Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder

B. Kadriu, P. W. Gold, D. A. Luckenbaugh, M. S. Lener, E. D. Ballard, M. J. Niciu, I. D. Henter, L. T. Park, R. T. De Sousa, P. Yuan, Rodrigo Machado Vieira, C. A. Zarate

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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 min, 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.

LanguageEnglish
Pages1626-1631
Number of pages6
JournalMolecular Psychiatry
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2018

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Osteoprotegerin
Major Depressive Disorder
Ketamine
Osteopontin
Bone and Bones
Bone Density
Treatment-Resistant Depressive Disorder
Osteitis
Bone Cements
Bone Matrix
Bone Fractures
Osteoclasts
Bone Resorption
Osteogenesis
Antidepressive Agents
Inpatients

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Kadriu, B., Gold, P. W., Luckenbaugh, D. A., Lener, M. S., Ballard, E. D., Niciu, M. J., ... Zarate, C. A. (2018). Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder. Molecular Psychiatry, 23(7), 1626-1631. https://doi.org/10.1038/mp.2017.109

Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder. / Kadriu, B.; Gold, P. W.; Luckenbaugh, D. A.; Lener, M. S.; Ballard, E. D.; Niciu, M. J.; Henter, I. D.; Park, L. T.; De Sousa, R. T.; Yuan, P.; Machado Vieira, Rodrigo; Zarate, C. A.

In: Molecular Psychiatry, Vol. 23, No. 7, 01.07.2018, p. 1626-1631.

Research output: Contribution to journalArticle

Kadriu, B, Gold, PW, Luckenbaugh, DA, Lener, MS, Ballard, ED, Niciu, MJ, Henter, ID, Park, LT, De Sousa, RT, Yuan, P, Machado Vieira, R & Zarate, CA 2018, 'Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder' Molecular Psychiatry, vol. 23, no. 7, pp. 1626-1631. https://doi.org/10.1038/mp.2017.109
Kadriu B, Gold PW, Luckenbaugh DA, Lener MS, Ballard ED, Niciu MJ et al. Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder. Molecular Psychiatry. 2018 Jul 1;23(7):1626-1631. https://doi.org/10.1038/mp.2017.109
Kadriu, B. ; Gold, P. W. ; Luckenbaugh, D. A. ; Lener, M. S. ; Ballard, E. D. ; Niciu, M. J. ; Henter, I. D. ; Park, L. T. ; De Sousa, R. T. ; Yuan, P. ; Machado Vieira, Rodrigo ; Zarate, C. A. / Acute ketamine administration corrects abnormal inflammatory bone markers in major depressive disorder. In: Molecular Psychiatry. 2018 ; Vol. 23, No. 7. pp. 1626-1631.
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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 min, 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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