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 H Joshi, Roger P Woods, Eliza Congdon, Randall Espinoza, Katherine L Narr
Translational psychiatry July 30, 2020 Peer reviewed DOI: 10.1038/s41398-020-00947-7 via PubMed
Summary
Subanesthetic ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD) by modulating brain function. In a study of 47 TRD patients and 32 healthy controls, significant decreases in brain activation were found in the inhibitory control network after serial ketamine treatment. Notably, remitters showed lower activation in the supplementary motor area (SMA) before treatment, which normalized after therapy. Changes in the SMA are linked to reduced depressive symptoms and may predict treatment outcomes.
Study at a glance
| Design | observational cohort |
|---|---|
| Sample size | 79 |
| Population | 47 treatment-resistant depression patients and 32 healthy controls |
| Key finding | Ketamine treatment leads to neurofunctional plasticity in executive control networks, particularly the supplementary motor area, which is associated with reductions in depressive symptoms. |
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.