Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

Bashkim Kadriu; Philip W Gold; David A Luckenbaugh; Marc S Lener; Elizabeth D Ballard; Mark J Niciu; Ioline D Henter; Lawrence T Park; Rafael Teixeira De Sousa; Peixiong Yuan; Rodrigo Machado-Vieira; Carlos A Zarate

doi:10.1038/mp.2017.109

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Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

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Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder

Bashkim Kadriu, Philip W Gold, David A Luckenbaugh, Marc S Lener, Elizabeth D Ballard, Mark J Niciu, Ioline D Henter, Lawrence T Park, Rafael Teixeira De Sousa, Peixiong Yuan, …

Molecular psychiatry, Vol.23(7), pp.1626-1631

07/2018

DOI: 10.1038/mp.2017.109

PMID: 28555075

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https://www.ncbi.nlm.nih.gov/pmc/articles/5709243View

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Abstract

Patients with major depressive disorder (MDD) have clinically relevant, significant decreases in bone mineral density (BMD). We sought to determine if predictive markers of bone inflammation—the osteoprotegerin (OPG)-RANK-RANKL system or osteopontin (OPN)—play a role in the bone abnormalities associated with MDD and, if so, whether ketamine treatment corrected the abnormalities. The OPG-RANK-RANKL system plays the principal role in determining the balance between bone resorption and bone formation. RANKL is the osteoclast differentiating factor and diminishes BMD. OPG is a decoy receptor for RANKL, thereby increasing BMD. OPN is the bone glue that acts as a scaffold between bone tissues matrix composition to bind them together and is an important component of bone strength and fracture resistance. Twenty-eight medication-free inpatients with treatment-resistant MDD and 16 healthy controls (HCs) participated in the study. Peripheral bone marker levels and their responses to IV ketamine infusion in MDD patients and HCs were measured at four time points: at baseline, and post-infusion at 230 minutes, Day 1, and Day 3. Patients with MDD had significant decreases in baseline OPG/RANKL ratio and in plasma OPN levels. Ketamine significantly increased both the OPG/RANKL ratio and plasma OPN levels and significantly decreased RANKL levels. Bone marker levels in HCs remained unaltered. We conclude that the OPG-RANK-RANKL system and the OPN system play important roles in the serious bone abnormalities associated with MDD. These data suggest that in addition to its antidepressant effects, ketamine also has a salutary effect on a major medical complication of depressive illness.

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Title: Subtitle: Acute Ketamine Administration Corrects Abnormal Inflammatory Bone Markers in Major Depressive Disorder
Creators: Bashkim Kadriu - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Philip W Gold - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
David A Luckenbaugh - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Marc S Lener - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Elizabeth D Ballard - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Mark J Niciu - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Ioline D Henter - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Lawrence T Park - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Rafael Teixeira De Sousa - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Peixiong Yuan - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Rodrigo Machado-Vieira - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Carlos A Zarate - Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA
Resource Type: Journal article
Publication Details: Molecular psychiatry, Vol.23(7), pp.1626-1631
DOI: 10.1038/mp.2017.109
PMID: 28555075
NLM abbreviation: Mol Psychiatry
ISSN: 1359-4184
eISSN: 1476-5578
Language: English
Date published: 07/2018
Academic Unit: Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984003462902771

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