Major depressive disorder is a common psychiatric condition that often responds poorly to traditional antidepressants, which can take weeks to work. Over the past two decades, the NMDA receptor antagonist ketamine has attracted attention because a single low dose produces rapid antidepressant effects in people with treatment-resistant depression. Evidence from animal and human studies suggests that ketamine triggers a surge of glutamate, initiating a cascade that promotes synaptogenesis and reverses stress-related damage, especially in the prefrontal cortex. This review covers the neurobiology of stress-related depression, the safety and efficacy of ketamine, its mechanism of action, and predictors of treatment response, along with research limitations and future directions.
A review describes the development of PET radiotracers targeting the synaptic vesicle glycoprotein 2A (SV2A), which allows measurement of synaptic density in living brains. In depression, lower SV2A density is found in people with significant depressive symptoms. A ketamine challenge was used to examine synaptogenesis in vivo. The authors stress the value of combining clinical imaging with animal model studies, presenting preliminary findings from chronic stress models. Methodological challenges and future directions for SV2A imaging, possibly alongside other neural markers, are discussed.