A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques

Nonsuicidal self-injury (NSSI) demonstrates escalating prevalence among adolescents as a maladaptive behavior characterized by deliberate self-harm, yet its neurobiological underpinnings remain elusive. Spontaneous self-injurious behavior (SIB) in nonhuman primates (NHPs) emerges as a clinically rel...

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Main Authors: Ya-Li Zhang, Yi-Cheng Qiao, Yun-Chao Ji, Hong-Di Huang, Long Zhang, Jian-Xiong Ruan, Chen-Yao Li, Hui-Heng Xie, Bao-Lin Zhang, Qi Zhou, Sha-Sha Yue, Xiao-Mei Yu, Ming-Hao Qiu, Chuan-Kai Yu, Si-Chu Wu, Yu-Fang Zhou, Yan-Ling Li, Hong-Mei Zhu, Shu-Zhen Dong, Kang Huang, Yun Wang, Qiong Wang, Yi-Jiang Li, Ya Xie, Hui-Ling Chen, Long-Bao Lv, Shu Liu, Yong-Gang Yao, Chun Wang, Ning Liu, Jian-Hong Wang
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0782
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author Ya-Li Zhang
Yi-Cheng Qiao
Yun-Chao Ji
Hong-Di Huang
Long Zhang
Jian-Xiong Ruan
Chen-Yao Li
Hui-Heng Xie
Bao-Lin Zhang
Qi Zhou
Sha-Sha Yue
Xiao-Mei Yu
Ming-Hao Qiu
Chuan-Kai Yu
Si-Chu Wu
Yu-Fang Zhou
Yan-Ling Li
Hong-Mei Zhu
Shu-Zhen Dong
Kang Huang
Yun Wang
Qiong Wang
Yi-Jiang Li
Ya Xie
Hui-Ling Chen
Long-Bao Lv
Shu Liu
Yong-Gang Yao
Chun Wang
Ning Liu
Jian-Hong Wang
author_facet Ya-Li Zhang
Yi-Cheng Qiao
Yun-Chao Ji
Hong-Di Huang
Long Zhang
Jian-Xiong Ruan
Chen-Yao Li
Hui-Heng Xie
Bao-Lin Zhang
Qi Zhou
Sha-Sha Yue
Xiao-Mei Yu
Ming-Hao Qiu
Chuan-Kai Yu
Si-Chu Wu
Yu-Fang Zhou
Yan-Ling Li
Hong-Mei Zhu
Shu-Zhen Dong
Kang Huang
Yun Wang
Qiong Wang
Yi-Jiang Li
Ya Xie
Hui-Ling Chen
Long-Bao Lv
Shu Liu
Yong-Gang Yao
Chun Wang
Ning Liu
Jian-Hong Wang
author_sort Ya-Li Zhang
collection DOAJ
description Nonsuicidal self-injury (NSSI) demonstrates escalating prevalence among adolescents as a maladaptive behavior characterized by deliberate self-harm, yet its neurobiological underpinnings remain elusive. Spontaneous self-injurious behavior (SIB) in nonhuman primates (NHPs) emerges as a clinically relevant animal model for investigating NSSI pathogenesis and therapeutic interventions. However, previous studies have yet to comprehensively evaluate the translational value of self-injury in NHPs through integrated behavioral and neuroimaging characterization. In this study, we identified spontaneously self-injurious macaques within our NHP colony and performed multimodal assessments encompassing ethological profiling, neuroendocrine assays, metabolomic analysis, and neuroimaging. Our results revealed that SIB macaques exhibited biological patterns and temporal onset sequences of self-harm, accompanied by a locomotor and social interaction decrease based on 3-dimensional deep-learning recognition, sensory processing deficits, and impairments in emotional and cognitive processing. Biochemical profiling demonstrated reduced plasma concentrations of cortisol, serotonin, and oxytocin, coupled with metabolomic disturbances including up-regulation of digestive-related pathways and down-regulation of dopaminergic synaptic signaling and phosphatidylinositol metabolism. Neuroimaging analyses identified structural abnormalities featuring volumetric enlargement in amygdala and midbrain regions alongside gray matter reduction in the frontal and parietal lobes. Enhanced structural and functional connectivity was observed. Network-based statistics highlighted increased functional connectivity primarily between the frontal and parietal lobes. These alterations demonstrated a partial correlation with observed behavioral deficits in the self-injury macaques. Notably, a series of administration of low-dose ketamine had no effect on SIB and the physical index. Our integrative multi-omic approach elucidates the neurobiological phenotype of spontaneous SIB in macaques, highlighting the value of the SIB model for pathogenetic investigation and therapeutic development in human NSSIs.
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spelling doaj-art-66bf845635b9483bbebf7936dac45be82025-08-20T03:56:17ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742025-01-01810.34133/research.0782A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus MacaquesYa-Li Zhang0Yi-Cheng Qiao1Yun-Chao Ji2Hong-Di Huang3Long Zhang4Jian-Xiong Ruan5Chen-Yao Li6Hui-Heng Xie7Bao-Lin Zhang8Qi Zhou9Sha-Sha Yue10Xiao-Mei Yu11Ming-Hao Qiu12Chuan-Kai Yu13Si-Chu Wu14Yu-Fang Zhou15Yan-Ling Li16Hong-Mei Zhu17Shu-Zhen Dong18Kang Huang19Yun Wang20Qiong Wang21Yi-Jiang Li22Ya Xie23Hui-Ling Chen24Long-Bao Lv25Shu Liu26Yong-Gang Yao27Chun Wang28Ning Liu29Jian-Hong Wang30National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.Guangdong Bayone Biotech CO., Ltd., Guangzhou, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.State Key Laboratory of Cognitive Science and Mental Health, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility) and National Resource Center for Non-Human Primates, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.Nonsuicidal self-injury (NSSI) demonstrates escalating prevalence among adolescents as a maladaptive behavior characterized by deliberate self-harm, yet its neurobiological underpinnings remain elusive. Spontaneous self-injurious behavior (SIB) in nonhuman primates (NHPs) emerges as a clinically relevant animal model for investigating NSSI pathogenesis and therapeutic interventions. However, previous studies have yet to comprehensively evaluate the translational value of self-injury in NHPs through integrated behavioral and neuroimaging characterization. In this study, we identified spontaneously self-injurious macaques within our NHP colony and performed multimodal assessments encompassing ethological profiling, neuroendocrine assays, metabolomic analysis, and neuroimaging. Our results revealed that SIB macaques exhibited biological patterns and temporal onset sequences of self-harm, accompanied by a locomotor and social interaction decrease based on 3-dimensional deep-learning recognition, sensory processing deficits, and impairments in emotional and cognitive processing. Biochemical profiling demonstrated reduced plasma concentrations of cortisol, serotonin, and oxytocin, coupled with metabolomic disturbances including up-regulation of digestive-related pathways and down-regulation of dopaminergic synaptic signaling and phosphatidylinositol metabolism. Neuroimaging analyses identified structural abnormalities featuring volumetric enlargement in amygdala and midbrain regions alongside gray matter reduction in the frontal and parietal lobes. Enhanced structural and functional connectivity was observed. Network-based statistics highlighted increased functional connectivity primarily between the frontal and parietal lobes. These alterations demonstrated a partial correlation with observed behavioral deficits in the self-injury macaques. Notably, a series of administration of low-dose ketamine had no effect on SIB and the physical index. Our integrative multi-omic approach elucidates the neurobiological phenotype of spontaneous SIB in macaques, highlighting the value of the SIB model for pathogenetic investigation and therapeutic development in human NSSIs.https://spj.science.org/doi/10.34133/research.0782
spellingShingle Ya-Li Zhang
Yi-Cheng Qiao
Yun-Chao Ji
Hong-Di Huang
Long Zhang
Jian-Xiong Ruan
Chen-Yao Li
Hui-Heng Xie
Bao-Lin Zhang
Qi Zhou
Sha-Sha Yue
Xiao-Mei Yu
Ming-Hao Qiu
Chuan-Kai Yu
Si-Chu Wu
Yu-Fang Zhou
Yan-Ling Li
Hong-Mei Zhu
Shu-Zhen Dong
Kang Huang
Yun Wang
Qiong Wang
Yi-Jiang Li
Ya Xie
Hui-Ling Chen
Long-Bao Lv
Shu Liu
Yong-Gang Yao
Chun Wang
Ning Liu
Jian-Hong Wang
A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques
Research
title A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques
title_full A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques
title_fullStr A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques
title_full_unstemmed A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques
title_short A Study of Spontaneous Self-Injurious Behavior and Neuroimaging in Rhesus Macaques
title_sort study of spontaneous self injurious behavior and neuroimaging in rhesus macaques
url https://spj.science.org/doi/10.34133/research.0782
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