Skip to main content Accessibility help

Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis

  • Akihiro Takamiya (a1), Jun Ku Chung (a2), Kuo-ching Liang (a3), Ariel Graff-Guerrero (a4), Masaru Mimura (a3) and Taishiro Kishimoto (a5)...



Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, although the underlying mechanisms remain unclear. Animal studies have shown that electroconvulsive shock induced neuroplastic changes in the hippocampus.


To summarise volumetric magnetic resonance imaging studies investigating the effects of ECT on limbic brain structures.


A systematic review and meta-analysis was conducted to assess volumetric changes of each side of the hippocampus and amygdala before and after ECT. Standardised mean difference (SMD) was calculated.


A total of 8 studies (n = 193) were selected for our analyses. Both right and left hippocampal and amygdala volumes increased after ECT. Meta-regression analyses revealed that age, percentage of those responding and percentage of those in remission were negatively associated with volume increases in the left hippocampus.


ECT increased brain volume in the limbic structures. The clinical relevance of volume increase needs further investigation.

Declaration of interest


  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis
      Available formats


Corresponding author

Correspondence: Dr Taishiro Kishimoto, Keio University School of Medicine, Department of Neuropsychiatry, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Email:


Hide All
1.Carney, S, Cowen, P, Geddes, J, Goodwin, G, Rogers, R, Dearness, K, et al. Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet 2003; 361: 799808.
2.Pagnin, D, de Queiroz, V, Pini, S, Cassano, GB. Efficacy of ECT in depression: a meta-analytic review. J ECT 2004; 20: 1320.
3.Kellner, CH, Kaicher, DC, Banerjee, H, Knapp, RG, Shapiro, RJ, Briggs, MC, et al. Depression severity in electroconvulsive therapy (ECT) versus pharmacotherapy trials. J ECT 2015; 31: 31–3.
4.Husain, MM, Rush, AJ, Fink, M, Knapp, R, Petrides, G, Rummans, T, et al. Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a consortium for research in ECT (CORE) report. J Clin Psychiatry 2004; 65: 485–91.
5.Spaans, HP, Sienaert, P, Bouckaert, F, van den Berg, JF, Verwijk, E, Kho, KH, et al. Speed of remission in elderly patients with depression: electroconvulsive therapy v. medication. Br J Psychiatry 2015; 206: 6771.
6.Kellner, CH, Fink, M, Knapp, R, Petrides, G, Husain, M, Rummans, T, et al. Relief of expressed suicidal intent by ECT: a consortium for research in ECT study. Am J Psychiatry 2005; 162: 977–82.
7.Kellner, CH, Greenberg, RM, Murrough, JW, Bryson, EO, Briggs, MC, Pasculli, RM. ECT in treatment-resistant depression. Am J Psychiatry 2012; 169: 1238–44.
8.Madsen, TM, Treschow, A, Bengzon, J, Bolwig, TG, Lindvall, O, Tingstrom, A. Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 2000; 47: 1043–9.
9.Malberg, JE, Eisch, AJ, Nestler, EJ, Duman, RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000; 20: 9104–10.
10.Perera, TD, Coplan, JD, Lisanby, SH, Lipira, CM, Arif, M, Carpio, C, et al. Antidepressant-induced neurogenesis in the hippocampus of adult nonhuman primates. J Neurosci 2007; 27: 4894–901.
11.Warner-Schmidt, JL, Duman, RS. VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci USA 2007; 104: 4647–52.
12.Nordanskog, P, Dahlstrand, U, Larsson, MR, Larsson, EM, Knutsson, L, Johanson, A. Increase in hippocampal volume after electroconvulsive therapy in patients with depression: a volumetric magnetic resonance imaging study. J ECT 2010; 26: 6267.
13.Abbott, CC, Gallegos, P, Rediske, N, Lemke, NT, Quinn, DK. A review of longitudinal electroconvulsive therapy: neuroimaging investigations. J Geriatr Psychiatry Neurol 2014; 27: 3346.
14.Bolwig, TG. Neuroimaging and electroconvulsive therapy: a review. J ECT 2014; 30: 138–42.
15.Zhuo, C, Yu, C. Functional neuroimaging changes subsequent to electroconvulsive therapy in unipolar depression: a review of the literature. J ECT 2014; 30: 265–74.
16.Yrondi, A, Peran, P, Sauvaget, A, Schmitt, L, Arbus, C. Structural–functional brain changes in depressed patients during and after electroconvulsive therapy. Acta Neuropsychiatr 2016; 23: 112.
17.Wilkinson, ST, Sanacora, G, Bloch, MH. Hippocampal volume changes following electroconvulsive therapy: a systematic review and meta-analysis. Biol Psychiatry Cogn Neurosci Neuroimaging 2017; 2: 327–35.
18.Bouckaert, F, Dols, A, Emsell, L, De Winter, FL, Vansteelandt, K, Claes, L, et al. Relationship between hippocampal volume, serum BDNF and depression severity following electroconvulsive therapy in late-life depression. Neuropsychopharmacol 2016; 41: 2741–8.
19.Stroup, DF, Berlin, JA, Morton, SC, Olkin, I, Williamson, GD, Rennie, D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283: 2008–12.
20.Wells, G, Shea, B, O'Connell, D, Peterson, J, Welch, V, Losos, M, et al. The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Non-randomised Studies in Meta-analysis. Ottawa Health Research Institute, 2004.
21.Egger, M, Davey Smith, G, Schneider, M, Minder, C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–34.
22.Duval, S, Tweedie, R. A nonparametric ‘trim and fill’ method of accounting for publication bias in meta-analysis. J Am Stat Assoc 2000; 95: 8998.
23.Coffey, CE, Weiner, RD, Djang, WT, Figiel, GS, Soady, SAR, Patterson, LJ, et al. Brain anatomic effects of electroconvulsive therapy. Arch Gen Psychiatry 1991; 48: 1013–21.
24.Nordanskog, P, Larsson, MR, Larsson, EM, Johanson, A. Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression. Acta Psychiatr Scand 2014; 129: 303–11.
25.Tendolkar, I, van Beek, M, van Oostrom, I, Mulder, M, Janzing, J, Voshaar, RO, et al. Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression: a longitudinal pilot study. Psychiatry Res Neuroimaging 2013; 214: 197203.
26.Dukart, J, Regen, F, Kherif, F, Colla, M, Bajbouj, M, Heuser, I, et al. Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders. Proc Natl Acad Sci USA 2014; 111: 1156–61.
27.Abbott, CC, Jones, T, Lemke, NT, Gallegos, P, McClintock, SM, Mayer, AR, et al. Hippocampal structural and functional changes associated with electroconvulsive therapy response. Transl Psychiatry 2014; 4: e483.
28.Jorgensen, A, Magnusson, P, Hanson, LG, Kirkegaard, T, Benveniste, H, Lee, H, et al. Regional brain volumes, diffusivity, and metabolite changes after electroconvulsive therapy for severe depression. Acta Psychiatr Scand 2016; 133: 154–64.
29.Ota, M, Noda, T, Sato, N, Okazaki, M, Ishikawa, M, Hattori, K, et al. Effect of electroconvulsive therapy on gray matter volume in major depressive disorder. J Affect Disord 2015; 186: 186–91.
30.Bouckaert, F, De Winter, FL, Emsell, L, Dols, A, Rhebergen, D, Wampers, M, et al. Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study. J Psychiatry Neurosci 2016; 41: 105–14.
31.Nickl-Jockschat, T, Palomero Gallagher, N, Kumar, V, Hoffstaedter, F, Brugmann, E, Habel, U, et al. Are morphological changes necessary to mediate the therapeutic effects of electroconvulsive therapy? Eur Arch Psychiatry Clin Neurosci 2016; 266: 261–7.
32.Joshi, SH, Espinoza, RT, Pirnia, T, Shi, J, Wang, Y, Ayers, B, et al. Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in major depression. Biol Psychiatry 2016; 79: 282–92.
33.Sartorius, A, Demirakca, T, Bohringer, A, Clemm von Hohenberg, C, Aksay, SS, Bumb, JM, et al. Electroconvulsive therapy increases temporal gray matter volume and cortical thickness. Eur Neuropsychopharmacol 2016; 26: 506–17.
34.Redlich, R, Opel, N, Grotegerd, D, Dohm, K, Zaremba, D, Burger, C, et al. Prediction of individual response to electroconvulsive therapy via machine learning on structural magnetic resonance imaging data. JAMA Psychiatry 2016; 73: 557–64.
35.Wolf, RC, Nolte, HM, Hirjak, D, Hofer, S, Seidl, U, Depping, MS, et al. Structural network changes in patients with major depression and schizophrenia treated with electroconvulsive therapy. Eur Neuropsychopharmacol 2016; 26: 1465–74.
36.Qiu, H, Li, X, Zhao, W, Du, L, Huang, P, Fu, Y, et al. Electroconvulsive therapy-induced brain structural and functional changes in major depressive disorders: a longitudinal study. Med Sci Monit 2016; 22: 4577–86.
37.Thomann, PA, Wolf, RC, Nolte, HM, Hirjak, D, Hofer, S, Seidl, U, et al. Neuromodulation in response to electroconvulsive therapy in schizophrenia and major depression. Brain Stimul 2017; 10: 637–44.
38.Cano, M, Martinez-Zalacain, I, Bernabeu-Sanz, A, Contreras-Rodriguez, O, Hernandez-Ribas, R, Via, E, et al. Brain volumetric and metabolic correlates of electroconvulsive therapy for treatment-resistant depression: a longitudinal neuroimaging study. Transl Psychiatry 2017; 7: e1023.
39.Kunigiri, G, Jayakumar, PN, Janakiramaiah, N, Gangadhar, BN. MRI T (2) relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy. Indian J Psychiatry 2007; 49: 195199.
40.Szabo, K, Hirsch, JG, Krause, M, Ende, G, Henn, FA, Sartorius, A, et al. Diffusion weighted MRI in the early phase after electroconvulsive therapy. Neurol Res 2007; 29: 256–9.
41.Franklin, TR, Wang, Z, Shin, J, Jagannathan, K, Suh, JJ, Detre, JA, et al. A VBM study demonstrating ‘apparent’ effects of a single dose of medication on T1-weighted MRIs. Brain Struct Funct 2013; 218: 97104.
42.Zatorre, RJ, Fields, RD, Johansen-Berg, H. Plasticity in gray and white: neuroimaging changes in brain structure during learning. Nat Neurosci 2012; 15: 528–36.
43.Santarelli, L, Saxe, M, Gross, C, Surget, A, Battaglia, F, Dulawa, S, et al. Requirement of hippocampal effects of antidepressants. Science 2011; 805: 805–9.
44.Perera, TD, Dwork, AJ, Keegan, KA, Thirumangalakudi, L, Lipira, CM, Joyce, N, et al. Necessity of hippocampal neurogenesis for the therapeutic action of antidepressants in adult nonhuman primates. PLoS One 2011; 6: e176000.
45.Eriksson, PS, Perfilieva, E, Bjork Eriksson, T, Alborn, AM, Nordborg, C, Peterson, DA, et al. Neurogenesis in the adult human hippocampus. Nat Med 1998; 4: 1313–7.
46.Spalding, KL, Bergmann, O, Alkass, K, Bernard, S, Salehpour, M, Huttner, HB, et al. Dynamics of hippocampal neurogenesis in adult humans. Cell 2013; 153: 1219–27.
47.Wennstrom, M, Hellsten, J, Ekdahl, CT, Tingstrom, A. Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat hippocampus. Biol Psychiatry 2003; 54: 1015–24.
48.Wennstrom, M, Hellsten, J, Ekstrand, J, Lindgren, H, Tingstrom, A. Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures. Biol Psychiatry 2006; 59: 178–86.
49.Kaae, SS, Chen, F, Wegener, G, Madsen, TM, Nyengaard, JR. Quantitative hippocampal structural changes following electroconvulsive seizure treatment in a rat model of depression. Synapse 2012; 66: 667–76.
50.Jansson, L, Wennstrom, M, Johanson, A, Tingstrom, A. Glial cell activation in response to electroconvulsive seizures. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 1119–28.
51.Dou, CL, Levine, JM. Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan. J Neurosci 1994; 14: 7616–28.
52.Bolwig, TG, Jorgen, OS. Synaptic proteins after electroconvulsive stimulation: reversibility and regional differences in the brain. Acta Psychiatr Scand 1980; 62: 486–93.
53.Chen, F, Madsen, TM, Wegener, G, Nyengaard, JR. Repeated electroconvulsive seizures increase the total number of synapses in adult male rat hippocampus. Eur Neuropsychopharmacol 2009; 19: 329–38.
54.Zhao, C, Warner-Schmidt, J, Duman, RS, Gage, FH. Electroconvulsive seizure promotes spine maturation in newborn dentate granule cells in adult rat. Dev Neurobiol 2012; 72: 937–42.
55.Hellsten, J, West, MJ, Arvidsson, A, Ekstrand, J, Jansson, L, Wennstrom, M, et al. Electroconvulsive seizures induce angiogenesis in adult rat hippocampus. Biol Psychiatry 2005; 58: 871–8.
56.Takano, H, Motohashi, N, Uema, T, Ogawa, K, Ohnishi, T, Nishikawa, M, et al. Changes in regional cerebral blood flow during acute electroconvulsive therapy in patients with depression: positron emission tomographic study. Br J Psychiatry 2007; 190: 63–8.
57.McCormick, LM, Boles Ponto, LL, Pierson, RK, Johnson, HJ, Magnotta, V, Brumm, MC. Metabolic correlates of antidepressant and antipsychotic response in patients with psychotic depression undergoing electroconvulsive therapy. J ECT 2007; 23: 265–73.
58.Suwa, T, Namiki, C, Takaya, S, Oshita, A, Ishizu, K, Fukuyama, H, et al. Corticolimbic balance shift of regional glucose metabolism in depressed patients treated with ECT. J Affect Disord 2012; 136: 1039–46.
59.Reininghaus, EZ, Reininghaus, B, Ille, R, Fitz, W, Lassnig, RM, Ebner, C, et al. Clinical effects of electroconvulsive therapy in severe depression and concomitant changes in cerebral glucose metabolism – an exploratory study. J Affect Disord 2012; 146: 290–4.
60.Bowley, MP, Drevets, WC, Ongur, D, Price, JL. Low glial numbers in the amygdala in major depressive disorder. Biol Psychiatry 2002; 52: 404–12.
61.Hamidi, M, Drevets, WC, Price, JL. Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes. Biol Psychiatry 2004; 55: 563–9.
62.Wennström, M, Hellsten, J, Tingstrom, A. Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat amygdala. Biol Psychiatry 2004; 55: 464–71.
63.Ongur, D, Drevets, WC, Price, JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998; 95: 13290–5.
64.Rotheneichner, P, Lange, S, O'Sullivan, A, Marschallinger, J, Zaunmair, P, Geretsegger, C, et al. Hippocampal neurogenesis and antidepressive therapy: shocking relations. Neural Plast 2014; 2014: 723915.
65.Czeh, B, Lucassen, PJ. What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated? Eur Arch Psychiatry Clin Neurosci 2007; 257: 250–60.
66.Shan, ZY, Liu, JZ, Sahgal, V, Wang, B, Yue, GH. Selective atrophy of left hemisphere and frontal lobe of the brain in old men. J Gerontol A Biol Sci Med Sci 2005; 60: 165–74.
67.Boldrini, M, Santiago, AN, Hen, R, Dwork, AJ, Rosoklija, GB, Tamir, H, et al. Hippocampal granule neuron number and dentate gyrus volume in antidepressant-treated and untreated major depression. Neuropsychopharmacology 2013; 38: 1068–77.
68.Malykhin, NV, Carter, R, Seres, P, Coupland, NJ. Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment. J Psychiatry Neurosci 2010; 35: 337–43.
69.Frodl, T, Jager, M, Smajstrlova, I, Born, C, Bottlender, R, Palladino, T, et al. Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. J Psychiatry Neurosci 2008; 33: 423–30.
70.Arnone, D, McKie, S, Elliott, R, Juhasz, G, Thomas, EJ, Downey, D, et al. State-dependent changes in hippocampal grey matter in depression. Mol Psychiatry 2013; 18: 1265–72.
71.Bodnar, M, Malla, AK, Makowski, C, Chakravarty, MM, Joober, R, Lepage, M. The effect of second-generation antipsychotics on hippocampal volume in first episode of psychosis: longitudinal study. BJPsych Open 2016; 2: 139–46.
72.Germana, C, Kempton, MJ, Sarnicola, A, Christodoulou, T, Haldane, M, Hadjulis, M, et al. The effects of lithium and anticonvulsants on brain structure in bipolar disorder. Acta Psychiatr Scand 2010; 122: 481–7.
73.Hajek, T, Kopecek, M, Hoschl, C, Alda, M. Smaller hippocampal volumes in patients with bipolar disorder are masked by exposure to lithium: a meta-analysis. J Psychiatry Neurosci 2012; 37: 333–43.
74.O'Connor, MK, Knapp, R, Husain, M, Rummans, T, Petrides, G, Smith, G, et al. The influence of age on the response of major depression to electroconvulsive therapy: a C.O.R.E. Report. Am J Geriatr Psychiatry 2001; 9: 382–90.
75.Nordenskjold, A, von Knorring, L, Engstrom, I. Predictors of the short-term responder rate of electroconvulsive therapy in depressive disorders – a population based study. BMC Psychiatry 2012; 12: 115.
76.Rhebergen, D, Huisman, A, Bouckaert, F, Kho, K, Kok, R, Sienaert, P, et al. Older age is associated with rapid remission of depression after electroconvulsive therapy: a latent class growth analysis. Am J Geriatr Psychiatry 2015; 23: 274–82.
77.Kellner, CH, Husain, MM, Knapp, RG, McCall, WV, Petrides, G, Rudorfer, MV, et al. Right unilateral ultrabrief pulse ECT in geriatric depression: Phase 1 of the PRIDE study. Am J Psychiatry 2016; 173: 1101–9.
78.Phillips, JL, Batten, LA, Tremblay, P, Aldosary, F, Blier, P. A prospective, longitudinal study of the effect of remission on cortical thickness and hippocampal volume in patients with treatment-resistant depression. Int J Neuropsychopharmacol 2015; 18: 19.
79.Colle, R, Cury, C, Chupin, M, Deflesselle, E, Hardy, P, Nasser, G, et al. Hippocampal volume predicts antidepressant efficacy in depressed patients without incomplete hippocampal inversion. Neuroimage Clin 2016; 12: 949–55.
80.Oltedal, L, Bartsch, H, Sorhaug, OJE, Kessler, U, Abbott, C, Dols, A, et al. The Global ECT-MRI Research Collaboration (GEMRIC): establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy. Neuroimage Clin 2017; 14: 422–32.
Type Description Title
Supplementary materials

Takamiya et al supplementary material
Takamiya et al supplementary material 1

 Unknown (23 KB)
23 KB


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed

Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis

  • Akihiro Takamiya (a1), Jun Ku Chung (a2), Kuo-ching Liang (a3), Ariel Graff-Guerrero (a4), Masaru Mimura (a3) and Taishiro Kishimoto (a5)...
Submit a response


No eLetters have been published for this article.


Reply to: Submit a response

Your details

Conflicting interests

Do you have any conflicting interests? *