Patrick H Roseboom1, Steven A Nanda2, Andrew S Fox3, Jonathan A Oler4, Alexander J Shackman5, Steven E Shelton2, Richard J Davidson6, Ned H Kalin7. 1. Department of Psychiatry , University of Wisconsin at Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin at Madison, Madison, Wisconsin. Electronic address: roseboom@wisc.edu. 2. Department of Psychiatry , University of Wisconsin at Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin at Madison, Madison, Wisconsin. 3. Department of Psychiatry , University of Wisconsin at Madison, Madison, Wisconsin; Department of Psychology, University of Wisconsin at Madison, Madison, Wisconsin; Center for Investigating Healthy Minds, University of Wisconsin at Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin at Madison, Madison, Wisconsin; Lane Neuroimaging Laboratory, University of Wisconsin at Madison, Madison, Wisconsins; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin at Madison, Madison, Wisconsin. 4. Department of Psychiatry , University of Wisconsin at Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin at Madison, Madison, Wisconsin; Lane Neuroimaging Laboratory, University of Wisconsin at Madison, Madison, Wisconsins. 5. Department of Psychology, Maryland Neuroimaging Center and the Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland. 6. Department of Psychiatry , University of Wisconsin at Madison, Madison, Wisconsin; Department of Psychology, University of Wisconsin at Madison, Madison, Wisconsin; Center for Investigating Healthy Minds, University of Wisconsin at Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin at Madison, Madison, Wisconsin; Waisman Laboratory for Brain Imaging and Behavior, University of Wisconsin at Madison, Madison, Wisconsin. 7. Department of Psychiatry , University of Wisconsin at Madison, Madison, Wisconsin; Department of Psychology, University of Wisconsin at Madison, Madison, Wisconsin; Center for Investigating Healthy Minds, University of Wisconsin at Madison, Madison, Wisconsin; HealthEmotions Research Institute, University of Wisconsin at Madison, Madison, Wisconsin; Lane Neuroimaging Laboratory, University of Wisconsin at Madison, Madison, Wisconsins.
Abstract
BACKGROUND: Anxious temperament (AT) is identifiable early in life and predicts the later development of anxiety disorders and depression. Neuropeptide Y (NPY) is a putative endogenous anxiolytic neurotransmitter that adaptively regulates responses to stress and might confer resilience to stress-related psychopathology. With a well-validated nonhuman primate model of AT, we examined expression of the NPY system in the central nucleus (Ce) of the amygdala, a critical neural substrate for extreme anxiety. METHODS: In 24 young rhesus monkeys, we measured Ce messenger RNA (mRNA) levels of all members of the NPY system that are detectable in the Ce with quantitative real time polymerase chain reaction. We then examined the relationship between these mRNA levels and both AT expression and brain metabolism. RESULTS: Lower mRNA levels of neuropeptide Y receptor 1 (NPY1R) and NPY5R but not NPY or NPY2R in the Ce predicted elevated AT; mRNA levels for NPY1R and NPY5R in the motor cortex were not related to AT. In situ hybridization analysis provided for the first time a detailed description of NPY1R and NPY5R mRNA distribution in the rhesus amygdala and associated regions. Lastly, mRNA levels for these two receptors in the Ce predicted metabolic activity in several regions that have the capacity to regulate the Ce. CONCLUSIONS: Decreased NPY signaling in the Ce might contribute to the altered metabolic activity that is a component of the neural substrate underlying AT. This suggests that enhancement of NPY signaling might reduce the risk to develop psychopathology.
BACKGROUND: Anxious temperament (AT) is identifiable early in life and predicts the later development of anxiety disorders and depression. Neuropeptide Y (NPY) is a putative endogenous anxiolytic neurotransmitter that adaptively regulates responses to stress and might confer resilience to stress-related psychopathology. With a well-validated nonhuman primate model of AT, we examined expression of the NPY system in the central nucleus (Ce) of the amygdala, a critical neural substrate for extreme anxiety. METHODS: In 24 young rhesus monkeys, we measured Ce messenger RNA (mRNA) levels of all members of the NPY system that are detectable in the Ce with quantitative real time polymerase chain reaction. We then examined the relationship between these mRNA levels and both AT expression and brain metabolism. RESULTS: Lower mRNA levels of neuropeptide Y receptor 1 (NPY1R) and NPY5R but not NPY or NPY2R in the Ce predicted elevated AT; mRNA levels for NPY1R and NPY5R in the motor cortex were not related to AT. In situ hybridization analysis provided for the first time a detailed description of NPY1R and NPY5R mRNA distribution in the rhesus amygdala and associated regions. Lastly, mRNA levels for these two receptors in the Ce predicted metabolic activity in several regions that have the capacity to regulate the Ce. CONCLUSIONS: Decreased NPY signaling in the Ce might contribute to the altered metabolic activity that is a component of the neural substrate underlying AT. This suggests that enhancement of NPY signaling might reduce the risk to develop psychopathology.
Authors: Ramon O Tasan; Ngoc Khoi Nguyen; Stefan Weger; Simone B Sartori; Nicolas Singewald; Regine Heilbronn; Herbert Herzog; Günther Sperk Journal: J Neurosci Date: 2010-05-05 Impact factor: 6.167
Authors: Andrew S Fox; Jonathan A Oler; Steven E Shelton; Steven A Nanda; Richard J Davidson; Patrick H Roseboom; Ned H Kalin Journal: Proc Natl Acad Sci U S A Date: 2012-10-15 Impact factor: 11.205
Authors: Michael J Hawrylycz; Ed S Lein; Angela L Guillozet-Bongaarts; Elaine H Shen; Lydia Ng; Jeremy A Miller; Louie N van de Lagemaat; Kimberly A Smith; Amanda Ebbert; Zackery L Riley; Chris Abajian; Christian F Beckmann; Amy Bernard; Darren Bertagnolli; Andrew F Boe; Preston M Cartagena; M Mallar Chakravarty; Mike Chapin; Jimmy Chong; Rachel A Dalley; Barry David Daly; Chinh Dang; Suvro Datta; Nick Dee; Tim A Dolbeare; Vance Faber; David Feng; David R Fowler; Jeff Goldy; Benjamin W Gregor; Zeb Haradon; David R Haynor; John G Hohmann; Steve Horvath; Robert E Howard; Andreas Jeromin; Jayson M Jochim; Marty Kinnunen; Christopher Lau; Evan T Lazarz; Changkyu Lee; Tracy A Lemon; Ling Li; Yang Li; John A Morris; Caroline C Overly; Patrick D Parker; Sheana E Parry; Melissa Reding; Joshua J Royall; Jay Schulkin; Pedro Adolfo Sequeira; Clifford R Slaughterbeck; Simon C Smith; Andy J Sodt; Susan M Sunkin; Beryl E Swanson; Marquis P Vawter; Derric Williams; Paul Wohnoutka; H Ronald Zielke; Daniel H Geschwind; Patrick R Hof; Stephen M Smith; Christof Koch; Seth G N Grant; Allan R Jones Journal: Nature Date: 2012-09-20 Impact factor: 49.962
Authors: Alexander J Shackman; Do P M Tromp; Melissa D Stockbridge; Claire M Kaplan; Rachael M Tillman; Andrew S Fox Journal: Psychol Bull Date: 2016-10-10 Impact factor: 17.737
Authors: Ned H Kalin; Andrew S Fox; Rothem Kovner; Marissa K Riedel; Eva M Fekete; Patrick H Roseboom; Do P M Tromp; Benjamin P Grabow; Miles E Olsen; Ethan K Brodsky; Daniel R McFarlin; Andrew L Alexander; Marina E Emborg; Walter F Block; Julie L Fudge; Jonathan A Oler Journal: Biol Psychiatry Date: 2016-01-30 Impact factor: 13.382
Authors: Bin Qiu; Richard L Bell; Yong Cao; Lingling Zhang; Robert B Stewart; Tamara Graves; Lawrence Lumeng; Weidong Yong; Tiebing Liang Journal: J Genet Genomics Date: 2016-04-29 Impact factor: 4.275