title: Structural Plasticity of the Hippocampus and Amygdala Induced by Electroconvulsive Therapy in Major Depression.
abstract: BACKGROUND
  Electroconvulsive therapy (ECT) elicits a rapid and robust clinical response in patients with refractory depression. Neuroimaging measurements of structural plasticity relating to and predictive of ECT response may point to the mechanisms underlying rapid antidepressant effects and establish biomarkers to inform other treatments. Here, we determine the effects of diagnosis and of ECT on global and local variations of hippocampal and amygdala structures in major depression and predictors of ECT-related clinical response.
  
  
  METHODS
  Longitudinal changes in hippocampal and amygdala structures were examined in patients with major depression (N = 43, scanned three times: prior to ECT, after the second ECT session, and within 1 week of completing the ECT treatment series), referred for ECT as part of their standard clinical care. Cross-sectional comparisons with demographically similar controls (N = 32, scanned twice) established effects of diagnosis.
  
  
  RESULTS
  Patients showed smaller hippocampal volumes than controls at baseline (p < .04). Both the hippocampal and the amygdala volumes increased with ECT (p < .001) and in relation to symptom improvement (p < .01). Hippocampal volume at baseline predicted subsequent clinical response (p < .05). Shape analysis revealed pronounced morphometric changes in the anterior hippocampus and basolateral and centromedial amygdala. All structural measurements remained stable across time in controls.
  
  
  CONCLUSIONS
  ECT-induced neuroplasticity in the hippocampus and amygdala relates to improved clinical response and is pronounced in regions with prominent connections to ventromedial prefrontal cortex and other limbic structures. Smaller hippocampal volumes at baseline predict a more robust clinical response. Neurotrophic processes including neurogenesis shown in preclinical studies may underlie these structural changes.
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, Los Angeles, California.
authors.forename: Shantanu H
authors.initials: SH
authors.lastname: Joshi
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, California.
authors.forename: Randall T
authors.initials: RT
authors.lastname: Espinoza
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, Los Angeles, California.
authors.forename: Tara
authors.initials: T
authors.lastname: Pirnia
authors.affiliation: School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, AZ.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: School of Computing, Informatics, and Decision Systems Engineering, Arizona State University, AZ.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, Los Angeles, California.
authors.forename: Brandon
authors.initials: B
authors.lastname: Ayers
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, Los Angeles, California.
authors.forename: Amber
authors.initials: A
authors.lastname: Leaver
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, Los Angeles, California; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, California.
authors.forename: Roger P
authors.initials: RP
authors.lastname: Woods
authors.affiliation: Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California at Los Angeles, Los Angeles, California; Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, California. Electronic address: narr@ucla.edu.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Narr
mesh_terms: D000328:Adult; D000679:Amygdala / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000628:therapy*; D061218:Depressive Disorder, Treatment-Resistant / Q000628:therapy; D004565:Electroconvulsive Therapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009473:Neuronal Plasticity; D011569:Psychiatric Status Rating Scales; D016896:Treatment Outcome
keywords: Antidepressant; Brain stimulation; ECT; Limbic; Neuroimaging; Neuroplasticity
references.citation: Am J Psychiatry. 2006 Jan;163(1):28-40
references.pmid: 16390886
references.citation: Mol Psychiatry. 2008 Nov;13(11):993-1000
references.pmid: 18504424
references.citation: Neuroimage. 2002 Oct;17(2):825-41
references.pmid: 12377157
references.citation: Neuron. 2010 Jan 14;65(1):7-19
references.pmid: 20152109
references.citation: Convuls Ther. 1993;9(4):262-273
references.pmid: 11941222
references.citation: Neurosci Biobehav Rev. 2013 Feb;37(2):152-63
references.pmid: 23206667
references.citation: Brain Res. 2008 Feb 27;1196:41-52
references.pmid: 18234161
references.citation: Magn Reson Med. 2012 Aug;68(2):389-99
references.pmid: 22213578
references.citation: Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):3908-13
references.pmid: 8632988
references.citation: Exp Neurol. 1999 Apr;156(2):333-44
references.pmid: 10328940
references.citation: Neuron. 2002 Jan 31;33(3):341-55
references.pmid: 11832223
references.citation: J Comp Neurol. 1965 Jun;124(3):319-35
references.pmid: 5861717
references.citation: Neuroimage. 2013 Sep;78:111-34
references.pmid: 23587689
references.citation: Nature. 2011 Aug 25;476(7361):458-61
references.pmid: 21814201
references.citation: Am J Geriatr Psychiatry. 2013 May;21(5):493-6
references.pmid: 23570892
references.citation: IEEE Trans Med Imaging. 1998 Feb;17(1):87-97
references.pmid: 9617910
references.citation: Biol Psychiatry. 2006 Jun 15;59(12):1151-9
references.pmid: 16566899
references.citation: Biol Psychiatry. 2000 Jun 15;47(12):1043-9
references.pmid: 10862803
references.citation: Am J Psychiatry. 2014 Apr;171(4):395-7
references.pmid: 24687194
references.citation: World Psychiatry. 2014 Feb;13(1):44-6
references.pmid: 24497246
references.citation: Eur J Neurosci. 2005 Mar;21(5):1304-14
references.pmid: 15813940
references.citation: J ECT. 2003 Sep;19(3):139-47
references.pmid: 12972983
references.citation: J Neurosci. 1999 Jun 15;19(12):5034-43
references.pmid: 10366636
references.citation: Neuroimage. 2004 Jul;22(3):1060-75
references.pmid: 15219578
references.citation: Am J Psychiatry. 2006 Sep;163(9):1531-41; quiz 1666
references.pmid: 16946177
references.citation: Eur Neuropsychopharmacol. 2009 May;19(5):329-38
references.pmid: 19176277
references.citation: Neuroimage. 2004;23 Suppl 1:S69-84
references.pmid: 15501102
references.citation: Biol Psychiatry. 2010 Jan 15;67(2):125-32
references.pmid: 19880094
references.citation: J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
references.pmid: 9881538
references.citation: Neuroscience. 2002;114(2):411-6
references.pmid: 12204210
references.citation: Arch Gen Psychiatry. 2011 Jul;68(7):675-90
references.pmid: 21727252
references.citation: Am J Geriatr Psychiatry. 2007 Oct;15(10):899-905
references.pmid: 17911366
references.citation: Neuroimage. 2008 Apr 1;40(2):559-69
references.pmid: 18242102
references.citation: Mol Psychiatry. 2006 Jan;11(1):11-7
references.pmid: 16355250
references.citation: Mol Psychiatry. 2011 Feb;16(2):171-83
references.pmid: 20010892
references.citation: Neuropsychologia. 1971 Mar;9(1):97-113
references.pmid: 5146491
references.citation: J Psychiatry Neurosci. 2009 Sep;34(5):343-9
references.pmid: 19721844
references.citation: J Affect Disord. 2009 Sep;117(1-2):1-17
references.pmid: 19237202
references.citation: Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1387-92
references.pmid: 12552118
references.citation: Am J Psychiatry. 2012 Jul;169(7):693-703
references.pmid: 22535198
references.citation: Am J Psychiatry. 2004 Nov;161(11):1957-66
references.pmid: 15514393
references.citation: J ECT. 2010 Mar;26(1):62-7
references.pmid: 20190603
references.citation: J Clin Psychiatry. 2004 Apr;65(4):485-91
references.pmid: 15119910
references.citation: Br J Psychiatry. 1979 Apr;134:382-9
references.pmid: 444788
references.citation: Biol Psychiatry. 2010 Mar 1;67(5):446-57
references.pmid: 20015486
references.citation: Int J Dev Neurosci. 2010 May;28(3):227-32
references.pmid: 20170723
references.citation: J ECT. 2014 Jun;30(2):143-51
references.pmid: 24810772
references.citation: Int J Neuropsychopharmacol. 2013 Mar;16(2):339-50
references.pmid: 22310305
references.citation: J Psychiatry Neurosci. 2009 Jan;34(1):41-54
references.pmid: 19125212
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11352-7
references.pmid: 18682560
references.citation: Neuropsychopharmacology. 2010 Jan;35(1):192-216
references.pmid: 19693001
references.citation: Nat Rev Neurosci. 2013 Sep;14(9):609-25
references.pmid: 23942470
references.citation: J Neurosci. 2000 Dec 15;20(24):9104-10
references.pmid: 11124987
references.citation: Curr Opin Pharmacol. 2007 Feb;7(1):18-21
references.pmid: 17049922
references.citation: Psychiatry Investig. 2010 Dec;7(4):231-5
references.pmid: 21253405
references.citation: Arch Gen Psychiatry. 2008 Oct;65(10):1156-65
references.pmid: 18838632
references.citation: Psychol Med. 2004 Jan;34(1):73-82
references.pmid: 14971628
references.citation: Mol Psychiatry. 2011 Mar;16(3):252-64
references.pmid: 20661246
references.citation: IEEE Trans Med Imaging. 2007 Jun;26(6):853-65
references.pmid: 17679336
references.citation: Am J Psychiatry. 2008 Feb;165(2):229-37
references.pmid: 17986679
references.citation: Nat Rev Neurosci. 2011 Oct;12(10):585-601
references.pmid: 21897434
references.citation: Psychiatry Res. 2013 Dec 30;214(3):197-203
references.pmid: 24090511
references.citation: Am J Psychiatry. 2003 Feb;160(2):237
references.pmid: 12562566
references.citation: J Neurosci. 1995 Nov;15(11):7539-47
references.pmid: 7472505
references.citation: Science. 2012 Oct 5;338(6103):72-5
references.pmid: 23042885
references.citation: Behav Pharmacol. 2007 Sep;18(5-6):391-418
references.pmid: 17762509
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1156-61
references.pmid: 24379394
references.citation: Am J Psychiatry. 2006 Sep;163(9):1519-30; quiz 1665
references.pmid: 16946176
references.citation: Am J Psychiatry. 2003 Aug;160(8):1516-8
references.pmid: 12900317
references.citation: J Neurol Neurosurg Psychiatry. 1960 Feb;23:56-62
references.pmid: 14399272
references.citation: Biol Psychiatry. 2008 Jun 15;63(12):1155-62
references.pmid: 18281017
references.citation: Neuroreport. 1998 Jun 22;9(9):2023-8
references.pmid: 9674587
references.citation: Am J Psychiatry. 1990 Aug;147(8):1029-35
references.pmid: 2375437