Publication Type Academic Article
Authors Li A, Jing D, Dellarco D, Hall B, Yang R, Heilberg R, Huang C, Liston C, Casey B, Lee F
Journal Mol Psychiatry
Volume 26
Issue 3
Pagination 955-973
Date Published 04/16/2019
ISSN 1476-5578
Keywords Brain-Derived Neurotrophic Factor, Polymorphism, Single Nucleotide
Abstract Social deficits are common in many psychiatric disorders. However, due to inadequate tools for manipulating circuit activity in humans and unspecific paradigms for modeling social behaviors in rodents, our understanding of the molecular and circuit mechanisms mediating social behaviors remains relatively limited. Using human functional neuroimaging and rodent fiber photometry, we identified a mOFC-BLA projection that modulates social approach behavior and influences susceptibility to social anxiety. In humans and knock-in mice with a loss of function BDNF SNP (Val66Met), the functionality of this circuit was altered, resulting in social behavioral changes in human and mice. We further showed that the development of this circuit is disrupted in BDNF Met carriers due to insufficient BDNF bioavailability, specifically during a peri-adolescent timeframe. These findings define one mechanism by which social anxiety may stem from altered maturation of orbitofronto-amygdala projections and identify a developmental window in which BDNF-based interventions may have therapeutic potential.
DOI 10.1038/s41380-019-0422-4
PubMed ID 30992540
PubMed Central ID PMC6883137
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