Bimodal Effect of Lithium Plasma Levels on Hippocampal Glutamate Concentrations in Bipolar II Depression: A Pilot Study

Autor(es)

Zanetti, Marcus V. ^{[1, 2, 3]} ; Otaduy, Maria C. ^[4] ; de Sousa, Rafael T. ^[3] ; Gattaz, Wagner F. ^{[1, 3]} ; Busatto, Geraldo F. ^{[1, 2]} ; Leite, Claudia C. ^[4] ; Machado-Vieira, Rodrigo ^{[1, 5, 3]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept & Inst Psychiat, Lab Psychiat Neuroimaging, LIM 21, BR-05508 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM 27, Mood Disorders Program, BR-05508 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Radiol, BR-05508 Sao Paulo - Brazil

^[5] NIMH, ETPB, NIH, Bethesda, MD 20892 - USA

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY; v. 18, n. 6 APR 2015.
• Citações Web of Science: 12

Resumo

Background: The hippocampus has been highly implicated in the pathophysiology of bipolar disorder (BD). Nevertheless, no study has longitudinally evaluated hippocampal metabolite levels in bipolar depression under treatment with lithium. Methods: Nineteen medication-free BD patients (78.9% treatment-naive and 73.7% with BD type II) presenting an acute depressive episode and 17 healthy controls were studied. Patients were treated for 6 weeks with lithium in an open-label trial. N-acetyl aspartate (NAA), creatine, choline, myo-Inositol, and glutamate levels were assessed in the left hippocampus before (week 0) and after (week 6) lithium treatment using 3T proton magnetic resonance spectroscopy (1H-MRS). The metabolite concentrations were estimated using internal water as reference and voxel segmentation for partial volume correction. Results: At baseline, acutely depressed BD patients and healthy controls exhibited similar hippocampal metabolites concentrations, with no changes after 6 weeks of lithium monotherapy. A significant correlation between antidepressant efficacy and increases in NAA concentration over time was observed. Also, there was a significant positive correlation between the changes in glutamate concentrations over follow-up and plasma lithium levels at endpoint. Mixed effects model analysis revealed a bimodal effect of lithium plasma levels in hippocampal glutamate concentrations: levels of 0.2 to 0.49 mmol/L (n=9) were associated with a decrease in glutamate concentrations, whereas the subgroup of BD subjects with ``standard{''} lithium levels (>= 0.50 mmol/L; n = 10) showed an overall increase in glutamate concentrations over time. Conclusions: These preliminary results suggest that lithium has a bimodal action in hippocampal glutamate concentration depending on the plasma levels. (AU)

• Processo FAPESP: 13/03905-4 - Avaliação de diferenças neurobiológicas entre pacientes com transtorno bipolar subtipos i e ii virgens de tratamento
• Beneficiário: Marcus Vinicius Zanetti
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 09/14891-9 - Avaliação longitudinal dos efeitos neuroprotetores e neurotróficos induzidos pelo lítio no transtorno bipolar: identificação de alvos clinicamente relevantes
• Beneficiário: Rodrigo Machado-Vieira
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores