Journal
NEUROBIOLOGY OF DISEASE
Volume 52, Issue -, Pages 12-23Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2012.05.007
Keywords
Intermediate phenotype; Depression; Fmri; Gene; Dopamine; Reward; Stress; CRH; HPA axis
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Funding
- NIDA [P30 DA023026]
- ANT North America Inc. (Advanced Neuro Technology)
- AstraZeneca
- Shire
- Ono PharmaUSA
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Major depressive disorder (MDD) is etiologically complex and has a heterogeneous presentation. This heterogeneity hinders the ability of molecular genetic research to reliably detect the small effects conferred by common genetic variation. As a result, significant research efforts have been directed at investigating more homogenous intermediate phenotypes believed to be more proximal to gene function and lie between genes and/or environmental effects and disease processes. In the current review we survey and integrate research on two promising intermediate phenotypes linked to depression: reward processing and stress sensitivity. A synthesis of this burgeoning literature indicates that a molecular genetic approach focused on intermediate phenotypes holds significant promise to fundamentally improve our understanding of the pathophysiology and etiology of depression, which will be required for improved diagnostic definitions and the development of novel and more efficacious treatment and prevention strategies. We conclude by highlighting challenges facing intermediate phenotype research and future development that will be required to propel this pivotal research into new directions. (C) 2012 Elsevier Inc. All rights reserved.
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