Functional connectivity between the amygdala and subgenual cingulate gyrus predicts the antidepressant effects of ketamine in patients with treatment‐resistant depression
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Aim: Approximately one‐third of patients with major depressive disorder develop treatment‐resistant depression. One‐third of patients with treatment‐resistant depression demonstrate resistance to ketamine, which is a novel antidepressant effective for this disorder. The objective of this study was to examine the utility of resting‐state functional magnetic resonance imaging for the prediction of treatment response to ketamine in treatment‐resistant depression. Methods: An exploratory seed‐based resting‐state functional magnetic resonance imaging analysis was performed to examine baseline resting‐state functional connectivity differences between ketamine responders and nonresponders before treatment with multiple intravenous ketamine infusions. Results: Fifteen patients with treatment‐resistant depression received multiple intravenous subanesthetic (0.5 mg/kg/40 minutes) ketamine infusions, and nine were identified as responders. The exploratory resting‐state functional magnetic resonance imaging analysis identified a cluster of significant baseline resting‐state functional connectivity differences associating ketamine response between the amygdala and subgenual anterior cingulate gyrus in the right hemisphere. Using anatomical region of interest analysis of the resting‐state functional connectivity, ketamine response was predicted with 88.9% sensitivity and 100% specificity. The resting‐state functional connectivity of significant group differences between responders and nonresponders retained throughout the treatment were considered a trait‐like feature of heterogeneity in treatment‐resistant depression. Conclusion: This study suggests the possible clinical utility of resting‐state functional magnetic resonance imaging for predicting the antidepressant effects of ketamine in treatment‐resistant depression patients and implicated resting‐state functional connectivity alterations to determine the trait‐like pathophysiology underlying treatment response heterogeneity in treatment‐resistant depression.
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Increased pretreatment FC between the sgACC and amygdala predicted nonresponse to ketamine.
“Critically, increased pretreatment FC between the sgACC and amygdala predicted nonresponse to ketamine [200] and reduced dACC-pgACC FC correlated with a reduction in suicidal ideation [199].”
From Prefrontal cortex and depression (2022) · cites this paper as [200]
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- Authors
- Nakamura, T., Tomita, M., Horikawa, N., Ishibashi, M., Uematsu, K., Hiraki, T., Abe, T., & Uchimura, N.
- Affiliations
- Kurume University (JP)
- Corresponding author
- Nakamura, Tomoyuki
- Venue
- Neuropsychopharmacology Reports
- Publisher
- Wiley
- Published
- 2021-02-21
- Volume
- 41
- Issue
- 2
- Pages
- 168-178
- ISSN
- 2574-173X (ISSN-L)
- PMC
- PMC8340826
- OpenAlex
- W3129697370
- Cited by
- 28
- References
- 68
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 2
- FWCI
- 2.92
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Neuropsychopharmacology Reports (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (acceptedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Keywords
- treatment-resistant depression, ketamine, antidepressant response prediction, resting-state functional connectivity, amygdala, treatment response heterogeneity, major depressive disorder, neuroimaging biomarkers
- MeSH terms
- Amygdala, Antidepressive Agents, Depression, Depressive Disorder, Major, Major Depressive Disorder, Gyrus Cinguli, Humans, Ketamine
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