Abstract
Background: Ketamine is a highly effective antidepressant for patients with treatment-resistant major depressive disorder (MDD). Resting-state functional magnetic resonance imaging studies show disruptions of functional connectivity (FC) between limbic regions and resting-state networks (RSNs) in MDD, including the default mode network, central executive network (CEN), and salience network (SN). Here, we investigated whether serial ketamine treatments change FC between limbic structures and RSNs. Methods: Patients with MDD (n = 44) were scanned at baseline (time 1 [T1]) and 24 hours after the first (T2) and fourth (T3) infusions of ketamine. Healthy control subjects (n = 50) were scanned at baseline, with a subgroup (n = 17) being rescanned at 2 weeks. Limbic regions included the amygdala and hippocampus, and RSNs included the default mode network, CEN, and SN. Results: Ketamine increased right amygdala FC to the right CEN (p = .05), decreased amygdala FC to the left CEN (p = .005) at T2 versus T1 (p = .015), which then increased at T3 versus T2 (p = .002), and decreased left amygdala FC to the SN (p = .016). Decreased left amygdala to SN FC at T2 predicted improvements in anxiety at T3 (p = .006). Ketamine increased right hippocampus FC to the left CEN (p = .001), and this change at T2 predicted decreased anhedonia at T3 (p = .005). Conclusions: Ketamine modulates FC between limbic regions and RSNs implicated in MDD. Increases in FC between limbic regions and the CEN suggest that ketamine may be involved in restoring top-down control of emotion processing. FC decreases between the left amygdala and SN suggest that ketamine may ameliorate MDD-related dysconnectivity in these circuits. Early FC changes between limbic regions and RSNs may be predictive of clinical improvements.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 735-744 |
| Number of pages | 10 |
| Journal | Biological Psychiatry: Cognitive Neuroscience and Neuroimaging |
| Volume | 6 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2021 |
Funding
This study was supported by National Institute of Mental Health Grant No. F32MH111193 (to MMV), Grant No. K24MH102743 (to KLN), and Grant No. U01MH110008 (to KLN and RTE) and the Muriel Harris Chair in Geriatric Psychiatry (to RTE). This research was also supported by the University of California, Los Angeles (UCLA) Depression Grand Challenge, support for which is provided by the UCLA Office of the Chancellor and philanthropy. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. The authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Biomarkers of Fast Acting Therapies in Major Depression; https://clinicaltrials.gov/ct2/show/NCT02165449; NCT02165449. This study was supported by National Institute of Mental Health Grant No. F32MH111193 (to MMV), Grant No. K24MH102743 (to KLN), and Grant No. U01MH110008 (to KLN and RTE) and the Muriel Harris Chair in Geriatric Psychiatry (to RTE). This research was also supported by the University of California , Los Angeles (UCLA) Depression Grand Challenge, support for which is provided by the UCLA Office of the Chancellor and philanthropy. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health.
Keywords
- Antidepressant treatment
- Functional connectivity
- Ketamine
- Major depression
- Mood disorders
- Personalized medicine
ASJC Scopus subject areas
- Radiology Nuclear Medicine and imaging
- Clinical Neurology
- Cognitive Neuroscience
- Biological Psychiatry