The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Haploview: analysis and visualization of LD and haplotype maps
Barrett, J. C., Fry, B., Maller, J., & Daly, M. J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth457 · Cited by 14,551
Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene
Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., McClay, J., Mill, J., Martin, J., Braithwaite, A., et al. (2003) · Science · doi:10.1126/science.1083968 · Cited by 8,120
Role of genotype in the cycle of violence in maltreated children
Caspi, A., McClay, J., Moffitt, T. E., Mill, J., Martin, J., Craig, I. W., Taylor, A., & Poulton, R. (2002) · Science · doi:10.1126/science.1072290 · Cited by 4,842
A Comparison of Bayesian Methods for Haplotype Reconstruction from Population Genotype Data
Stephens, M., & Donnelly, P. (2003) · The American Journal of Human Genetics · doi:10.1086/379378 · Cited by 3,516
Templeton, A. R., Crandall, K. A., & Sing, C. F. (1992) · Genetics · doi:10.1093/genetics/132.2.619 · Cited by 3,319
Serotonin transporter genetic variation and the response of the human amygdala.
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M. F., & Weinberger, D. R. (2002) · Science · doi:10.1126/science.1071829 · Cited by 2,340
Self-citationTatemoto, K., Carlquist, M., & Mutt, V. (1982) · Nature · doi:10.1038/296659a0 · Cited by 2,254
STRESS AND HIPPOCAMPAL PLASTICITY
McEwen, B. S. (1999) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.22.1.105 · Cited by 2,087
Pezawas, L., Meyer-Lindenberg, A., Drabant, E. M., Verchinski, B. A., Munoz, K. E., Kolachana, B. S., Egan, M. F., Mattay, V. S., Hariri, A. R., & Weinberger, D. R. (2005) · Nature Neuroscience · doi:10.1038/nn1463 · Cited by 1,980
Self-citationAllostasis and Allostatic Load Implications for Neuropsychopharmacology
McEwen, B. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(99)00129-3 · Cited by 1,833
Cited by
Sorted by citations
Biological studies of post-traumatic stress disorder
Pitman, R. K., Rasmusson, A. M., Koenen, K. C., Shin, L. M., Orr, S. P., Gilbertson, M. W., Milad, M. R., & Liberzon, I. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3339 · Cited by 1,529
Reich, J. W., Zautra, A., & Hall, J. S. (2010) · Cited by 1,291
Psychobiology and molecular genetics of resilience
Feder, A., Nestler, E. J., & Charney, D. S. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2649 · Cited by 1,272
Russo, S. J., Murrough, J. W., Han, M.-H., Charney, D. S., & Nestler, E. J. (2012) · Nature Neuroscience · doi:10.1038/nn.3234 · Cited by 1,206
Wu, G., Feder, A., Cohen, H., Kim, J. J., Calderon, S., Charney, D. S., & Mathé, A. A. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00010 · Cited by 887
Metadata
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
