The neurogenesis hypothesis of affective and anxiety disorders: Are we mistaking the scaffolding for the building?

Petrik, David ORCID: https://orcid.org/0000-0003-3026-0770, Lagace, Diane C. and Eisch, Amelia J. 2012. The neurogenesis hypothesis of affective and anxiety disorders: Are we mistaking the scaffolding for the building? Neuropharmacology 62 (1) , pp. 21-34. 10.1016/j.neuropharm.2011.09.003

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Abstract

Hypotheses are scaffoldings erected in front of a building and then dismantled when the building is finished. They are indispensable for the workman; but you mustn’t mistake the scaffolding for the building. Johann Wolfgang von Goethe. The neurogenesis hypothesis of affective disorders – in its simplest form – postulates that the generation of neurons in the postnatal hippocampal dentate gyrus is involved in the etiology and treatment efficacy of major depressive disorder (MDD). The hypothesis was established in the 1990s but was built on a broad foundation of earlier research on the hippocampus, serotonin and MDD. It has gone through several growth phases fueled by discoveries both correlative and causative in nature. Recently, the hypothesis has also been broadened to also include potential relevance for anxiety disorders, like post-traumatic stress disorder (PTSD). As any hypothesis should be, it has been tested and challenged, sometimes vigorously. Here we review the current standing of the neurogenesis hypothesis of affective and anxiety disorders, noting in particular how a central postulate – that decreased neurogenesis results in depression or anxiety – has, in general, been rejected. We also review the controversies on whether treatments for these disorders, like antidepressants, rely on intact neurogenesis for their efficacy, and the existence of neurogenesis-dependent and -independent effects of antidepressants. In addition, we review the implications that the hypothesis has for the response to stress, PTSD, and the neurobiology of resilience, and highlight our own work showing that adult-generated neurons are functionally important for the behavioral response to social stress. We conclude by emphasizing how advancements in transgenic mouse technology, rodent behavioral analyses, and our understanding of the neurogenesis process will allow us to refine our conclusions and perform ever more specific experiments. Such scrutiny is critical, since if we “mistake the scaffolding for the building” we could overlook opportunities for translational impact in the clinic.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Elsevier
ISSN:	0028-3908
Date of Acceptance:	6 September 2011
Last Modified:	26 Oct 2022 07:37
URI:	https://orca.cardiff.ac.uk/id/eprint/125345

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