Ketamine treatment improves cognitive function in people with treatment-resistant depression, and these improvements last at least five weeks. In a study of 66 patients receiving four ketamine infusions, significant gains occurred in inhibition, working memory, processing speed, and overall fluid cognition after the first and fourth infusions. Processing speed and overall fluid cognition remained improved at a five-week follow-up, even though depressive symptoms had largely returned to baseline by then. Baseline working memory and changes in inhibition were moderately linked to antidepressant response, but cognitive improvements were statistically independent of mood changes, suggesting ketamine acts on overlapping but distinct brain systems.
In patients with treatment-resistant depression, smaller hippocampal subfield volumes (left CA4 and GC-ML-DG) were observed before ketamine treatment compared to healthy controls. Four ketamine infusions over two weeks did not change hippocampal subfield volumes, and pre-treatment volumes did not predict improvement in depressive symptoms. However, smaller pre-treatment left CA4 and GC-ML-DG volumes were associated with greater improvement in processing speed after ketamine, and larger right CA3 volume was linked to better working memory at follow-up. Baseline hippocampal subfield volumes may serve as biomarkers for cognitive, but not antidepressant, response to ketamine.