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What causes the hippocampal volume decrease in depression? Are neurogenesis, glial changes and apoptosis implicated?

Boldizsár Czéh1, Paul J Lucassen

  • 1Clinical Neurobiology Laboratory, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany. bczeh@cnl-dpz.de

European Archives of Psychiatry and Clinical Neuroscience
|April 3, 2007
PubMed
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Depression is linked to hippocampal shrinkage, but cellular causes remain unclear. Research suggests changes in neuronal components and glial cells, not just cell death, may explain this volume reduction.

Area of Science:

  • Neuroscience
  • Cellular Biology
  • Psychiatry

Background:

  • In vivo imaging shows reduced hippocampal volume in depression.
  • Chronic stress models suggest glucocorticoid-induced neuronal death and suppressed neurogenesis cause shrinkage.
  • Existing human histopathology studies do not fully support massive neuronal loss or neurogenesis suppression.

Purpose of the Study:

  • To clarify the cellular mechanisms underlying hippocampal volume reduction in depression.
  • To evaluate the validity of proposed causes like neuronal death and suppressed neurogenesis in human depression.
  • To identify alternative cellular factors contributing to hippocampal shrinkage.

Main Methods:

  • Review of existing morphometrical and histopathological studies.

Related Experiment Videos

  • Critique of animal models of chronic stress and their relevance to human depression.
  • Emphasis on the need for stereological quantification in human hippocampal studies.

    • Main Results:

    • Histopathological studies in depressed individuals have not confirmed massive neuronal loss or suppressed dentate neurogenesis.
    • Observed structural changes and volume reduction in the hippocampus appear reversible.
    • Glucocorticoid effects in animal models may not directly translate to human depression's cellular mechanisms.

    Conclusions:

    • Hippocampal shrinkage in depression is likely due to alterations in somatodendritic, axonal, and synaptic components.
    • Putative glial changes may also contribute to reduced hippocampal volume.
    • Shifts in fluid balance or extracellular space changes cannot be ruled out as contributing factors.