Changes in white matter microstructure following serial ketamine infusions in treatment resistant depression
Brandon Taraku, Roger P Woods, Michael Boucher, Randall Espinoza, Mayank A. Jog, Noor B. Al-Sharif, Katherine L Narr, Artemis Zavaliangos-Petropulu
Human Brain Mapping January 30, 2023 DOI: 10.1002/hbm.26217 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Longitudinal Peer reviewed |
|---|---|
| Sample size | 57 |
| Population | Patients with treatment-resistant depression |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Four infusions 2–3 days apart, with scans and assessments at baseline and 24 hours after the last infusion |
| Topics | Depression Esketamine Ketamine |
| Citations | 23 |
| Key findings | Serial ketamine infusion significantly reduced depression and anhedonia scores and decreased neurite density in occipitotemporal white matter pathways, with changes in left internal capsule and superior longitudinal fasciculus neurite density correlating with anhedonia improvement. |
Abstract
Ketamine produces fast‐acting antidepressant effects in treatment resistant depression (TRD). Though prior studies report ketamine‐related changes in brain activity in TRD, understanding of ketamine's effect on white matter (WM) microstructure remains limited. We thus sought to examine WM neuroplasticity and associated clinical improvements following serial ketamine infusion (SKI) in TRD. TRD patients (N = 57, 49.12% female, mean age: 39.9) received four intravenous ketamine infusions (0.5 mg/kg) 2–3 days apart. Diffusion‐weighted scans and clinical assessments (Hamilton Depression Rating Scale [HDRS‐17]; Snaith Hamilton Pleasure Scale [SHAPS]) were collected at baseline and 24‐h after SKI. WM measures including the neurite density index (NDI) and orientation dispersion index (ODI) from the neurite orientation dispersion and density imaging (NODDI) model, and fractional anisotropy (FA) from the diffusion tensor model were compared voxelwise pre‐ to post‐SKI after using Tract‐Based Spatial Statistics workflows to align WM tracts across subjects/time. Correlations between change in WM metrics and clinical measures were subsequently assessed. Following SKI, patients showed significant improvements in HDRS‐17 (p‐value = 1.8 E‐17) and SHAPS (p‐value = 1.97 E‐10). NDI significantly decreased in occipitotemporal WM pathways (p < .05, FWER/TFCE corrected). ΔSHAPS significantly correlated with ΔNDI in the left internal capsule and left superior longitudinal fasciculus (r = −0.614, p‐value = 6.24E‐09). No significant changes in ODI or FA were observed. SKI leads to significant changes in the microstructural features of neurites within occipitotemporal tracts, and changes in neurite density within tracts connecting the basal ganglia, thalamus, and cortex relate to improvements in anhedonia. NODDI may be more sensitive for detecting ketamine‐induced WM changes than DTI.
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 11
- Rapid neuroplasticity changes and response to intravenous ketamine: a randomized controlled trial in treatment-resistant depression Translational Psychiatry May 9, 2023
- Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review. European Neuropsychopharmacology September 1, 2024
- Neural correlates of treatment response to ketamine for treatment-resistant depression: A systematic review of MRI-based studies. Psychiatry Research October 1, 2024
- Modulation of habenular and nucleus accumbens functional connectivity by ketamine in major depression. Brain and Behavior June 1, 2024
- Brain structural changes underlying clinical symptom improvement following fast-acting treatments in treatment resistant depression. Journal of Affective Disorders January 15, 2025
and 6 more in the library
Cites 15
- The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis American Journal of Psychiatry October 3, 2017
- Ketamine: 50 Years of Modulating the Mind Frontiers in Human Neuroscience November 29, 2016
- The structural–functional connectome and the default mode network of the human brain Neuroimage October 4, 2013
- Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression Translational Psychiatry October 14, 2014
- Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals Molecular Psychiatry September 14, 2020
and 10 more in the library