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

@article{citeulike:2626756, abstract = {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 anxiolytic1, 2 and its release is induced by stress3. 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 memories4, 5, 6. 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.}, author = {Zhou, Zhifeng and Zhu, Guanshan and Hariri, Ahmad R. and Enoch, Mary-Anne and Scott, David and Sinha, Rajita and Virkkunen, Matti and Mash, Deborah C. and Lipsky, Robert H. and Hu, Xian-Zhang and Hodgkinson, Colin A. and Xu, Ke and Buzas, Beata and Yuan, Qiaoping and Shen, Pei-Hong and Ferrell, Robert E. and Manuck, Stephen B. and Brown, Sarah M. and Hauger, Richard L. and Stohler, Christian S. and Zubieta, Jon-Kar and Goldman, David}, citeulike-article-id = {2626756}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/nature06858}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/nature06858}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18385673}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18385673}, day = {02}, doi = {10.1038/nature06858}, issn = {0028-0836}, journal = {Nature}, keywords = {amygdala, snp, stress}, month = {April}, number = {7190}, pages = {997--1001}, posted-at = {2008-04-23 21:11:53}, priority = {2}, publisher = {Nature Publishing Group}, title = {Genetic variation in human NPY expression affects stress response and emotion}, url = {http://dx.doi.org/10.1038/nature06858}, volume = {452}, year = {2008} }

TY - JOUR ID - citeulike:2626756 L3 - citeulike-article-id:2626756 N2 - 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 anxiolytic1, 2 and its release is induced by stress3. 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 memories4, 5, 6. 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. IS - 7190 JF - Nature SN - 0028-0836 EP - 1001 TI - Genetic variation in human NPY expression affects stress response and emotion PB - Nature Publishing Group VL - 452 SP - 997 KW - amygdala KW - snp KW - stress AU - Zhou, Zhifeng AU - Zhu, Guanshan AU - Hariri, Ahmad AU - Enoch, Mary-Anne AU - Scott, David AU - Sinha, Rajita AU - Virkkunen, Matti AU - Mash, Deborah AU - Lipsky, Robert AU - Hu, Xian-Zhang AU - Hodgkinson, Colin AU - Xu, Ke AU - Buzas, Beata AU - Yuan, Qiaoping AU - Shen, Pei-Hong AU - Ferrell, Robert AU - Manuck, Stephen AU - Brown, Sarah AU - Hauger, Richard AU - Stohler, Christian AU - Zubieta, Jon-Kar AU - Goldman, David PY - 2008/04/02/ UR - http://dx.doi.org/10.1038/nature06858 ER -