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


CONCLUSIONS
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.
Laboratory of Neuroscience, LIM-27, Department and Institute of Psychiatry, University of Sao Paulo, Brazil.
Rafael T
RT
de Sousa
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.
Marcus V
MV
Zanetti
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.
Geraldo F
GF
Busatto
Department of Medicine, Nephrology Division, UNIFESP/Escola Paulista de Medicina, Sao Paulo, Brazil.
Margaret G
MG
Mouro
Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
Carlos A
CA
Zarate
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.
Wagner F
WF
Gattaz
Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
Elisa M
EM
Higa
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.
Rodrigo
R
Machado-Vieira
D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D049449:Luminescence; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D011569:Psychiatric Status Rating Scales
D000928:Antidepressive Agents; D016651:Lithium Carbonate; D009569:Nitric Oxide
Bipolar disorder; Depression; Lithium; Nitric oxide; Plasticity; Treatment