Lower hippocampal volume in patients suffering from depression: a meta-analysis.

OBJECTIVE A number of studies have used magnetic resonance imaging to examine volumetric differences in temporal structures in subjects suffering from major depressive disorder. Studies have reported lower hippocampal and amygdala volume, but results have been inconsistent. The authors were interested, therefore, in examining these studies in the aggregate in order to determine whether hippocampal volume is lower in major depressive disorder. They also examined factors that may contribute to the disparate results in the literature. METHOD A meta-analysis was conducted of studies that used magnetic resonance imaging to assess the volume of the hippocampus and related structures in patients with major depressive disorder. RESULTS Patients were seen to have lower hippocampal volume relative to comparison subjects, detectable if the hippocampus was measured as a discrete structure. CONCLUSIONS Although the effect of major depressive disorder on amygdala volume remains to be conclusively established, inclusion of the amygdala with the hippocampus appears to have decreased the likelihood of detecting volumetric differences in either structure. Slice thickness or other scan parameters did not account for a substantive amount of the variance in results, whereas clinical variables of the populations studied, such as duration of illness or presence of abuse, may account for much of the discrepancy between findings.

[1]  Y. Sheline 3D MRI studies of neuroanatomic changes in unipolar major depression: the role of stress and medical comorbidity , 2000, Biological Psychiatry.

[2]  Louis Lemieux,et al.  Amygdala enlargement in dysthymia—a volumetric study of patients with temporal lobe epilepsy , 1999, Biological Psychiatry.

[3]  H. Duvernoy,et al.  The Human Hippocampus: Functional Anatomy, Vascularization and Serial Sections with MRI , 1997 .

[4]  W. Drevets Neuroimaging studies of mood disorders , 2000, Biological Psychiatry.

[5]  L. Radloff The CES-D Scale , 1977 .

[6]  J. Soares,et al.  The anatomy of mood disorders—review of structural neuroimaging studies , 1997, Biological Psychiatry.

[7]  C. Nemeroff,et al.  Hypercortisolemia and hippocampal changes in depression , 1993, Psychiatry Research.

[8]  R. Sapolsky,et al.  Hippocampal damage associated with prolonged glucocorticoid exposure in primates , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[9]  L R Schad,et al.  Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia. , 1997, Journal of affective disorders.

[10]  J. Mendels,et al.  Urinary free Cortisol excretion in depression , 1976, Psychological Medicine.

[11]  Bruce S. McEwen,et al.  Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons , 1992, Brain Research.

[12]  E. Olsson,et al.  Impaired neuropsychological performance in euthymic patients with recurring mood disorders. , 1997, The Journal of clinical psychiatry.

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

[14]  Eva Meisenzahl,et al.  Enlargement of the amygdala in patients with a first episode of major depression , 2002, Biological Psychiatry.

[15]  Eric Vermetten,et al.  Childhood trauma associated with smaller hippocampal volume in women with major depression. , 2002, The American journal of psychiatry.

[16]  Klaus P. Ebmeier,et al.  Cortical grey matter reductions associated with treatment-resistant chronic unipolar depression , 1998, British Journal of Psychiatry.

[17]  G Buzsáki,et al.  The hippocampo-neocortical dialogue. , 1996, Cerebral cortex.

[18]  M Ashtari,et al.  Hippocampal/amygdala volumes in geriatric depression , 1999, Psychological Medicine.

[19]  U. Grenander,et al.  Hippocampal morphometry in schizophrenia by high dimensional brain mapping. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[20]  Deborah A Yurgelun-Todd,et al.  Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study , 2000, Biological Psychiatry.

[21]  B. Carroll The Dexamethasone Suppression Test for Melancholia , 1982, British Journal of Psychiatry.

[22]  B. McEwen Stress and hippocampal plasticity. , 1999, Annual review of neuroscience.

[23]  B. Roth,et al.  Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression∗ ∗ See accompanying Editorial, in this issue. , 1999, Biological Psychiatry.

[24]  M. Miller,et al.  High-dimensional mapping of the hippocampus in depression. , 2003, The American journal of psychiatry.

[25]  L R Schad,et al.  [Volumetric brain findings in late depression. A study with quantified magnetic resonance tomography]. , 1998, Der Nervenarzt.

[26]  R. Sapolsky A mechanism for glucocorticoid toxicity in the hippocampus: increased neuronal vulnerability to metabolic insults , 1985, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

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

[29]  J. Csernansky,et al.  Hippocampal atrophy in recurrent major depression. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  R. Kerwin,et al.  Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. , 2001, Archives of general psychiatry.

[31]  G. Rajkowska,et al.  Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells , 2000, Biological Psychiatry.

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

[33]  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.

[34]  H. Cameron,et al.  Phenytoin prevents stress‐ and corticosterone‐induced atrophy of CA3 pyramidal neurons , 1992, Hippocampus.

[35]  James R MacFall,et al.  Hippocampal volume in geriatric depression , 2000, Biological Psychiatry.

[36]  H. Möller,et al.  Hippocampal changes in patients with a first episode of major depression. , 2002, The American journal of psychiatry.

[37]  G. Bartzokis,et al.  Reliability of in vivo volume measures of hippocampus and other brain structures using MRI. , 1993, Magnetic resonance imaging.

[38]  Bruno Giordani,et al.  Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s disease , 1999, Biological Psychiatry.

[39]  D. Guidolin,et al.  Glucocorticoids depress activity-dependent expression of BDNF mRNA in hippocampal neurones. , 1993, Neuroreport.

[40]  Oliver T Wolf,et al.  MRI volume of the amygdala: a reliable method allowing separation from the hippocampal formation , 1999, Psychiatry Research: Neuroimaging.

[41]  A. Moffoot,et al.  An analysis of memory dysfunction in major depression. , 1995, Journal of affective disorders.

[42]  M. Garabedian,et al.  Glucocorticoid receptor-mediated cell cycle arrest is achieved through distinct cell-specific transcriptional regulatory mechanisms , 1997, Molecular and cellular biology.

[43]  Alexander Hammers,et al.  Evidence of a smaller left hippocampus and left temporal horn in both patients with first episode schizophrenia and normal control subjects , 2000, Psychiatry Research: Neuroimaging.

[44]  P. Perruchet,et al.  The dissociation of explicit and implicit memory in depressed patients , 1994, Psychological Medicine.

[45]  Eric Vermetten,et al.  Reduced volume of orbitofrontal cortex in major depression , 2002, Biological Psychiatry.

[46]  A. Dimascio,et al.  Cognitive and performance deficits in depression. , 1982, Psychopharmacology bulletin.

[47]  J. Douglas Bremner,et al.  Does stress damage the brain? , 1999, Biological Psychiatry.

[48]  Marcus E Raichle,et al.  Volumetric reduction in left subgenual prefrontal cortex in early onset depression , 2002, Biological Psychiatry.

[49]  C. Coffey,et al.  Quantitative cerebral anatomy in depression. A controlled magnetic resonance imaging study. , 1993, Archives of general psychiatry.

[50]  Glenda M MacQueen,et al.  Course of illness, hippocampal function, and hippocampal volume in major depression , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[51]  J. Price,et al.  Low glial numbers in the amygdala in major depressive disorder , 2002, Biological Psychiatry.

[52]  G. MacQueen,et al.  Recollection memory deficits in patients with major depressive disorder predicted by past depressions but not current mood state or treatment status , 2002, Psychological Medicine.

[53]  G. Bartzokis,et al.  An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia , 2000, Biological Psychiatry.

[54]  R. McKay,et al.  Restoring production of hippocampal neurons in old age , 1999, Nature Neuroscience.

[55]  B. McEwen,et al.  Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. , 1999, European journal of pharmacology.

[56]  F Andermann,et al.  Anatomic basis of amygdaloid and hippocampal volume measurement by magnetic resonance imaging , 1992, Neurology.

[57]  M. Miller,et al.  Hippocampal deformities in schizophrenia characterized by high dimensional brain mapping. , 2002, The American journal of psychiatry.

[58]  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.

[59]  E Mervaala,et al.  Quantitative MRI of the hippocampus and amygdala in severe depression , 2000, Psychological Medicine.

[60]  R. Sapolsky,et al.  The possibility of neurotoxicity in the hippocampus in major depression: a primer on neuron death , 2000, Biological Psychiatry.

[61]  Richard J Davidson,et al.  Hippocampal morphometry in depressed patients and control subjects: relations to anxiety symptoms , 2001, Biological Psychiatry.