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
Frontiers in Neuroscience February 2, 2023 DOI: 10.3389/fnins.2023.1123797 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 39 |
| Population | Adults with major depressive disorder; 45 healthy controls also underwent one MRI scan |
| Intervention | Ketamine |
| Dose | six subanesthetic dose infusions |
| Duration | Six ketamine infusions; MRI and symptom assessments before and after the infusions |
| Topics | Depression Esketamine Ketamine |
| Key findings | Ketamine treatment increased resting-state functional connectivity between the left amygdala and left medial superior frontal gyrus, and this change correlated with reduced depressive symptoms (r = 0.40). Baseline connectivity between the bilateral amygdala and right putamen was associated with, and predicted, antidepressant (AUC = 0.739) and antisuicidal (AUC = 0.827) response. |
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.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |