For adults with treatment-resistant depression, adding mindfulness-based cognitive therapy (MBCT) to usual pharmacotherapy produced a significantly greater reduction in depression severity (36.6% vs. 25.3% on the Hamilton Depression Rating Scale) and a higher rate of treatment responders (30.3% vs. 15.3%) after eight weeks, compared with an active control program of physical fitness, music therapy, and nutritional education. Remission rates did not differ significantly between groups (22.4% vs. 13.9%). Higher state anxiety, perceived stress, and personality disorder were associated with worse outcomes. MBCT appears to be a viable adjunctive treatment for treatment-resistant depression.
Abnormalities in the 40-Hz auditory steady-state response (ASSR), a measure of gamma-band brain activity, appear in schizophrenia and in animal models with reduced NMDA receptor function. This study compared 40-Hz ASSR deficits in schizophrenia patients to those induced by ketamine (an NMDA receptor antagonist) in healthy participants. Schizophrenia patients showed increased prestimulus broadband gamma power and reduced evoked power, total power, and phase-locking factor, replicating prior work, but no phase delay. Ketamine similarly increased prestimulus gamma power and reduced evoked power, total power, and phase-locking factor, while also advancing the ASSR phase. Direct comparison revealed significant differences only in phase, suggesting NMDA receptor hypofunction contributes to gamma oscillation abnormalities in schizophrenia.
A robust and reproducible brain connectivity fingerprint (CFP) was identified during ketamine infusion in healthy participants, characterized by reduced connectivity within primary cortices and the executive network, but increased connectivity between the executive network and the rest of the brain. This same CFP measured one week after treatment in major depressive disorder patients predicted response to eight weeks of sertraline, but not placebo. The findings suggest a brain network biomarker that links ketamine's acute effects to the mechanisms of conventional antidepressants.
Older age is associated with slower and less durable antidepressant responses to intravenous ketamine in veterans with treatment-refractory depression. The study found that age-related declines in neuroplasticity may attenuate ketamine's mechanism of action, which involves glutamatergic signaling and synaptogenesis. Older patients took longer to achieve a clinically meaningful reduction in depression symptoms and were more likely to relapse sooner after the infusion series ended. The findings suggest that age is a key patient characteristic influencing the speed and durability of ketamine's antidepressant effects.