Ketamine treatment modulates habenular and nucleus accumbens static and dynamic functional connectivity 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
medRxiv Preprint Server December 1, 2023 preprint DOI: 10.1101/2023.12.01.23299282 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort |
|---|---|
| Sample size | 58 |
| Population | Adults with major depressive disorder |
| Intervention | Ketamine |
| Dose | 0.5 mg/kg |
| Duration | Four infusions over 2-3 weeks, with assessments at baseline and 24 hours post-completion |
| Topics | Ketamine Neuroplasticity Depression Esketamine |
| Keywords | Ketamine therapy Ketamine treatment Ketamine research Depression treatment Antidepressant Mood disorder therapy Mental health treatment Psychiatric treatment Brain networks Neural circuits Brain connectivity Brain function Brain activity Anhedonia Pleasure deficit Reward processing Emotional blunting |
| Citations | 1 |
| Key findings | Subanesthetic ketamine infusions modulate static and dynamic functional connectivity in habenula and nucleus accumbens networks, with specific connectivity changes correlating with improvements in depression severity and anhedonia. |
Abstract
Dysfunctional reward processing in major depressive disorder (MDD) involves functional circuitry of the habenula (Hb) and nucleus accumbens (NAc). Ketamine elicits rapid antidepressant and alleviates anhedonia in MDD. To clarify how ketamine perturbs reward circuitry in MDD, we examined how serial ketamine infusions (SKI) modulate static and dynamic functional connectivity (FC) in Hb and NAc networks. MDD participants (n=58, mean age=40.7 years, female=28) received four ketamine infusions (0.5mg/kg) 2-3 times weekly. Resting-state fMRI scans and clinical assessments were collected at baseline and 24 hours post-SKI completion. Static FC (sFC) and dynamic FC variability (dFCv) were calculated from left and right Hb and NAc seeds to all other brain regions. Paired t-tests examined changes in FC pre-to-post SKI, and correlations were used to determine relationships between FC changes with mood and anhedonia. 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 Hamilton Depression Rating Scale. 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. Subanesthetic ketamine modulates functional pathways linking the Hb and NAc with visual, parietal, and cerebellar regions. 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 |