. 2014 Aug:55:96-100.

doi: 10.1016/j.jpsychires.2014.03.023. Epub 2014 Apr 12.

Lithium increases nitric oxide levels in subjects with bipolar disorder during depressive episodes

Rafael T de Sousa¹, Marcus V Zanetti², Geraldo F Busatto³, Margaret G Mouro⁴, Carlos A Zarate Jr⁵, Wagner F Gattaz⁶, Elisa M Higa⁵, Rodrigo Machado-Vieira⁷

Affiliations

¹ Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
² Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
³ Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
⁴ Department of Medicine, Nephrology Division, UNIFESP/Escola Paulista de Medicina, Sao Paulo, Brazil.
⁵ Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
⁶ Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil.
⁷ Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA. Electronic address: machadovieirar@gmail.com.

PMID: 24768108
PMCID: PMC4084566
DOI: 10.1016/j.jpsychires.2014.03.023

Lithium increases nitric oxide levels in subjects with bipolar disorder during depressive episodes

Rafael T de Sousa et al. J Psychiatr Res. 2014 Aug.

. 2014 Aug:55:96-100.

doi: 10.1016/j.jpsychires.2014.03.023. Epub 2014 Apr 12.

Authors

Rafael T de Sousa¹, Marcus V Zanetti², Geraldo F Busatto³, Margaret G Mouro⁴, Carlos A Zarate Jr⁵, Wagner F Gattaz⁶, Elisa M Higa⁵, Rodrigo Machado-Vieira⁷

Affiliations

¹ Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
² Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
³ Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Laboratory of Psychiatric Neuroimaging, LIM-21, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
⁴ Department of Medicine, Nephrology Division, UNIFESP/Escola Paulista de Medicina, Sao Paulo, Brazil.
⁵ Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
⁶ Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil.
⁷ Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil; Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA. Electronic address: machadovieirar@gmail.com.

PMID: 24768108
PMCID: PMC4084566
DOI: 10.1016/j.jpsychires.2014.03.023

Abstract

Background: Altered nitric oxide (NO) signaling has been associated with the pathophysiology of Bipolar Disorder (BD), directly affecting neurotransmitter release and synaptic plasticity cascades. Lithium has shown to regulate NO levels in preclinical models. However, no study has addressed peripheral NO levels in unmedicated BD. Also, lithium's effects on NO levels have not been studied in humans.

Methods: Plasma NO was evaluated in subjects with BD I and II during a depressive episode (n = 26). Subjects had a score of ≥18 in the 21-item Hamilton Depression Rating Scale and were followed-up during a 6-week trial with lithium. Plasma NO levels were also compared to matched healthy controls (n = 28). NO was determined by chemiluminescence method.

Results: Lithium treatment significantly increased plasma NO levels after 6 weeks of treatment in comparison to baseline levels in bipolar depression (p = 0.016). Baseline NO levels during depressive episodes showed no difference when matching up to healthy controls (p = 0.66).

Conclusion: The present findings suggest that lithium upregulates NO signaling in unmedicated BD with short illness duration. Further studies with larger samples are needed to confirm the effects of lithium on NO pathway and its association with synaptic plasticity and therapeutics of BD.

Keywords: Bipolar disorder; Depression; Lithium; Nitric oxide; Plasticity; Treatment.

Published by Elsevier Ltd.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: CAZ is listed as co-inventor on a patent for the use of ketamine in major depression and has assigned their patent rights on ketamine to the US government. The other authors report no conflict of interest.

Figures

**Fig. 1**
Comparison of nitric oxide levels in bipolar depression patients before treatment, after treatment, and in healthy controls. Bars display standard error mean. *p = 0.016.

See this image and copyright information in PMC

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Lithium increases nitric oxide levels in subjects with bipolar disorder during depressive episodes

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Lithium increases nitric oxide levels in subjects with bipolar disorder during depressive episodes

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