TY - JOUR
T1 - The neurogenesis hypothesis of affective and anxiety disorders
T2 - Are we mistaking the scaffolding for the building?
AU - Petrik, David
AU - Lagace, Diane C.
AU - Eisch, Amelia J.
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health ( R01 DA016765 and K02 DA023555 to AJE), NASA ( NNX07AP84G to AJE), NSERC ( 371716 to DCL), a Young Investigator Award (DCL) and an Independent Investigator Award (AJE) from the National Alliance for Research on Schizophrenia and Depression, and a postdoctoral research fellowship from the Canadian Institute of Health Research (DCL). Special thanks to Dr. Jason Snyder for permission to use his blog ( http://www.functionalneurogenesis.com/blog/ ) as inspiration for Tables 1 and 2 of this review.
PY - 2012/1
Y1 - 2012/1
N2 - 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. This article is part of a special Issue entitled 'Anxiety and Depression'.
AB - 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. This article is part of a special Issue entitled 'Anxiety and Depression'.
KW - Adult neurogenesis
KW - Anxiety
KW - Dentate gyrus
KW - Depression
KW - Hippocampus
KW - Post-traumatic stress disorder
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U2 - 10.1016/j.neuropharm.2011.09.003
DO - 10.1016/j.neuropharm.2011.09.003
M3 - Article
C2 - 21945290
AN - SCOPUS:80054118405
SN - 0028-3908
VL - 62
SP - 21
EP - 34
JO - Neuropharmacology
JF - Neuropharmacology
IS - 1
ER -