Introduction
dissociative, depressive disorder, depressed, treatment-resistant, depression, disability
Major depressive disorder is the leading cause of disability adjusted life years (DALYs) in the USA and represents an enormous public health burden [While functional neuroplasticity cannot be directly tested in the living human brain, post-mortem studies of depression show reductions in markers of neuroplasticity, including reduced BDNF and decreased synapses and synapse-related gene expression [Recent evidence has shown that ketamine, a dissociative anesthetic, has rapid and robust antidepressant effects, including in treatment-resistant patients for whom other therapies have been ineffective [To our knowledge, no one has specifically linked microstructural neuroplasticity induced by ketamine—akin to the synaptogenesis in the PFC observed in animal models—to its antidepressant effects in humans. While real-time neuroplasticity cannot be directly assessed in the intact human brain, recent advances in neuroimaging have provided evidence that structural remodeling of the human brain can be measured within hours of its occurrence. Several studies have used diffusion tensor imaging (DTI), an MRI-based framework, as an indirect marker of neuroplasticity [In the current study, we measured DTI-MD in depression-relevant brain regions (BA10, amygdala, hippocampus, and ventral ACC) before and 24-h following the administration of IV ketamine (0.5 mg/kg) or saline vehicle in depressed human subjects, and related individual differences in these acute neuroplasticity markers to the degree of clinical response 24-h post-infusion. We hypothesized that individual differences in region-specific changes in DTI-MD would predict the response to treatment primarily in patients receiving ketamine, with larger clinical improvements following ketamine tracking with greater degrees of structural change, putatively reflecting neuroplasticity enhancement.