Modulation of inhibitory control networks relate to clinical response following ketamine therapy in major depression.
Ashish K Sahib, Joana Ra Loureiro, Megha M Vasavada, Antoni Kubicki, Benjamin Wade, Shantanu Joshi, Roger P Woods, Eliza Congdon, Randall Espinoza, Katherine L Narr
Translational Psychiatry July 30, 2020 DOI: 10.1038/s41398-020-00947-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 47 |
| Population | Patients with treatment-resistant depression and healthy controls |
| Intervention | Intravenous ketamine |
| Dose | 0.5 mg/kg |
| Duration | 24 h after one and four infusions |
| Topics | Depression Esketamine Ketamine |
| Citations | 37 |
| Key findings | Ketamine treatment reduced brain activation in the inhibitory control network, and lower pre-treatment activation in the supplementary motor area distinguished remitters from non-remitters and normalized with treatment. |
Abstract
Subanesthetic ketamine is found to induce fast-acting and pronounced antidepressant effects, even in treatment resistant depression (TRD). However, it remains unclear how ketamine modulates neural function at the brain systems-level to regulate emotion and behavior. Here, we examined treatment-related changes in the inhibitory control network after single and repeated ketamine therapy in TRD. Forty-seven TRD patients (mean age = 38, 19 women) and 32 healthy controls (mean age = 35, 18 women) performed a functional magnetic resonance imaging (fMRI) response inhibition task at baseline, and 37 patients completed the fMRI task and symptom scales again 24 h after receiving both one and four 0.5 mg/kg intravenous ketamine infusions. Analyses of fMRI data addressed effects of diagnosis, time, and differences between treatment remitters and non-remitters. Significant decreases in brain activation were observed in the inhibitory control network, including in prefrontal and parietal regions, and visual cortex following serial ketamine treatment, p < 0.05 corrected. Remitters were distinguished from non-remitters by having lower functional activation in the supplementary motor area (SMA) prior to treatment, which normalized towards controls following serial ketamine treatment. Results suggest that ketamine treatment leads to neurofunctional plasticity in executive control networks including the SMA during a response-inhibitory task. SMA changes relate to reductions in depressive symptoms, suggesting modulation of this network play an important role in therapeutic response. In addition, early changes in the SMA network during response inhibition appear predictive of overall treatment outcome, and may serve as a biomarker of treatment response.