Grey matter volume increase following electroconvulsive therapy in patients with late life depression: a longitudinal MRI study.

BACKGROUND The evidence on the mechanisms of action of electroconvulsive therapy (ECT) has grown over the past decades. Recent studies show an ECT-related increase in hippocampal, amygdala and subgenual cortex volume. We examined grey matter volume changes following ECT using voxel-based morphometry (VBM) whole brain analysis in patients with severe late life depression (LLD). METHODS Elderly patients with unipolar depression were treated twice weekly with right unilateral ECT until remission on the Montgomery-Åsberg Depression Rating Scale (MADRS) was achieved. Cognition (Mini Mental State Examination) and psychomotor changes (CORE Assessment) were monitored at baseline and 1 week after the last session of ECT. We performed 3 T structural MRI at both time points. We used the VBM8 toolbox in SPM8 to study grey matter volume changes. Paired t tests were used to compare pre- and post-ECT grey matter volume (voxel-level family-wise error threshold p < 0.05) and to assess clinical response. RESULTS Twenty-eight patients (mean age 71.9 ± 7.8 yr, 8 men) participated in our study. Patients received a mean of 11.2 ± 4 sessions of ECT. The remission rate was 78.6%. Cognition, psychomotor agitation and psychomotor retardation improved significantly (p < 0.001). Right-hemispheric grey matter volume was increased in the caudate nucleus, medial temporal lobe (including hippocampus and amygdala), insula and posterior superior temporal regions but did not correlate with MADRS score. Grey matter volume increase in the caudate nucleus region correlated significantly with total CORE Assessment score (r = 0.63; p < 0.001). LIMITATIONS Not all participants were medication-free. CONCLUSION Electroconvulsive therapy in patients with LLD is associated with significant grey matter volume increase, which is most pronounced ipsilateral to the stimulation side.

[1]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[2]  Christos Davatzikos,et al.  Depressive symptoms and brain volumes in older adults: a longitudinal magnetic resonance imaging study. , 2009, Journal of psychiatry & neuroscience : JPN.

[3]  Anil Gholkar,et al.  A longitudinal study of hippocampal volume, cortisol levels, and cognition in older depressed subjects. , 2004, The American journal of psychiatry.

[4]  Hans-Jürgen Möller,et al.  Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study. , 2008, Journal of psychiatry & neuroscience : JPN.

[5]  R. Kendell,et al.  Cerebral and Brain Stem Changes After ECT Revealed by Nuclear Magnetic Resonance Imaging , 1987, British Journal of Psychiatry.

[6]  Allison C. Nugent,et al.  Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder , 2011, NeuroImage.

[7]  M. Åsberg,et al.  A New Depression Scale Designed to be Sensitive to Change , 1979, British Journal of Psychiatry.

[8]  Ferath Kherif,et al.  Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders , 2013, Proceedings of the National Academy of Sciences.

[9]  O. Abe,et al.  Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra provides reduced effect of scanner for cortex volumetry with atlas-based method in healthy subjects , 2013, Neuroradiology.

[10]  Ian H. Gotlib,et al.  Reduced caudate gray matter volume in women with major depressive disorder , 2008, Psychiatry Research: Neuroimaging.

[11]  I. Hickie,et al.  Prediction of ECT Response: Validation of a Refined Sign-Based (CORE) System for Defining Melancholia , 1996, British Journal of Psychiatry.

[12]  T. Bolwig,et al.  Electroconvulsive therapy, hypertensive surge, blood-brain barrier breach, and amnesia: exploring the evidence for a connection. , 2014, The journal of ECT.

[13]  S. Couillard-Després,et al.  Hippocampal Neurogenesis and Antidepressive Therapy: Shocking Relations , 2014, Neural plasticity.

[14]  M. Thase,et al.  Acute efficacy of ECT in the treatment of major depression in the old-old. , 1999, The American journal of psychiatry.

[15]  Modelling late‐life depression , 2003, International journal of geriatric psychiatry.

[16]  K. Krishnan,et al.  Magnetic resonance imaging of the caudate nuclei in depression. Preliminary observations. , 1992, Archives of general psychiatry.

[17]  D. McLoughlin,et al.  Objective Cognitive Performance Associated with Electroconvulsive Therapy for Depression: A Systematic Review and Meta-Analysis , 2010, Biological Psychiatry.

[18]  M. Yücel,et al.  An MRI study of the superior temporal subregions in patients with current and past major depression , 2010, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[19]  Nikolaus Weiskopf,et al.  A comparison between voxel-based cortical thickness and voxel-based morphometry in normal aging , 2009, NeuroImage.

[20]  Won Hee Lee,et al.  Regional electric field induced by electroconvulsive therapy in a realistic finite element head model: Influence of white matter anisotropic conductivity , 2012, NeuroImage.

[21]  D. Steffens,et al.  Structural neuroimaging of geriatric depression. , 2011, The Psychiatric clinics of North America.

[22]  Feng Li,et al.  Voxel-based morphometry study of the insular cortex in female patients with current and remitted depression , 2014, Neuroscience.

[23]  Alan J. Thomas,et al.  Morphometric analysis of neuronal and glial cell pathology in the caudate nucleus in late-life depression. , 2011, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[24]  M. Furey,et al.  Brain structural and functional abnormalities in mood disorders: implications for neurocircuitry models of depression , 2008, Brain Structure and Function.

[25]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[26]  I. Hickie,et al.  The neurobiology of depression in later-life: Clinical, neuropsychological, neuroimaging and pathophysiological features , 2012, Progress in Neurobiology.

[27]  Klaus P. Ebmeier,et al.  A systematic review and meta-analysis of magnetic resonance imaging studies in late-life depression. , 2012, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[28]  Thomas E. Nichols,et al.  Post-ECT increases in MRI regional T2 relaxation times and their relationship to cognitive side effects: A pilot study , 1994, Psychiatry Research.

[29]  P. Scheltens,et al.  The structure of the geriatric depressed brain and response to electroconvulsive therapy , 2014, Psychiatry Research: Neuroimaging.

[30]  Steven C. R. Williams,et al.  A comprehensive testing protocol for MRI neuroanatomical segmentation techniques: Evaluation of a novel lateral ventricle segmentation method , 2011, NeuroImage.

[31]  A. Rush,et al.  The influence of age on the response of major depression to electroconvulsive therapy: a C.O.R.E. Report. , 2001, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[32]  Michael I. Miller,et al.  APOE related hippocampal shape alteration in geriatric depression , 2009, NeuroImage.

[33]  Liberty S. Hamilton,et al.  Hippocampal morphology and distinguishing late-onset from early-onset elderly depression. , 2008, The American journal of psychiatry.

[34]  Andreas Meyer-Lindenberg,et al.  Electroconvulsive Therapy Induces Neurogenesis in Frontal Rat Brain Areas , 2013, PloS one.

[35]  A. Zwinderman,et al.  A Meta-Analysis of Electroconvulsive Therapy Efficacy in Depression , 2003, The journal of ECT.

[36]  Nick C Fox,et al.  Pitfalls in the Use of Voxel-Based Morphometry as a Biomarker: Examples from Huntington Disease , 2010, American Journal of Neuroradiology.

[37]  Robert Barber,et al.  Hippocampal volume change in depression: Late- and early-onset illness compared , 2004, British Journal of Psychiatry.

[38]  Peter R Schofield,et al.  Serotonin transporter gene status predicts caudate nucleus but not amygdala or hippocampal volumes in older persons with major depression. , 2007, Journal of affective disorders.

[39]  Indira Tendolkar,et al.  Electroconvulsive therapy increases hippocampal and amygdala volume in therapy refractory depression: A longitudinal pilot study , 2013, Psychiatry Research: Neuroimaging.

[40]  John Ashburner,et al.  A fast diffeomorphic image registration algorithm , 2007, NeuroImage.

[41]  P. Sienaert,et al.  Efficacy and cognitive side effects after brief pulse and ultrabrief pulse right unilateral electroconvulsive therapy for major depression: a randomized, double-blind, controlled study. , 2013, The Journal of clinical psychiatry.

[42]  S. Resnick,et al.  Longitudinal Magnetic Resonance Imaging Studies of Older Adults: A Shrinking Brain , 2003, The Journal of Neuroscience.

[43]  M. Stek,et al.  The efficacy and safety of ECT in depressed older adults: a literature review , 2003, International journal of geriatric psychiatry.

[44]  Elna-Marie Larsson,et al.  Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression: A Volumetric Magnetic Resonance Imaging Study , 2010, The journal of ECT.

[45]  A. Beekman,et al.  White matter hyperintensities, medial temporal lobe atrophy, cortical atrophy, and response to electroconvulsive therapy in severely depressed elderly patients. , 2011, The Journal of clinical psychiatry.

[46]  D. Yurgelun-Todd,et al.  Striatal structure and function in mood disorders: a comprehensive review. , 2010, Bipolar disorders.

[47]  Hannie C. Comijs,et al.  Depression, Hypothalamic Pituitary Adrenal Axis, and Hippocampal and Entorhinal Cortex Volumes—The SMART Medea Study , 2011, Biological Psychiatry.

[48]  John R. Geddes,et al.  Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis , 2003, The Lancet.

[49]  Kay Wilhelm,et al.  Caudate nucleus volumes and genetic determinants of homocysteine metabolism in the prediction of psychomotor speed in older persons with depression. , 2002, The American journal of psychiatry.

[50]  B. Gangadhar,et al.  MRI T2 relaxometry of brain regions and cognitive dysfunction following electroconvulsive therapy , 2007, Indian journal of psychiatry.

[51]  Ellen Frank,et al.  Anatomical MRI study of hippocampus and amygdala in patients with current and remitted major depression , 2004, Psychiatry Research: Neuroimaging.

[52]  Anatol C. Kreitzer,et al.  Plasticity in gray and white: neuroimaging changes in brain structure during learning , 2012, Nature Neuroscience.

[53]  E. Larsson,et al.  Hippocampal volume in relation to clinical and cognitive outcome after electroconvulsive therapy in depression , 2013, Acta psychiatrica Scandinavica.

[54]  R. Tadayonnejad,et al.  Brain Network Dysfunction in Late-Life Depression , 2014, Journal of geriatric psychiatry and neurology.

[55]  P. Sienaert,et al.  ECT: Its Brain Enabling Effects A Review of Electroconvulsive Therapy–Induced Structural Brain Plasticity , 2014, The journal of ECT.

[56]  S. Patten,et al.  Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. IV. Neurostimulation therapies. , 2009, Journal of affective disorders.

[57]  Jiing-Feng Lirng,et al.  Cortical and Subcortical Abnormalities in Late-Onset Depression With History of Suicide Attempts Investigated With MRI and Voxel-Based Morphometry , 2010, Journal of geriatric psychiatry and neurology.

[58]  Elaine M. Dillingham,et al.  Effect of concomitant pharmacotherapy on electroconvulsive therapy outcomes: short-term efficacy and adverse effects. , 2009, Archives of general psychiatry.

[59]  Daniella J. Furman,et al.  Frontostriatal functional connectivity in major depressive disorder , 2011, Biology of Mood & Anxiety Disorders.

[60]  K. Krishnan,et al.  Magnetic-resonance morphometry in patients with major depression , 1998, Psychiatry Research: Neuroimaging.

[61]  A. Toga,et al.  Three-dimensional surface mapping of the caudate nucleus in late-life depression. , 2009, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.