Anatomic alterations across amygdala subnuclei in medication-free patients with obsessive–compulsive disorder

Anatomic alterations across amygdala subnuclei in medication-free patients with obsessive–compulsive disorder

J Psychiatry Neurosci 2020;45(5):334-343 | PDF | Appendix

Lianqing Zhang, PhD*; Xinyu Hu, PhD*; Lu Lu, MM; Bin Li, MD; Xiaoxiao Hu, MM; Xuan Bu, PhD; Hailong Li, PhD; Shi Tang, MM; Yingxue Gao, MM; Yanchun Yang, PhD; John A. Sweeney, PhD; Qiyong Gong, MD, PhD; Xiaoqi Huang, MD, PhD

Background: The amygdala has been implicated in obsessive–compulsive disorder (OCD), a common, disabling illness. However, the regional distribution of anatomic alterations in this structure and their association with the symptoms of OCD remains to be established.

Methods: We collected high-resolution 3D T1-weighted images from 81 untreated patients with OCD and no lifetime history of comorbid psychotic, affective or anxiety disorders, and from 95 age- and sex-matched healthy controls. We extracted the volume of the central nucleus of the amygdala (CeA) and the basolateral complex of the amygdala (BLA) and compared them across groups using FreeSurfer 6.0. In exploratory analyses, we evaluated other subnuclei, including the cortical medial nuclei, the anterior amygdaloid area, and the corticoamygdaloid transition area.

Results: Patients with OCD had reduced amygdala volume bilaterally compared with healthy controls (left, p = 0.034; right, p = 0.002). Volume reductions were greater in the CeA (left: −11.9%, p = 0.002; right: −13.3%, p < 0.001) than in the BLA (left lateral nucleus: −3.3%, p = 0.029; right lateral nucleus: −3.9%, p = 0.018; right basal nucleus: −4.1%, p = 0.017; left accessory basal nucleus: −6.5%, p = 0.001; right accessory basal nucleus: −9.3%, p < 0.001). Volume reductions in the CeA were associated with illness duration. Exploratory analysis revealed smaller medial (left: −15.4%, p < 0.001, η2 = 0.101) and cortical (left: −9.1%, p = 0.001, η2 = 0.058; right: −15.4%, p < 0.001, η2 = 0.175) nuclei in patients with OCD compared with healthy controls.

Limitations: Although the strict exclusion criteria used in the study helped us to identify OCD-specific alterations, they may have limited generalizability to the broader OCD population.

Conclusion: Our results provide a comprehensive anatomic profile of alterations in the amygdala subnuclei in untreated patients with OCD and highlight a distinctive pattern of volume reductions across subnuclei in OCD. Based on the functional properties of the amygdala subnuclei established from preclinical research, CeA impairment may contribute to behavioural inflexibility, and BLA disruption may be responsible for altered fear conditioning and the affective components of OCD.


Submitted June 14, 2019; Revised Oct. 12, 2019; Accepted Dec. 23, 2019; Published online Apr. 15, 2020

*These authors contributed equally to this work.

Acknowledgements: This study was supported by the National Natural Science Foundation (Grant No. 81671669, 81621003, 814111130163, 81761128023 and 81820108018) and Youth Technology Grant of Sichuan Province (No 2017JQ0001), by an award from the Humboldt Foundation to J. Sweeney, and by the Program for Changjiang Scholars and Innovative Research Team in University (PCSIRT, Grant No. IRT16R52) of China. Q. Gong acknowledges support from his Changjiang Scholar Professorship Award (Award No. T2014190) of China and American CMB Distinguished Professorship Award (Award No. F510000/ G16916411) administered by the Institute of International Education, USA.

Affiliations: From the Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, China (Zhang, Xinyu Hu, Lu, Xiaoxiao Hu, Bu, Li, Tang, Gao, Sweeney, Gong, Huang); the Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, PR China (Li, Yang); the Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, USA (Sweeney); and the Psychoradiology Research Unit of the Chinese Academy of Medical Sciences (2018RU011), West China Hospital of Sichuan University, Chengdu, Sichuan, China (Zhang, Xinyu Hu, Lu, Xiaoxiao Hu, Bu, Li, Tang, Gao, Gong, Huang).

Competing interests: None declared.

Contributors: L. Zhang, Xinyu Hu, X. Bu, Y. Yang, Q. Gong and X. Huang designed the study. Xinyu Hu and Y. Yang acquired the data, which L. Zhang, L. Lu, B. Li, Xiaoxiao Hu, H. Li, S. Tang, Y. Gao, J. Sweeney and X. Huang analyzed. L. Zhang, Xinyu Hu, J. Sweeney, Q. Gong and X. Huang wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.190114

Correspondence to: X. Huang, Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, China; julianahuang@163.com