Ketamine-induced changes in resting state connectivity, 2 h after the drug administration in patients with remitted depression

Background: Resting state connectivity studies link ketamine's antidepressant effects with normalisation of the brain connectivity changes that are observed in depression. These changes, however, usually co-occur with improvement in depressive symptoms, making it difficult to attribute these changes to ketamine's effects per se. Aims: Our aim is to examine the effects of ketamine in brain connectivity, 2 h after its administration in a cohort of volunteers with remitted depression. Any significant changes observed in this study could provide insight of ketamine's antidepressant mechanism as they are not accompanied by symptom changes. Methods: In total, 35 participants with remitted depression (21 females, mean age = 28.5 years) participated in a double-blind, placebo-controlled study of ketamine (0.5 mg/kg) or saline. Resting state scans were acquired approximately 2 h after the ketamine infusion. Brain connectivity was examined using a seed-based approach (ventral striatum, amygdala, hippocampus, posterior cingulate cortex and subgenual anterior cingulate cortex (sgACC)) and a brain network analysis (independent component analysis). Results: Decreased connectivity between the sgACC and the amygdala was observed approximately 2 h after the ketamine infusion, compared to placebo (p(FWE) < 0.05). The executive network presented with altered connectivity with different cortical and subcortical regions. Within the network, the left hippocampus and right amygdala had decreased connectivity (p(FWE) < 0.05). Conclusions: Our findings support a model whereby ketamine would change the connectivity of brain areas and networks that are important for cognitive processing and emotional regulation. These changes could also be an indirect indicator of the plasticity changes induced by the drug.