Amygdala volume in major depressive disorder: a meta-analysis of magnetic resonance imaging studies

Major depressive disorder has been associated with volumetric abnormality in the amygdala. In this meta-analysis we examine results from magnetic resonance imaging volumetry studies of the amygdala in depression in order to assess both the nature of the relationship between depression and amygdala volume as well as the influence of extraexperimental factors that may account for significant variability in reported findings. We searched PubMed and ISI Web of Knowledge databases for articles published from 1985 to 2008 that used the wildcard terms ‘Depress*’ and ‘Amygdal*’ in the title, keywords or abstract. From the 13 studies that met inclusion criteria for our meta-analysis, we calculated aggregate effect size and heterogeneity estimates from amygdala volumetric data; we then used meta-regression to determine whether variability in specific extraexperimental factors accounted for variability in findings. The lack of a reliable difference in amygdala volume between depressed and never-depressed individuals was accounted for by a positive correlation between amygdala volume differences and the proportion of medicated depressed persons in study samples: whereas the aggregate effect size calculated from studies that included only medicated individuals indicated that amygdala volume was significantly increased in depressed relative to healthy persons, studies with only unmedicated depressed individuals showed a reliable decrease in amygdala volume in depression. These findings are consistent with a formulation in which an antidepressant-mediated increase in levels of brain-derived neurotrophic factor promotes neurogenesis and protects against glucocorticoid toxicity in the amygdala in medicated but not in unmedicated depression.

[1]  M. Raichle,et al.  A functional anatomical study of unipolar depression , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[2]  R. Adolphs,et al.  Impaired Judgments of Sadness But Not Happiness Following Bilateral Amygdala Damage , 2004, Journal of Cognitive Neuroscience.

[3]  Sarah H Lisanby,et al.  Antidepressant-Induced Neurogenesis in the Hippocampus of Adult Nonhuman Primates , 2007, The Journal of Neuroscience.

[4]  P. Lachenbruch.  Statistical Power Analysis for the Behavioral Sciences (2nd ed.) , 1989 .

[5]  L. Staib,et al.  Hippocampal volume reduction in major depression. , 2000, The American journal of psychiatry.

[6]  Yvette I. Sheline,et al.  Amygdala core nuclei volumes are decreased in recurrent major depression , 1998, Neuroreport.

[7]  G. MacQueen,et al.  Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication , 2001, Biological Psychiatry.

[8]  C. Woolley,et al.  Morphological sex differences and laterality in the prepubertal medial amygdala , 2007, The Journal of comparative neurology.

[9]  G. Marsicano,et al.  Involvement of brain‐derived neurotrophic factor in cannabinoid receptor‐dependent protection against excitotoxicity , 2004, The European journal of neuroscience.

[10]  L. Eng,et al.  Glutamine synthetase immunoreactivity is present in oligodendroglia of various regions of the central nervous system , 1990, Glia.

[11]  Stephen J. Sharp,et al.  Meta-analysis regression , 1998 .

[12]  A. Tingström,et al.  Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat amygdala , 2004, Biological Psychiatry.

[13]  Yvette I. Sheline,et al.  Depression Duration But Not Age Predicts Hippocampal Volume Loss in Medically Healthy Women with Recurrent Major Depression , 1999, The Journal of Neuroscience.

[14]  L. Lemieux,et al.  Increased amygdala volumes in female and depressed humans. A quantitative magnetic resonance imaging study , 2000, Neuroscience Letters.

[15]  M. Héry,et al.  Agomelatine, a New Antidepressant, Induces Regional Changes in Hippocampal Neurogenesis , 2006, Biological Psychiatry.

[16]  B. Ravnkilde,et al.  Hippocampal volume and depression: a meta-analysis of MRI studies. , 2004, The American journal of psychiatry.

[17]  D. Perrett,et al.  A differential neural response in the human amygdala to fearful and happy facial expressions , 1996, Nature.

[18]  M. Raichle,et al.  Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism , 2002, European Neuropsychopharmacology.

[19]  J P Hatch,et al.  Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder , 2007, Molecular Psychiatry.

[20]  Timothy J. Robinson,et al.  Multilevel Analysis: Techniques and Applications , 2002 .

[21]  R. Hen,et al.  Chronic Fluoxetine Stimulates Maturation and Synaptic Plasticity of Adult-Born Hippocampal Granule Cells , 2008, The Journal of Neuroscience.

[22]  J. P. Hamilton,et al.  Neural Substrates of Increased Memory Sensitivity for Negative Stimuli in Major Depression , 2008, Biological Psychiatry.

[23]  Xiao-Hua Zhou,et al.  Statistical Methods for Meta‐Analysis , 2008 .

[24]  Joseph E LeDoux,et al.  Localization of glucocorticoid receptors at postsynaptic membranes in the lateral amygdala , 2005, Neuroscience.

[25]  J. Price,et al.  Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes , 2004, Biological Psychiatry.

[26]  L Cipolotti,et al.  A volumetric study of hippocampus and amygdala in depressed patients with subjective memory problems. , 2000, The Journal of neuropsychiatry and clinical neurosciences.

[27]  P. Fox,et al.  Cingulate function in depression: a potential predictor of treatment response , 1997, Neuroreport.

[28]  A. Parent,et al.  Newly generated neurons in the amygdala and adjoining cortex of adult primates , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[29]  R. Duman,et al.  Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[30]  Michael Davis,et al.  Amygdala BDNF signaling is required for consolidation but not encoding of extinction , 2006, Nature Neuroscience.

[31]  Greg J Siegle,et al.  Relationships between Amygdala Volume and Activity during Emotional Information Processing Tasks in Depressed and Never‐Depressed Individuals , 2003, Annals of the New York Academy of Sciences.

[32]  James L. McGaugh,et al.  The amygdala and emotional memory , 1995, Nature.

[33]  Eric J. Nestler,et al.  Chronic Antidepressant Treatment Increases Neurogenesis in Adult Rat Hippocampus , 2000, The Journal of Neuroscience.

[34]  Hans-Jürgen Möller,et al.  Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects , 2003, Biological Psychiatry.

[35]  Michael Davis,et al.  Brain-Derived Neurotrophic Factor and Tyrosine Kinase Receptor B Involvement in Amygdala-Dependent Fear Conditioning , 2004, The Journal of Neuroscience.

[36]  R. Adolphs,et al.  Impaired declarative memory for emotional material following bilateral amygdala damage in humans. , 1997, Learning & memory.

[37]  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.

[38]  M. Yates.  Recurrent Major Depression , 1992 .

[39]  H. Kraemer,et al.  Untreated depression and hippocampal volume loss. , 2003, The American journal of psychiatry.

[40]  J. Häggblad,et al.  Platelet-Derived Growth Factor (PDGF-BB) and Brain-Derived Neurotrophic Factor (BDNF) induce striatal neurogenesis in adult rats with 6-hydroxydopamine lesions , 2005, Neuroscience.

[41]  Michael Marriott,et al.  Lower hippocampal volume in patients suffering from depression: a meta-analysis. , 2004, The American journal of psychiatry.

[42]  Hans-Jürgen Möller,et al.  Hippocampal and amygdala changes in patients with major depressive disorder and healthy controls during a 1-year follow-up. , 2004, The Journal of clinical psychiatry.

[43]  G. Weniger,et al.  Abnormal size of the amygdala predicts impaired emotional memory in major depressive disorder. , 2006, Journal of affective disorders.

[44]  R. Sapolsky,et al.  Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. , 2000, Archives of general psychiatry.

[45]  Jacob Cohen.  Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[46]  Ita G. G. Kreft,et al.  Multilevel Analysis Methods , 1994 .

[47]  R. Sapolsky.  Why Stress Is Bad for Your Brain , 1996, Science.

[48]  A. Tingström,et al.  Electroconvulsive seizures induce proliferation of NG2-expressing glial cells in adult rat hippocampus , 2003, Biological Psychiatry.

[49]  G. A. Marcoulides,et al.  Multilevel Analysis Techniques and Applications , 2002 .

[50]  C. Lange,et al.  Enlarged amygdala volume and reduced hippocampal volume in young women with major depression , 2004, Psychological Medicine.

[51]  Michael I. Miller,et al.  Amygdala Volume Analysis in Female Twins with Major Depression , 2007, Biological Psychiatry.

[52]  Yan Liu,et al.  The effects of social environment on adult neurogenesis in the female prairie vole. , 2002, Journal of neurobiology.

[53]  Angela L. Lee,et al.  Stress and depression: possible links to neuron death in the hippocampus. , 2002, Bipolar disorders.

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

[55]  W. R. Sharp,et al.  A Steering and Visualization Toolkit for Distributed Applications , 2006, PDPTA.

[56]  H. Scharfman,et al.  Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats , 2005, Experimental Neurology.

[57]  Victoria Arango,et al.  Volumetric Analysis of the Prefrontal Cortex, Amygdala, and Hippocampus in Major Depression , 2004, Neuropsychopharmacology.

[58]  E. Arenas,et al.  Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulate the phenotype and prevent degenerative changes in striatal projection neurons after excitotoxicity in vivo , 1999, Neuroscience.