A Selective Association between Central and Peripheral Lithium Levels in Remitters in Bipolar Depression: A 3T-Li-7 Magnetic Resonance Spectroscopy Study

Author(s)

Machado-Vieira, R. ^{[1, 2, 3]} ; Otaduy, M. C. ^{[2, 4]} ; Zanetti, M. V. ^{[2, 3]} ; De Sousa, R. T. ^[3] ; Dias, V. V. ^[2] ; Leite, C. C. ^{[2, 4]} ; Forlenza, O. V. ^{[2, 3]} ; Busatto, G. F. ^{[2, 5]} ; Soares, J. C. ^[6] ; Gattaz, W. F. ^{[2, 3]}

Affiliation

^[1] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 - USA

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-785 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Inst & Dept Psychiat, Lab Neurosci LIM 27, Rua Dr Ovidio Pires Campos, BR-785 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst & Dept Radiol, Lab Magnet Resonance Neuroradiol LIM 44, BR-785 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Inst & Dept Psychiat, Lab Psychiat Neuroimaging LIM 21, BR-785 Sao Paulo - Brazil

^[6] Univ Texas Med Sch, Dept Psychiat & Behav Sci, Houston, TX - USA

• Document type: Journal article
• Source: ACTA PSYCHIATRICA SCANDINAVICA; v. 133, n. 3, p. 214-220, MAR 2016.
• Web of Science Citations: 8

Abstract

ObjectiveThe objective of this study was to evaluate brain lithium levels using Li-7 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. MethodTwenty-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-naive. At endpoint, patients underwent a Li-7-MRS scan and brain lithium concentrations were calculated. ResultsA 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. ConclusionThese 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 Li-7-MRS integrated with the evaluation of blood-brain barrier transport mechanisms and longitudinal clinical outcomes in BD and aging are warranted. (AU)

• FAPESP's process: 05/56464-9 - Neuroscience Imaging Center at University of São Paulo Medical School
• Grantee: Giovanni Guido Cerri
• Support Opportunities: Inter-institutional Cooperation in Support of Brain Research (CINAPCE) - Thematic Grants
• FAPESP's process: 09/14891-9 - Longitudinal study on the neuroprotective and neurotrophic effects of lithium in bipolar disorder: identification of cellular and molecular targets clinically relevant
• Grantee: Rodrigo Machado-Vieira
• Support Opportunities: Research Grants - Young Investigators Grants