title: Macaques exhibit a naturally-occurring depression similar to humans.
abstract: Rodent models have dominated preclinical investigations into the mechanisms of depression. However, these models-which rely on subjecting individual rodents to physical stressors - do not realistically resemble the etiopathological development of depression, which occurs naturally in a social context. A non-human primate model that better reflects the social ethological aspects of depression would be more advantageous to investigating pathophysiological mechanisms and developing antidepressant therapeutics. Here, we describe and model a naturally-occurring depressive state in a non-human primate species, the cynomolgus monkey (Macaca fascicularis), in a realistic social ethological context and associate the depressed behavioral phenotype with significant serum metabolic perturbations. One to two subjects per stable social colony (17-22 subjects) manifested a depressive phenotype that may be attributed to psychosocial stress. In accordance with rodent and human studies, the serum metabolic phenotype of depressed and healthy subjects significantly differed, supporting the model's face validity. However, application of the fast-acting antidepressant ketamine failed to demonstrate predictive validity. This study proposes a non-human primate depression model in a realistic social ethological context that can better approximate the psychosocial stressors underlying depression.
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Xu
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China [3] Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Wu
authors.affiliation: 1] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China [2] Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 1] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China [2] Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zheng
authors.affiliation: 1] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China [2] Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Qinmin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Yongjia
authors.initials: Y
authors.lastname: Ji
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: 1] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China [2] Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Fang
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Deyu
authors.initials: D
authors.lastname: Yang
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China.
authors.forename: Narayan D
authors.initials: ND
authors.lastname: Melgiri
authors.affiliation: Department of Pathology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Carol
authors.initials: C
authors.lastname: Shively
authors.affiliation: 1] Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing, China [2] Institute of Neuroscience, Chongqing Medical University and the Chongqing Key Laboratory of Neurobiology, Chongqing, China [3] Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003866:Depressive Disorder / Q000503:physiopathology*; D016002:Discriminant Analysis; D004195:Disease Models, Animal; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007649:Ketamine / Q000494:pharmacology; D016018:Least-Squares Analysis; D008251:Macaca; D008297:Male; D055442:Metabolome; D010641:Phenotype
chemical_list: D007649:Ketamine