title: Oxidative stress in early stage Bipolar Disorder and the association with response to lithium.
abstract: BACKGROUND
  Several studies have described increased oxidative stress (OxS) parameters and imbalance of antioxidant enzymes in Bipolar Disorder (BD) but few is know about the impact of treatment at these targets. However, no study has evaluated OxS parameters in unmedicated early stage BD and their association with lithium treatment in bipolar depression.
  
  
  METHODS
  Patients with BD I or II (n = 29) in a depressive episode were treated for 6 weeks with lithium. Plasma samples were collected at baseline and endpoint, and were also compared to age-matched controls (n = 28). The thiobarbituric acid reactive substances (TBARS), and the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities were measured.
  
  
  RESULTS
  Subjects with BD depression at baseline presented a significant increase in CAT (p = 0.005) and GPx (p < 0.001) levels, with lower SOD/CAT ratio (p = 0.001) and no changes on SOD or TBARS compared to healthy controls. Regarding therapeutics, lithium only induced a decrease in TBARS (p = 0.023) and SOD (p = 0.029) levels, especially in BDII. Finally, TBARS levels were significantly lower at endpoint in lithium responders compared to non-responders (p = 0.018) with no difference in any biomarker regarding remission.
  
  
  CONCLUSIONS
  The present findings suggest a reactive increase in antioxidant enzymes levels during depressive episodes in early stage BD with minimal prior treatment. Also, decreased lipid peroxidation (TBARS) levels were observed, associated with lithium's clinical efficacy. Overall, these results reinforce the role for altered oxidative stress in the pathophysiology of BD and the presence of antioxidant effects of lithium in the prevention of illness progression and clinical efficacy.
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors: Rafael T
authors: RT
authors: de Sousa
authors: Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors: Carlos A
authors: CA
authors: Zarate
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil.
authors: Marcus V
authors: MV
authors: Zanetti
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors: Alana C
authors: AC
authors: Costa
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil.
authors: Leda L
authors: LL
authors: Talib
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil.
authors: Wagner F
authors: WF
authors: Gattaz
authors: Laboratory of Neuroscience, LIM-27, Institute and Department of Psychiatry, University of Sao Paulo, Brazil; Experimental Therapeutics and Pathophysiology Branch (ETPB), National Institute of Mental Health, NIH, Bethesda, MD, USA; Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Brazil. Electronic address: machadovieirar@gmail.com.
authors: Rodrigo
authors: R
authors: Machado-Vieira
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism*; D002374:Catalase / Q000097:blood; D003863:Depression; D005260:Female; D005979:Glutathione Peroxidase / Q000097:blood; D006801:Humans; D016651:Lithium Carbonate / Q000627:therapeutic use*; D008297:Male; D018384:Oxidative Stress; D013482:Superoxide Dismutase / Q000097:blood; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D017392:Thiobarbituric Acid Reactive Substances; D016651:Lithium Carbonate; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
keywords: Bipolar Disorder; Depression; Lithium; Neuroprotection; Oxidative stress