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Eur Neuropsychopharmacol. 2017 Jun;27(6):543-553. doi: 10.1016/j.euroneuro.2017.03.004. Epub 2017 May 11.

Mechanisms underlying the early risk to develop anxiety and depression: A translational approach.

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Department of Psychiatry, HealthEmotions Research Institute, University of Wisconsin, Madison, United States. Electronic address:


Anxious temperament (AT) is an early life disposition that markedly increases the risk to develop stress related psychopathology such as anxiety and depressive disorders. Since anxiety and depression are common, and frequently have their onset early in life, a better understanding of the factors related to their childhood onset will facilitate the development of new more effective neurally informed interventions. A nonhuman primate (NHP) developmental model of childhood AT has been established, which has provided an understanding of the neural systems and molecular mechanisms mediating the development of AT. Multimodal neuroimaging studies reveal altered brain metabolism across prefrontal, limbic (e.g. central nucleus of the amygdala (Ce) and anterior hippocampus), and brainstem regions, as well as altered functional connectivity involving the Ce. Heritability studies demonstrate that individual variation in AT is heritable, and genetic correlational analyses demonstrate that metabolism in the posterior orbital frontal cortex, the bed nucleus of the stria terminalis, and the periaqueductal gray share a genetic substrate with AT. On a molecular level, the finding of reduced expression of Ce neuroplasticity genes provides the basis for a neurodevelopmental hypothesis focused on the Ce. Viral vector methods for altering gene expression in the Ce of young NHPs are currently being used as a prelude to conceptualizing novel molecularly targeted early life interventions.

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