NCDEU Poster Session 2011

Ketamine Effect on Neuronal Remodeling in Treatment Resistant Depression as Assessed by Magnetic Resonance Imaging

Chadi G. Abdallah, MD
From the SUNY Downstate Medical Center, Brooklyn, New York.

This presentation did not receive funding.

Context: Ketamine has been shown to rapidly increase spines’ number and synaptic proteins in the medial prefrontal cortex (mPFC) of rats. However, it is unknown if ketamine exerts similar neuronal remodeling effect in humans. Alternatively, a recent study provided a proof-of-concept of detecting rapid within hours brain volumetric changes—putatively reflecting dendritic remodeling—using high resolution magnetic resonance imaging (MRI).

Aim: To determine the acute effects of intravenous ketamine administration on neuronal remodeling in patients diagnosed with treatment resistant depression (TRD).

Methods: Twelve medication free participants aged 18–65 with TRD will receive a baseline MRI followed by an open-label administration of 0.5mg per kg intravenous ketamine hydrochloride infused over 40 minutes. Multiple rating scales will be conducted at baseline (pre-infusion), at 40, 80, 120 and 240 minutes after the start of ketamine infusion. MRI acquisition and rating scales will be repeated in 24 hours.

Expected Results: We hypothesize that the administration of a single subanesthetic dose of intravenous ketamine in patients with TRD would (1) replicate previous reports of fast-acting antidepressant effects and (2) induce rapid neuronal remodeling in the responders group as evidenced by morphometric changes of the hippocampus and mPFC 24 hours after ketamine infusion.

Conclusion: These findings will propose a potential mechanism for the fast-acting antidepressant effect of ketamine and provide further understanding of the neurobiological mechanisms underlying depression.

References
Li N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959–964.

Tost H, Braus DF, Hakimi S, et al. Acute D2 receptor blockade induces rapid, reversible remodeling in human cortical-striatal circuits. Nat Neurosci. 2010;13(8):920–922.

Gorman JM, Docherty JP. A hypothesized role for dendritic remodeling in the etiology of mood and anxiety disorders. J Neuropsychiatry Clin Neurosci. 2010;22(3):256–264.

Sanacora G, Zarate CA, Krystal JH, et al. Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov. 2008;7(5):426–437.

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