Synaptic density (SV2A) tracks illness chronicity rather than symptom severity in major depressive disorder

Synaptic loss has been proposed as a key mechanism in major depressive disorder (MDD). Positron emission tomography with [11C]UCB-J enables in vivo quantification of synaptic vesicle glycoprotein 2A (SV2A), a proxy marker of synaptic density. A landmark study by Holmes et al reported an inverse association between depression severity and SV2A binding in frontolimbic regions. As a replication, we examined this association in [11C]UCB-J PET data from 34 unmedicated individuals with MDD, focusing on the dorsolateral prefrontal cortex, anterior cingulate cortex, and hippocampus. We found no suppor

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