Genetic variation in human NPY expression affects stress response and emotion
Open accessAbstract
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.
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Human genetic studies weakly implicate variations in the NPY gene in emotional behavior and stress responses.
“tentative human genetic studies that weakly implicate variations in the NPY gene in emotional behavior and stress responses (discussed below)20, 21.”
From Neurobiology of resilience (2012) · cites this paper as [20]
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- Authors
- Zhou, Z., Zhu, G., Hariri, A. R., Enoch, M.-A., Scott, D., Sinha, R., Virkkunen, M., Mash, D. C., Lipsky, R. H., Hu, X.-Z., Hodgkinson, C. A., Xu, K., Buzas, B., Yuan, Q., Shen, P.-H., Ferrell, R. E., Manuck, S. B., Brown, S. M., Hauger, R. L., Stohler, C. S., Zubieta, J.-K., & Goldman, D.
- Affiliations
- National Institutes of Health (US)
- University of Pittsburgh (US)
- University of Michigan (US)
- Yale University (US)
- University of Helsinki (FI)
- University of Miami (US)
- University of California San Diego (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Goldman, David
- ORCID
- Venue
- Nature
- Published
- 2008-04
- Volume
- 452
- Issue
- 7190
- Pages
- 997-1001
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC2715959
- OpenAlex
- W1981364522
- Cited by
- 455
- References
- 36
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 9 · 2023: 11 · 2022: 12 · 2021: 22 · 2020: 13 · 2019: 17 · 2018: 24 · 2017: 17 · 2016: 28 · 2015: 29 · 2014: 35 · 2013: 34 · 2012: 39
- FWCI
- 19.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (Z99‐AA999999)
- National Institute on Alcohol Abuse and Alcoholism (Z01AA000301, R01AA013892, R01-AA-13892)
- National Heart, Lung, and Blood Institute (R01HL065137, P01HL040962)
- National Institute of Mental Health (R01MH074697, K01MH072837)
- National Institute on Drug Abuse (K02 DA17232, P50DA016556, K02DA017232, R01DA016423, PL1DA024859, P50-DA16556)
- National Institute of Dental and Craniofacial Research (R01DE015396, R01 DE 15396)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- neuropeptide Y, genetic variation, haplotypes, stress response, psychological resilience, trait anxiety, amygdala activation, endogenous opioid system, limbic system, individual differences
- MeSH terms
- Alleles, Anxiety, Anxiety Disorders, Brain, Emotions, Facial Expression, Finland, Gene Expression Regulation, Haplotypes, Humans, Lymphocytes, Magnetic Resonance Imaging, Male, Neuropeptide Y, Pain, RNA, Messenger, Stress, Physiological, United States, Genetic Variation, Opioid Peptides, Polymorphism, Single Nucleotide, White People
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