Anterior default mode network and posterior insular connectivity is predictive of depressive symptom reduction following serial ketamine infusion.
Benjamin Wade, Joana R Loureiro, Ashish K Sahib, Antoni Kubicki, Shantanu Joshi, Gerhard Hellemann, Randall Espinoza, Roger P Woods, Eliza Congdon, Katherine L Narr
Psychological Medicine September 1, 2022 DOI: 10.1017/s0033291722001313 (opens in new tab)
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Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Longitudinal Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Patients with depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Four infusions over 2 weeks, assessed 24 h after last infusion |
| Topics | Default mode network Depression Esketamine Ketamine |
| Keywords | Functional connectivity Machine learning Serial ketamine infusion |
| Citations | 18 |
| Key findings | Pretreatment connectivity of the anterior default mode network and posterior insula predicted reductions in core depressive symptoms after serial ketamine infusion. |
Abstract
Ketamine is a rapidly-acting antidepressant treatment with robust response rates. Previous studies have reported that serial ketamine therapy modulates resting state functional connectivity in several large-scale networks, though it remains unknown whether variations in brain structure, function, and connectivity impact subsequent treatment success. We used a data-driven approach to determine whether pretreatment multimodal neuroimaging measures predict changes along symptom dimensions of depression following serial ketamine infusion. Patients with depression (n = 60) received structural, resting state functional, and diffusion MRI scans before treatment. Depressive symptoms were assessed using the 17-item Hamilton Depression Rating Scale (HDRS-17), the Inventory of Depressive Symptomatology (IDS-C), and the Rumination Response Scale (RRS) before and 24 h after patients received four (0.5 mg/kg) infusions of racemic ketamine over 2 weeks. Nineteen unaffected controls were assessed at similar timepoints. Random forest regression models predicted symptom changes using pretreatment multimodal neuroimaging and demographic measures. Two HDRS-17 subscales, the HDRS-6 and core mood and anhedonia (CMA) symptoms, and the RRS: reflection (RRSR) scale were predicted significantly with 19, 27, and 1% variance explained, respectively. Increased right medial prefrontal cortex/anterior cingulate and posterior insula (PoI) and lower kurtosis of the superior longitudinal fasciculus predicted reduced HDRS-6 and CMA symptoms following treatment. RRSR change was predicted by global connectivity of the left posterior cingulate, left insula, and right superior parietal lobule. Our findings support that connectivity of the anterior default mode network and PoI may serve as potential biomarkers of antidepressant outcomes for core depressive symptoms.
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 |
Citations in the library
Cited by 8
- Low-dose ketamine improved brain network integrity among patients with treatment-resistant depression and suicidal ideation. Psychiatry Research March 1, 2025
- Prophylactic (R,S)-Ketamine and (2S,6S)-Hydroxynorketamine Decrease Fear Expression by Differentially Modulating Fear Neural Ensembles. Biological Psychiatry May 1, 2025
- Natural language analysis of the structure of altered states of consciousness Journal of Psychedelic Studies May 17, 2025
- Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges Frontiers in Psychiatry October 1, 2026
- Predictors of responsiveness to ketamine: An updated systematic review of neuroimaging findings. Journal of Affective Disorders July 15, 2026
and 3 more in the library
Cites 15
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression American Journal of Psychiatry April 8, 2016
- Resting-state Network-specific Breakdown of Functional Connectivity during Ketamine Alteration of Consciousness in Volunteers Anesthesiology August 9, 2016
- Ketamine-Induced Modulation of the Thalamo-Cortical Network in Healthy Volunteers As a Model for Schizophrenia The International Journal of Neuropsychopharmacology April 19, 2015
and 10 more in the library