Functional connectivity of the amygdala and the antidepressant and antisuicidal effects of repeated ketamine infusions in major depressive disorder

Haiyan Liu; Chengyu Wang; Xiaofeng Lan; Weicheng Li; Fan Zhang; Ling Fu; Yanxiang Ye; Yuping Ning; Yanling Zhou

doi:10.3389/fnins.2023.1123797

Functional connectivity of the amygdala and the antidepressant and antisuicidal effects of repeated ketamine infusions in major depressive disorder

Front Neurosci. 2023 Feb 2:17:1123797. doi: 10.3389/fnins.2023.1123797. eCollection 2023.

Authors

Haiyan Liu^{1

2

3}, Chengyu Wang^{1

2

3}, Xiaofeng Lan^{1

2

3}, Weicheng Li^{1

2

3

4}, Fan Zhang^{1

2

3

4}, Ling Fu^{1

2

3

4}, Yanxiang Ye^{1

2

3}, Yuping Ning^{1

2

3

4}, Yanling Zhou^{1

2

3}

Affiliations

¹ Department of Child and Adolescent Psychiatry, Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
² Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
³ Guangdong Engineering Technology Research Center for Translational Medicine of Mental Disorders, Guangzhou, China.
⁴ Department of Psychology, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.

Abstract

Background: Dysfunction of the amygdala is the core pathogenesis of major depressive disorder (MDD). However, it remains unclear whether ketamine treatment could modulate characteristics of amygdala-related networks. We aimed to explore the relationship between changes in the resting-state functional connectivity (RSFC) of the amygdala and the treatment of ketamine in MDD patients and to identify important neuroimaging predictors of treatment outcome.

Methods: Thirty-nine MDD patients received six subanesthetic dose infusions of ketamine. Depressive and suicidal symptoms were assessed and magnetic resonance imaging (MRI) scans were performed before and after six ketamine infusions. Forty-five healthy controls also underwent once MRI scans. Seed-based RSFC analyses were performed, focusing on the bilateral amygdala.

Results: After ketamine treatment, the RSFC between the left amygdala (LA) and the left medial superior frontal gyrus (mSFG) of MDD patients enhanced significantly, and this change was positively correlated with the reduction in depressive symptoms (r = 0.40, p = 0.012). The combination baseline RSFC of LA - right putamen and right amygdala (RA) - right putamen was related to the antidepressant and antisuicidal effects of ketamine. The combination baseline RSFC of LA - right putamen and RA - right putamen could predict the ineffective antidepressant (AUC = 0.739, p = 0.011) and antisuicidal effects of ketamine (AUC = 0.827, p = 0.001).

Conclusion: Ketamine can regulate the relevant circuits of amygdala and mSFG, and the baseline RSFC between bilateral amygdala and right putamen may be a predictor of the response of ketamine's antidepressant and antisuicidal treatment.

Clinical trial registration: https://www.chictr.org.cn/showproj.aspx?proj=20875, identifier ChiCTR-OOC-17012239.

Keywords: amygdala; antidepressant; functional connectivity; ketamine; major depressive disorder.

Grants and funding

This work was supported by the National Natural Science Foundation of China (grant number 81801343), the Guangdong Basic and Applied Basic Research Foundation (grant number 2019A1515011366), Science and Technology Plan Project of Guangdong Province (No. 2019B030316001), Guangzhou Municipal Key Discipline in Medicine (2017-2019), and Science and Technology Plan Project of Guangzhou (202102020557). The funding source had no role in the study design, analysis or interpretation of data or in the preparation of the report or decision to publish.