A single intravenous infusion of ketamine (0.5 mg/kg) in 98 adults with unipolar depression who had not responded to at least one antidepressant was associated with rapid changes in gray matter microstructure measured by diffusion tensor imaging (DTI) 24 hours later. Greater decreases in DTI mean diffusivity, a marker of neuroplasticity enhancement, in several brain regions (left and right BA10, left amygdala) correlated with larger improvements in depression scores, particularly in the ketamine group. In the hippocampus, the relationship was reversed for one depression scale. The findings suggest that ketamine's acute antidepressant effects may involve rapid neuroplastic changes detectable with brain imaging.
A combination of ketamine infusion and a digital training program called automated self-association training (ASAT) produced more positive implicit self-associations immediately after treatment in adults with treatment-resistant depression, compared to control groups that received only one active component. These changes in implicit self-worth tracked with concurrent depression symptom improvement across all groups and specifically predicted longer-term depression relief at 30 days for the combined treatment group. The findings indicate that shifting implicit self-esteem during a post-ketamine 'plasticity window' is a key mechanism behind the combined treatment's antidepressant effect, confirming the intended cognitive target.