Elsevier

Biological Psychiatry

Volume 56, Issue 9, 1 November 2004, Pages 640-650
Biological Psychiatry

Original articles
Cellular changes in the postmortem hippocampus in major depression

https://doi.org/10.1016/j.biopsych.2004.08.022Get rights and content

Background

Imaging studies report that hippocampal volume is decreased in major depressive disorder (MDD). A cellular basis for reduced hippocampal volume in MDD has not been identified.

Methods

Sections of right hippocampus were collected in 19 subjects with MDD and 21 normal control subjects. The density of pyramidal neurons, dentate granule cell neurons, glia, and the size of the neuronal somal area were measured in systematic, randomly placed three-dimensional optical disector counting boxes.

Results

In MDD, cryostat-cut hippocampal sections shrink in depth a significant 18% greater amount than in control subjects. The density of granule cells and glia in the dentate gyrus and pyramidal neurons and glia in all cornv ammonis (CA)/hippocampal subfields is significantly increased by 30% –35% in MDD. The average soma size of pyramidal neurons is significantly decreased in MDD.

Conclusion

In MDD, the packing density of glia, pyramidal neurons, and granule cell neurons is significantly increased in all hippocampal subfields and the dentate gyrus, and pyramidal neuron soma size is significantly decreased as well. It is suggested that a significant reduction in neuropil in MDD may account for decreased hippocampal volume detected by neuroimaging. In addition, differential shrinkage of frozen sections of the hippocampus suggests differential water content in hippocampus in MDD.

Section snippets

Methods and materials

Tissues from 19 depressed subjects and 21 age-matched psychiatrically healthy control subjects were obtained at autopsy from the Coroner’s Office of Cuyahoga County, Cleveland, Ohio, USA. An ethical protocol approved by the Institutional Review Board of the University Hospitals of Cleveland was used, and informed written consent was obtained from the next-of-kin for all subjects. Blood and urine samples from all subjects were examined by the coroner’s office for psychotropic medications and

Age, postmortem interval, and tissue pH

There was no significant difference between subject groups in age, postmortem interval (time between death and freezing tissue), or tissue pH. The average age (years, mean ± SE) of the two groups was 57.9 ± 3.6 (range 26–84) for control and 57.4 ± 3.9 (range: 30–87) for depressive subjects. The average postmortem interval (hours) of the two groups was 20.5 ± 1.1 for control and 19.3 ± 1.2 for depressive subjects. The average pH of cerebellar tissue was 6.5 ± .1 for control and 6.6 ± .1 for

Discussion

Several imaging studies report that hippocampal volume is decreased in MDD, yet no cellular basis for a reduction in hippocampal volume has been identified. To the authors’ knowledge, this is the first study to evaluate neuronal and glial density and soma and glial nucleus size in postmortem hippocampus in a large cohort of subjects with MDD and age-matched psychiatrically normal control subjects. Three-dimensional cell counting methods were applied to the evaluation of neurons and glia in the

References (52)

  • B.D. Rusch et al.

    Hippocampal morphometry in depressed patients and control subjectsrelations to anxiety symptoms

    Biol Psychiatry

    (2001)
  • D.C. Steffens et al.

    Hippocampal volume in geriatric depression

    Biol Psychiatry

    (2000)
  • H.B. Uylings et al.

    Morphometry of size/volume variables and comparison of their bivariate relations in the nervous system under different conditions

    J Neurosci Methods

    (1986)
  • K. Vakili et al.

    Hippocampal volume in primary unipolar major depressionA magnetic resonance imaging study

    Biol Psychiatry

    (2000)
  • B.B. Andersen et al.

    Pronounced loss of cell nuclei and anisotropic deformation of thick sections

    J Microsc

    (1999)
  • S.E. Arnold et al.

    Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions

    Am J Psychiatry

    (1995)
  • J.D. Bremner et al.

    Hippocampal volume reduction in major depression

    Am J Psychiatry

    (2000)
  • S. Campbell et al.

    Lower hippocampal volume in patients suffering from depressionA meta-analysis

    Am J Psychiatry

    (2004)
  • D. Cotter et al.

    Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder

    Cereb Cortex

    (2002)
  • D. Cotter et al.

    Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder

    Arch Gen Psychiatry

    (2001)
  • G. Danscher

    Histochemical demonstration of heavy metals. A revised version of the sulphide silver method suitable for both light and electronmicroscopy

    Histochemistry

    (1981)
  • K.A. Dorph-Petersen et al.

    Tissue shrinkage and unbiased stereological estimation of particle number and size

    J Microsc

    (2001)
  • D. Dowlatshahi et al.

    Increased hippocampal supragranular Timm staining in subjects with bipolar disorder

    Neuroreport

    (2000)
  • Y. Dwivedi et al.

    Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects

    Arch Gen Psychiatry

    (2003)
  • S.H. Fatemi et al.

    Reduction in Reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression

    Mol Psychiatry

    (2000)
  • M.B. First et al.

    Structured Clinical Interview for DSM-IV Axis I Disorders—Patient Edition (SCID-I/P, Version 2.0).

    (1996)

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