title: A Selective Association between Central and Peripheral Lithium Levels in Remitters in Bipolar Depression: A 3T-(7) Li Magnetic Resonance Spectroscopy Study.
abstract: OBJECTIVE
  The objective of this study was to evaluate brain lithium levels using (7) Li magnetic resonance spectroscopy after 6 weeks of lithium therapy in bipolar depression to test the hypothesis that brain and plasma lithium are correlated. It was also tested whether responders and remitters have different pharmacokinetics, blood and brain lithium levels (ratio) compared with those presenting suboptimal antidepressant improvement.
  
  
  METHODS
  Twenty-three patients with bipolar disorder (I and II) during depressive episodes were included and followed up for 6 weeks at the University of Sao Paulo using flexible dose of lithium (450-900 mg/day). Sixteen patients were drug-naïve. At endpoint, patients underwent a (7) Li-MRS scan and brain lithium concentrations were calculated.
  
  
  RESULTS
  A significant association between central and peripheral lithium levels was found only in remitters (r = 0.7, P = 0.004) but not in non-remitters (r = -0.12, P = 0.76). Also, brain lithium (but not plasma) was inversely correlated with age (r = -0.46, P = 0.025). Plasma lithium did not correlate with any clinical outcome, lithium dosage or adverse effects.
  
  
  CONCLUSIONS
  These findings suggest that non-remitters may not transport lithium properly to the brain, which may underlie treatment resistance to lithium in BD. Future studies with (7) Li-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted.
authors.affiliation: Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.|Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH, Bethesda, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.|Laboratory of Magnetic Resonance in Neuroradiology, LIM- 44, Institute and Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Otaduy
authors.affiliation: Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: M V
authors.initials: MV
authors.lastname: Zanetti
authors.affiliation: Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: R T
authors.initials: RT
authors.lastname: De Sousa
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: V V
authors.initials: VV
authors.lastname: Dias
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.|Laboratory of Magnetic Resonance in Neuroradiology, LIM- 44, Institute and Department of Radiology, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: C C
authors.initials: CC
authors.lastname: Leite
authors.affiliation: Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: O V
authors.initials: OV
authors.lastname: Forlenza
authors.affiliation: Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.|Laboratory of Psychiatric Neuroimaging, LIM-21, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: G F
authors.initials: GF
authors.lastname: Busatto
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Texas Medical School, Houston, TX, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Soares
authors.affiliation: Laboratory of Neuroscience, LIM- 27, Institute and Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil.|Center for Interdisciplinary Research on Applied Neurosciences (NAPNA), University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: W F
authors.initials: WF
authors.lastname: Gattaz
mesh_terms: D000328:Adult; D018692:Antimanic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male
chemical_list: D018692:Antimanic Agents; D018020:Lithium Compounds
keywords: bipolar disorder; depression; imaging; lithium; magnetic resonance spectroscopy; spectroscopy; treatment