the brain. IEEE Transactions on Medical Imaging 18, 3242.
Bumb, JM, Aksay, SS, Janke, C, Kranaster, L, Geisel, O, Gass, P, Hellweg, R and Sartorius, A (2015) Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients. European Archives of Psychiatry and Clinical Neuroscience 265, 227232.
De Vreede, IM, Burger, H and van Vliet, IM (2005) Prediction of response to ECT with routinely collected data in major depression. Journal of Affective Disorders 86, 323327.
Fink, M (2014) What was learned: studies by the consortium for research in ECT (CORE) 19972011. Acta Psychiatrica Scandinavica 129, 417426.
Folkerts, H (1996) The ictal electroencephalogram as a marker for the efficacy of electroconvulsive therapy. European Archives of Psychiatry and Clinical Neuroscience 246, 155164.
Ganzola, R, Nickson, T, Bastin, ME, Giles, S, Macdonald, A, Sussmann, J, McIntosh, AM, Whalley, HC and Duchesne, S (2017) Longitudinal differences in white matter integrity in youth at high familial risk for bipolar disorder. Bipolar Disorders 19, 158167.
Gardner, DM, Murphy, AL, O'Donnell, H, Centorrino, F and Baldessarini, RJ (2010) International consensus study of antipsychotic dosing. American Journal of Psychiatry 167, 686693.
Hamilton, M (1960) A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry 23, 5662.
Haq, AU, Sitzmann, AF, Goldman, ML, Maixner, DF and Mickey, BJ (2015) Response of depression to electroconvulsive therapy: a meta-analysis of clinical predictors. Journal of Clinical Psychiatry 76, 13741384.
Hellsten, J, West, MJ, Arvidsson, A, Ekstrand, J, Jansson, L, Wennström, M and Tingström, A (2005) Electroconvulsive seizures induce angiogenesis in adult rat hippocampus. Biological Psychiatry 58, 871878.
Hickie, I, Mason, C, Parker, G and Brodaty, H (1996) Prediction of ECT response: validation of a refined sign-based (CORE) system for defining melancholia. British Journal of Psychiatry 169, 6874.
Hoy, KE and Fitzgerald, PB (2010) Brain stimulation in psychiatry and its effects on cognition. Nature Reviews Neurology 6, 267275.
Jenkinson, M, Beckmann, C, Behrens, TE, Woolrich, MW and Smith, SM (2012) FSL. NeuroImage 62, 782790.
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR and Walters, EE (2005) Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593.
Kondratyev, A, Ved, R and Gale, K (2002) The effects of repeated minimal electroconvulsive shock exposure on levels of mRNA encoding fibroblast growth factor-2 and nerve growth factor in limbic regions. Neuroscience 114, 411416.
Kranaster, L, Plum, P, Hoyer, C, Sartorius, A and Ullrich, H (2013) Burst suppression: a more valid marker of postictal central inhibition? Journal of ECT 29, 2528.
Lyden, H, Espinoza, RT, Pirnia, T, Clark, K, Joshi, SH, Leaver, AM, Woods, RP and Narr, KL (2014) Electroconvulsive therapy mediates neuroplasticity of white matter microstructure in major depression. Nature Publishing Group Transl Psychiatry 4, e380.
Madsen, TM, Treschow, A, Bengzon, J, Bolwig, TG, Lindvall, O and Tingström, A (2000) Increased neurogenesis in a model of electroconvulsive therapy. Biological Psychiatry 47, 10431049.
Malberg, JE, Eisch, AJ, Nestler, EJ and Duman, RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. The Journal of Neuroscience 20, 91049110.
Minelli, A, Abate, M, Zampieri, E, Gainelli, G, Trabucchi, L, Segala, M, Sartori, R, Gennarelli, M, Conca, A and Bortolomasi, M (2016) Seizure adequacy markers and the prediction of electroconvulsive therapy response. Journal of ECT 32, 8892.
Mori, S, Wakana, S, Nagae-Poetscher, LM and van Zijl, PCM (2005) MRI atlas of human white matter. American Journal of Neuroradiology 27, 13841385.
Nickl-Jockschat, T, Palomero Gallagher, N, Kumar, V, Hoffstaedter, F, Brügmann, E, Habel, U, Eickhoff, SB and Grözinger, M (2016) Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy? Springer Berlin Heidelberg European Archives of Psychiatry and Clinical Neuroscience 266, 261267.
Nobuhara, K, Okugawa, G, Minami, T, Takase, K, Yoshida, T, Yagyu, T, Tajika, A, Sugimoto, T, Tamagaki, C, Ikeda, K, Sawada, S and Kinoshita, T (2004) Effects of electroconvulsive therapy on frontal white matter in late-life depression: a diffusion tensor imaging study. Neuropsychobiology 50, 4853.
Oltedal, L, Narr, KL, Abbott, C, Anand, A, Argyelan, M, Bartsch, H, Dannlowski, U, Dols, A, van Eijndhoven, P, Emsell, L, Erchinger, VJ, Espinoza, R, Hahn, T, Hanson, LG, Hellemann, G, Jorgensen, MB, Kessler, U, Oudega, ML, Paulson, OB, Redlich, R, Sienaert, P, Stek, ML, Tendolkar, I, Vandenbulcke, M, Oedegaard, KJ and Dale, AM (2018) Volume of the human hippocampus and clinical response following electroconvulsive therapy. Biological Psychiatry 84, 574581.
Ottosson, JO and Odeberg, H (2012) Evidence-based electroconvulsive therapy. Acta Psychiatrica Scandinavica 125, 177184.
Oudega, ML, van Exel, E, Stek, ML, Wattjes, MP, van der Flier, WM, Comijs, HC, Dols, A, Scheltens, P, Barkhof, F, Eikelenboom, P and van den Heuvel, OA (2014) The structure of the geriatric depressed brain and response to electroconvulsive therapy. Psychiatry Research – Neuroimaging 222, 19.
Pekar, JJ, van Zijl, PCM, Reich, DS, Zhang, J, Calabresi, PA, Wakana, S, Mori, S, Li, X, Hua, K and Jiang, H (2007) Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification. NeuroImage 39, 336347.
Redlich, R, Almeida, JRC, Grotegerd, D, Opel, N, Kugel, H, Heindel, W, Arolt, V, Phillips, ML and Dannlowski, U (2014) Brain morphometric biomarkers distinguishing unipolar and bipolar depression: a voxel-based morphometry-pattern classification approach. JAMA Psychiatry 71, 12221230.
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 and Dannlowski, U (2016) Prediction of individual response to electroconvulsive therapy via machine learning on structural magnetic resonance imaging data. JAMA Psychiatry 73, 557564.
Repple, J, Meinert, S, Grotegerd, D, Kugel, H, Redlich, R, Dohm, K, Zaremba, D, Opel, N, Buerger, C, Förster, K, Nick, T, Arolt, V, Heindel, W, Deppe, M and Dannlowski, U (2017) A voxel-based diffusion tensor imaging study in unipolar and bipolar depression. Bipolar Disorders 19, 2331.
Sackeim, HA (1999) The anticonvulsant hypothesis of the mechanisms of action of ECT: current status. The Journal of ECT 15, 526.
Sartorius, A, Demirakca, T, Böhringer, A, Clemm von Hohenberg, C, Aksay, SS, Bumb, JM, Kranaster, L, Nickl-Jockschat, T, Grözinger, M, Thomann, PA, Wolf, RC, Zwanzger, P, Dannlowski, U, Redlich, R, Zavorotnyy, M, Zöllner, R, Methfessel, I, Besse, M, Zilles, D and Ende, G (2019) Electroconvulsive therapy induced gray matter increase is not necessarily correlated with clinical data in depressed patients. Brain Stimulation 12, 335343.
Semkovska, M and McLoughlin, DM (2010) Objective cognitive performance associated with electroconvulsive therapy for depression: a systematic review and meta-analysis. Biological Psychiatry 68, 568577.
Shah, AJ, Wadoo, O and Latoo, J (2013) Electroconvulsive therapy (ECT): important parameters which influence its effectiveness. British Journal of Medical Practitioners 6(4).
Smith, SM and Nichols, TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. NeuroImage 44, 8398.
Smith, SM, Jenkinson, M, Johansen-Berg, H, Rueckert, D, Nichols, TE, Mackay, CE, Watkins, KE, Ciccarelli, O, Cader, MZ, Matthews, PM and Behrens, TEJ (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. NeuroImage 31, 14871505.
ten Doesschate, F, van Eijndhoven, P, Tendolkar, I, van Wingen, Ga and van Waarde, JA (2014) Pre-treatment amygdala volume predicts electroconvulsive therapy response. Frontiers in Psychiatry 5, 17.
Tor, PC, Bautovich, A, Wang, MJ, Martin, D, Harvey, SB and Loo, C (2015) A systematic review and meta-analysis of brief versus ultrabrief right unilateral electroconvulsive therapy for depression. Journal of Clinical Psychiatry 76, e1092e1098.
UK ECT Review Group (2003) Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. The Lancet 361, 799808.
Weiner, RD and Reti, IM (2017) Key updates in the clinical application of electroconvulsive therapy. International Review of Psychiatry 29, 5462.
Wennström, M, Hellsten, J, Ekstrand, J, Lindgren, H and Tingström, A (2006) Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures. Biological Psychiatry 59, 178186.
Winkler, AM, Ridgway, GR, Webster, MA, Smith, SM and Nichols, TE (2014) Permutation inference for the general linear model. NeuroImage 92, 381397.
Wittchen, H, Zaudig, M and Fydrich, T (1997) Strukturiertes Klinisches Interview für DSM-IV, Hogrefe. Germany: Göttingen.
Yrondi, A, Sporer, M, Péran, P, Schmitt, L, Arbus, C and Sauvaget, A (2017) Electroconvulsive therapy, depression, the immune system and inflammation: a systematic review. Brain Stimulation.


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