Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder

Rongwei Zhai; Geya Tong; Zheqin Li; Weichen Song; Yang Hu; Sha Xu; Qiqi Wei; Xiaocheng Zhang; Yi Li; Bingbing Liao; Chenyu Yuan; Yinqing Fan; Ge Song; Yinyin Ouyang; Wenxuan Zhang; Yaqiu Tang; Minghui Jin; Yuxian Zhang; He Li; Zhi Yang; Guan Ning Lin; Dan J Stein; Zhi-Qi Xiong; Zhen Wang

doi:10.1093/nsr/nwad312

Rhesus monkeys exhibiting spontaneous ritualistic behaviors resembling obsessive-compulsive disorder

Natl Sci Rev. 2023 Dec 8;10(11):nwad312. doi: 10.1093/nsr/nwad312. eCollection 2023 Nov.

Authors

Rongwei Zhai^{1

2

3

4}, Geya Tong¹, Zheqin Li¹, Weichen Song¹, Yang Hu¹, Sha Xu^{2

3}, Qiqi Wei^{2

3}, Xiaocheng Zhang^{2

3}, Yi Li¹, Bingbing Liao¹, Chenyu Yuan¹, Yinqing Fan¹, Ge Song¹, Yinyin Ouyang¹, Wenxuan Zhang¹, Yaqiu Tang¹, Minghui Jin¹, Yuxian Zhang², He Li², Zhi Yang¹, Guan Ning Lin¹, Dan J Stein⁵, Zhi-Qi Xiong^{2

4}, Zhen Wang^{1

6}

Affiliations

¹ Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
² Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
³ Lingang Laboratory, Shanghai 200031, China.
⁴ Shanghai Center for Brain Science and Brain-Inspired Technology, Shanghai 201602, China.
⁵ Translational Neuropsychiatry Unit (TNU), Department of Clinical Medicine, Aarhus University, Aarhus 8200, Denmark.
⁶ Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Abstract

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric disorder that affects ∼2%-3% of the population globally. Studying spontaneous OCD-like behaviors in non-human primates may improve our understanding of the disorder. In large rhesus monkey colonies, we found 10 monkeys spontaneously exhibiting persistent sequential motor behaviors (SMBs) in individual-specific sequences that were repetitive, time-consuming and stable over prolonged periods. Genetic analysis revealed severely damaging mutations in genes associated with OCD risk in humans. Brain imaging showed that monkeys with SMBs had larger gray matter (GM) volumes in the left caudate nucleus and lower fractional anisotropy of the corpus callosum. The GM volume of the left caudate nucleus correlated positively with the daily duration of SMBs. Notably, exposure to a stressor (human presence) significantly increased SMBs. In addition, fluoxetine, a serotonergic medication commonly used for OCD, decreased SMBs in these monkeys. These findings provide a novel foundation for developing better understanding and treatment of OCD.

Keywords: OCD risk genes; caudate nucleus; fluoxetine; obsessive-compulsive disorder (OCD); primate ritualistic behavior model.