San Francisco Veterans Affairs Medical Center, San Francisco, California; University of California, San Francisco, San Francisco, California. Electronic address: daniel.mathalon@ucsf.edu.
2 papers in the library · 7 citations · publishing 2020-2025
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.
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.