Structural Connectivity Associated with Clinical Response Following Ketamine Treatment in Patients with Treatment-Resistant Depression

Ketamine is a therapeutic option for treatment-resistant depression (TRD) due to its rapid antidepressant effects. We aimed to identify corticolimbic structural connectivity (nSC) patterns before and after ketamine treatment and their association with clinical response. Sixteen patients with TRD underwent diffusion-weighted MRI before and after treatment. nSC was estimated by probabilistic tractography between eight bilateral regions. Clinical response was assessed by percentage change in the Hamilton Depression Rating Scale and correlated with nSC using Spearman correlations. At baseline, connectivity between the left posterior cingulate cortex (PCC) and right ventrolateral prefrontal cortex (vlPFC) was positively associated with response. Post-treatment nSC revealed four connections positively and five negatively associated with response. The positive subnetwork comprised the right orbitofrontal cortex with both thalami and the interhemispheric PCC connection. The negative subnetwork included connections involving both vlPFCs, the left vlPFC with the right dorsolateral prefrontal cortex (dlPFC), the right dlPFC with the left PCC, and the right anterior insula with the left amygdala and left subgenual cingulate cortex. Overall, post-treatment nSC showed more extensive associations with response than baseline nSC, revealing differential corticolimbic circuits consistent with Menon’s Tripartite Model.