Hippocampus and Depression


We used to believe that brain tissue couldn’t regenerate, couldn’t grow only prenatal and during early postnatal development. Since than neurogenesis or the process creation of new neurons (nerve cells) has been demonstrated in vitro and vivo experiments and animal research.
It has also been shown that this neurogenesis has an age-related decline from preadolescence (8–10 years old) to adulthood (30–35 years old) in humans.

A brain region that supports neurogenesis is classified as neurogenic. Neurogenic implies the presence of immature precursor cells and a microenvironment that is permissive for the production of new neurons. In the adult mammalian brain, there are two neurogenic regions that are generally accepted, the olfactory system and the hippocampus

What relates adult neurogenesis in the hippocampus to depression?

  • The neurogenic hypothesis postulates that a reduced production of new neurons in the hippocampus relates to the pathogenesis of depression and that successful antidepressant treatment requires an enhancement in hippocampal neurogenesis
  • Preclinical evidence has shown that stress suppresses hippocampal neurogenesis
  • Clinically, stressful life events are known to precipitate depression in vulnerable individuals
  • About half of the patients suffering from depression have dysregulation of the HPA system of which the hippocampus is an important part
  • Most antidepressant treatments elevate hippocampal neurogenesis only following chronic administration, which parallels the time-course of the emergence of clinical therapeutic effects
  • Impaired declarative learning and memory and diminished cognitive flexibility is apparent in patients suffering from depression
  • Magnetic resonance imaging showed that depressed individuals have reduced hippocampal volume with the magnitude of the atrophy related to the frequency of the depressive episodes and the duration for which the depression went untreated
  • Although hippocampal neurogenesis might not be involved in the pathogenesis of depression, it might be important for some of the therapeutic effects of antidepressant treatments
  • The several week delay in the therapeutic onset of antidepressant treatment coincides with the maturation time of newly born hippocampal neurons and that is one reason for believing that adult hippocampal neurogenesis is a possible substrate for the actions of antidepressants
  • Other treatments that have antidepressant effect, such as exercise and environmental enrichment, also increase hippocampal neurogenesis
  • Antidepressant treatments blocked the reductions in hippocampal neurogenesis caused by stress

The authors of this extensive review summarize the neurogenesis of hippocampus on a cell level as:

Neurogenesis could serve to increase the number of dentate granule cells, provide a reservoir of highly plastic immature neurons, generate multiple cell types, and/or drive the turnover and replacement of mature granule cells The role adult neurogenesis plays in hippocampal function and disease etiology will begin to be more understood as more selective, inducible, and reversible manipulations of in vivo neurogenesis are developed. The discovery of novel therapeutic compounds for various diseases may involve mechanisms that induce a superior regulation of adult hippocampal neurogenesis

The key question is how changes in neurogenesis may be translated into changes in affective behavior that could be beneficial in treating depression.

Darrick T. Balu, Irwin Lucki (2009). Adult hippocampal neurogenesis: Regulation, functional implications, and contribution to disease pathology Neuroscience & Biobehavioral Reviews, 33 (3), 232-252 DOI: 10.1016/j.neubiorev.2008.08.007