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Introduction Ketamine, an NMDAR antagonist, produces fast antidepressant response with a maximum efficacy 24h after infusion [1]. Animal studies showed that ketamine generates higher synaptic plasticity via induction of Brain-derived neurotrophic factor (BDNF) [2]. Patients with depression have lower blood level of BDNF and show an increase after ketamine infusion [4]. Besides, depressed patients have hyperconnectivity within the Default mode network (DMN) [5]. Ketamine decreases the Functional Connectivity (FC) in healthy subjects between posterior cingulate cortex (PCC) and medial prefrontal cortex (mPFC), two main regions within DMN [6], revealing possible mechanisms of the antidepressant effect. Methods In a double-blind study, 81 healthy subjects received infusion of either ketamine (0.5 mg/kg) or saline. In each subject, resting state fMR images (TR= 2.8s, voxel size= 2 × 2 × 2 mm3, 7T ) and plasma blood samples were acquired at baseline and 24h post-infusion. Ketamine (n=32) and placebo (n=30) groups were preprocessed using scripts developed in the functional connectome 1000 project. Dorsal PCC (dPCC) was chosen as a priori seed region [6] and FC maps were calculated. The mean FC value was extracted from clusters showing significant change after infusion. Extracted FC values were correlated with the plasma BDNF at 24h (n=45). Results 24h after infusion, ketamine treated subjects showed higher BDNF level compared to placebo (p=0.015). A decrease in FC between the dPCC and both dorsolateral PFC (p=0.005 FWE) and two cluster in mPFC (p=0.001 p=0.030 FWE) was observed 24h after infusion. Subjects with higher BDNF level after ketamine show significantly higher FC disconnection between dorsal PCC and mPFC (r= 0.64, p=0.006). Conclusions Ketamine decreases FC within the DMN and increases BDNF 24h after ketamine. Higher BDNF level correlates with stronger FC disconnection between anterior (mPFC) and posterior (dPCC) part of DMN. This finding highlights the role of BDNF as a potential biomarker for network remodeling in the brain. 1 Zarate et al. (2006) A Randomized Trial of an N-methyl-D- aspartate Antagonist in Treatment-Resistant Major Depression. 2 Duman et al. (2012) Signaling pathways underlying the rapid antidepressant actions of ketamine. 3 Haile (2013) Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. 4 Kaiser et al. (2015). Large-scale network dysfunction in major depressive disorder. 5 Scheidegger et al. (2012). Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action.
