title: A Longitudinal (6-week) 3T (1)H-MRS Study on the Effects of Lithium Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression.
abstract: The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no longitudinal study has specifically evaluated lithium׳s effects on ACC metabolites using (1)H-MRS, as well as its association with clinical improvement in bipolar depression. This (1)H-MRS (TE=35ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NAA), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate+glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (mI/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium׳s therapeutic effects in BD.
authors.affiliation: 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; Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH, Bethesda, MD, United States. Electronic address: machadovieirar@mail.nih.gov.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Machado-Vieira
authors.affiliation: 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.forename: Wagner F
authors.initials: WF
authors.lastname: Gattaz
authors.affiliation: 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.forename: Marcus V
authors.initials: MV
authors.lastname: Zanetti
authors.affiliation: 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; Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH, Bethesda, MD, United States.
authors.forename: Rafael T
authors.initials: RT
authors.lastname: De Sousa
authors.affiliation: Department of Clinical Medicine and Translational Psychiatry Research Group Faculty of Medicine Federal University of Ceara, Fortaleza, Brazil.
authors.forename: Andre F
authors.initials: AF
authors.lastname: Carvalho
authors.affiliation: Mood Disorders Program, GRUDA, Department of Psychiatry, University of Sao Paulo, Brazil.
authors.forename: Marcio G
authors.initials: MG
authors.lastname: Soeiro-de-Souza
authors.affiliation: Laboratory of Magnetic Resonance in Neuroradiology, LIM- 44, Institute and Department of Radiology, University of Sao Paulo, Brazil.
authors.forename: Claudia C
authors.initials: CC
authors.lastname: Leite
authors.affiliation: Laboratory of Magnetic Resonance in Neuroradiology, LIM- 44, Institute and Department of Radiology, University of Sao Paulo, Brazil.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Otaduy
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006179:Gyrus Cinguli / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D021621:Imaging, Three-Dimensional; D007294:Inositol / Q000378:metabolism; D018020:Lithium Compounds / Q000627:therapeutic use; D008137:Longitudinal Studies; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011522:Protons; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D018020:Lithium Compounds; D011522:Protons; D005973:Glutamine; D018698:Glutamic Acid; D007294:Inositol
keywords: Bipolar disorder; Depression; Glutamate; Imaging; Lithium; Magnetic resonance spectroscopy