Modulation of habenular and nucleus accumbens functional connectivity by ketamine in major depression.
Brandon Taraku, Joana R Loureiro, Ashish K Sahib, Artemis Zavaliangos-Petropulu, Noor B. Al-Sharif, Amber M Leaver, Benjamin Wade, Shantanu Joshi, Roger P Woods, Randall Espinoza, Katherine L Narr
Brain and Behavior June 1, 2024 DOI: 10.1002/brb3.3511 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 58 |
| Population | Adults with major depressive disorder |
| Intervention | Ketamine infusion |
| Dose | 0.5 mg/kg |
| Duration | Four infusions over 2-3 weeks, with scans and assessments at baseline and 24 hours after the last infusion |
| Topics | Ketamine Depression Esketamine |
| Keywords | FMRI Habenula Nucleus accumbens Depression treatment Brain imaging Psychopharmacology Reward circuits |
| Citations | 11 |
| Key findings | Subanesthetic ketamine modulates functional connectivity between the habenula and nucleus accumbens with visual, parietal, and cerebellar regions, and these changes correlate with improvements in mood and anhedonia in major depressive disorder. |
Abstract
Major depressive disorder (MDD) is associated with dysfunctional reward processing, which involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Since ketamine elicits rapid antidepressant and antianhedonic effects in MDD, this study sought to investigate how serial ketamine infusion (SKI) treatment modulates static and dynamic functional connectivity (FC) in Hb and NAc functional networks. MDD participants (n = 58, mean age = 40.7 years, female = 28) received four ketamine infusions (0.5 mg/kg) 2-3 times weekly. Resting-state functional magnetic resonance imaging (fMRI) scans and clinical assessments were collected at baseline and 24 h post-SKI. Static FC (sFC) and dynamic FC variability (dFCv) were calculated from left and right Hb and NAc seeds to all other brain regions. Changes in FC pre-to-post SKI, and correlations with changes with mood and anhedonia were examined. Comparisons of FC between patients and healthy controls (HC) at baseline (n = 55, mean age = 32.6, female = 31), and between HC assessed twice (n = 16) were conducted as follow-up analyses. Following SKI, significant increases in left Hb-bilateral visual cortex FC, decreases in left Hb-left inferior parietal cortex FC, and decreases in left NAc-right cerebellum FC occurred. Decreased dFCv between left Hb and right precuneus and visual cortex, and decreased dFCv between right NAc and right visual cortex both significantly correlated with improvements in mood ratings. Decreased FC between left Hb and bilateral visual/parietal cortices as well as increased FC between left NAc and right visual/parietal cortices both significantly correlated with improvements in anhedonia. No differences were observed between HC at baseline or over time. Subanesthetic ketamine modulates functional pathways linking the Hb and NAc with visual, parietal, and cerebellar regions in MDD. Overlapping effects between Hb and NAc functional systems were associated with ketamine's therapeutic response.
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 6
- The dynamics of AMPA receptors underlies the efficacy of ketamine in treatment resistant patients with depression Molecular Psychiatry March 5, 2026
- Multiband ALFF in patients with major depressive disorder treated with esketamine and sertraline: A preliminary study Brain Research Bulletin October 6, 2026
- Default mode network functional connectivity following treatment with conventional antidepressants and (es)ketamine in major depressive disorder: A systematic review Psychiatry Research Neuroimaging September 17, 2026
- Structural Neurotoxic and Neuroprotective Effects of Ketamine and Esketamine in Preclinical and Human Studies: A Systematic Review Research Square May 27, 2026
- Modulation of functional network co-activation pattern dynamics following ketamine treatment in major depression. Imaging Neuroscience 2025
and 1 more in the library
Cites 11
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression Translational Psychiatry October 14, 2014
- The effects of ketamine on dopaminergic function: meta-analysis and review of the implications for neuropsychiatric disorders Molecular Psychiatry October 3, 2017
- Ketamine and rapid-acting antidepressants: a new era in the battle against depression and suicide F1000Research May 24, 2018
and 6 more in the library