Genetic variation in human NPY expression affects stress response and emotion.

Journal Article (Journal Article)

Understanding inter-individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y (NPY) is anxiolytic and its release is induced by stress. NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories. Here we show that haplotype-driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in post-mortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype-driven NPY expression predicted higher emotion-induced activation of the amygdala, as well as diminished resiliency as assessed by pain/stress-induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism (SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter-individual variation in resiliency to stress, a risk factor for many diseases.

Full Text

Duke Authors

Cited Authors

  • Zhou, Z; Zhu, G; Hariri, AR; Enoch, M-A; Scott, D; Sinha, R; Virkkunen, M; Mash, DC; Lipsky, RH; Hu, X-Z; Hodgkinson, CA; Xu, K; Buzas, B; Yuan, Q; Shen, P-H; Ferrell, RE; Manuck, SB; Brown, SM; Hauger, RL; Stohler, CS; Zubieta, J-K; Goldman, D

Published Date

  • April 2008

Published In

Volume / Issue

  • 452 / 7190

Start / End Page

  • 997 - 1001

PubMed ID

  • 18385673

Pubmed Central ID

  • PMC2715959

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature06858


  • eng