Is neurogenesis relevant in depression and in the mechanism of antidepressant drug action? A critical review

Abstract

Objectives. Major depression is a complex disorder that involves genetic, epigenetic and environmental factors in its aetiology. Recent research has suggested that hippocampal neurogenesis may play a role in antidepressant action. However, careful examination of the literature suggests that the complex biological and psychological changes associated with depression cannot be attributed to disturbance in hippocampal neurogenesis alone. While antidepressants may induce hippocampal neurogenesis in non-human primates, there is a paucity of evidence that such effects are sufficient for full therapeutic action in humans. Methods. This review examines the literature on neurogenesis and discusses the stress-induced cortisol neurotoxicity and antidepressant-induced neurogenesis rescue model of depression. The disparity between a simple antidepressant-induced neurogenesis rescue model in the hippocampus and the complexity of clinical depression is analyzed through critical evaluation of recent research data. Results and conclusions. Major depression is a complex brain disorder with multiple symptoms and disturbances reflecting dysfunction in more than one single brain area. Initial research suggesting a model of hippocampal degeneration as basis of depression, and reversal by antidepressants through neurogenesis seems to be over-simplified given the emergence of new data. Synaptogenesis and re-organization or re-integration of new neurons rather than simple addition of new neurons may underlie the role of antidepressant drugs in the reversal of some but not all symptoms in depression. The importance of the neurogenesis hypothesis of depression and antidepressant action lies in stimulating further research into the possible roles played by the new neurons and synapses generated.

Key words::

• Antidepressants
• depression
• neurogenesis
• synaptogenesis
• stress

Acknowledgements

None.

Statement of Interest

No funding received for the study. Professor Tang has received travel support and grants from Lundbeck, Eli Lilly and Otsuka.