title: Dorsal Anterior Cingulate Lactate and Glutathione Levels in Euthymic Bipolar I Disorder: 1H-MRS Study.
abstract: Oxidative stress and mitochondrial dysfunction are 2 closely integrated processes implicated in the physiopathology of bipolar disorder. Advanced proton magnetic resonance spectroscopy techniques enable the measurement of levels of lactate, the main marker of mitochondrial dysfunction, and glutathione, the predominant brain antioxidant. The objective of this study was to measure brain lactate and glutathione levels in bipolar disorder and healthy controls.
  
  
  
  Eighty-eight individuals (50 bipolar disorder and 38 healthy controls) underwent 3T proton magnetic resonance spectroscopy in the dorsal anterior cingulate cortex (2x2x4.5cm(3)) using a 2-D JPRESS sequence. Lactate and glutathione were quantified using the ProFit software program.
  
  
  
  Bipolar disorder patients had higher dorsal anterior cingulate cortex lactate levels compared with controls. Glutathione levels did not differ between euthymic bipolar disorder and controls. There was a positive correlation between lactate and glutathione levels specific to bipolar disorder. No influence of medications on metabolites was observed.
  
  
  
  This is the most extensive magnetic resonance spectroscopy study of lactate and glutathione in bipolar disorder to date, and results indicated that euthymic bipolar disorder patients had higher levels of lactate, which might be an indication of altered mitochondrial function. Moreover, lactate levels correlated with glutathione levels, indicating a compensatory mechanism regardless of bipolar disorder diagnosis.
authors.affiliation: Mood Disorders Unit (GRUDA), Institute of Psychiatry, School of Medicine (IPq-FMUSP) (Drs Soeiro-de-Souza and Moreno), Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology (InRad-FMUSP) (Drs Pastorello, Costa Leite, and Otaduy), and Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine (Dr Soeiro-de-Souza), University of São Paulo (IPq-FMUSP), São Paulo, Brazil; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (Dr Henning); Max Planck Institute of Biological Cybernetics, Tubingen, Germany (Dr Henning). marciogss@gmail.com.
authors.forename: Márcio Gerhardt
authors.initials: MG
authors.lastname: Soeiro-de-Souza
authors.affiliation: Mood Disorders Unit (GRUDA), Institute of Psychiatry, School of Medicine (IPq-FMUSP) (Drs Soeiro-de-Souza and Moreno), Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology (InRad-FMUSP) (Drs Pastorello, Costa Leite, and Otaduy), and Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine (Dr Soeiro-de-Souza), University of São Paulo (IPq-FMUSP), São Paulo, Brazil; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (Dr Henning); Max Planck Institute of Biological Cybernetics, Tubingen, Germany (Dr Henning).
authors.forename: Bruno F
authors.initials: BF
authors.lastname: Pastorello
authors.affiliation: Mood Disorders Unit (GRUDA), Institute of Psychiatry, School of Medicine (IPq-FMUSP) (Drs Soeiro-de-Souza and Moreno), Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology (InRad-FMUSP) (Drs Pastorello, Costa Leite, and Otaduy), and Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine (Dr Soeiro-de-Souza), University of São Paulo (IPq-FMUSP), São Paulo, Brazil; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (Dr Henning); Max Planck Institute of Biological Cybernetics, Tubingen, Germany (Dr Henning).
authors.forename: Cláudia da Costa
authors.initials: Cda C
authors.lastname: Leite
authors.affiliation: Mood Disorders Unit (GRUDA), Institute of Psychiatry, School of Medicine (IPq-FMUSP) (Drs Soeiro-de-Souza and Moreno), Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology (InRad-FMUSP) (Drs Pastorello, Costa Leite, and Otaduy), and Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine (Dr Soeiro-de-Souza), University of São Paulo (IPq-FMUSP), São Paulo, Brazil; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (Dr Henning); Max Planck Institute of Biological Cybernetics, Tubingen, Germany (Dr Henning).
authors.forename: Anke
authors.initials: A
authors.lastname: Henning
authors.affiliation: Mood Disorders Unit (GRUDA), Institute of Psychiatry, School of Medicine (IPq-FMUSP) (Drs Soeiro-de-Souza and Moreno), Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology (InRad-FMUSP) (Drs Pastorello, Costa Leite, and Otaduy), and Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine (Dr Soeiro-de-Souza), University of São Paulo (IPq-FMUSP), São Paulo, Brazil; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (Dr Henning); Max Planck Institute of Biological Cybernetics, Tubingen, Germany (Dr Henning).
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Moreno
authors.affiliation: Mood Disorders Unit (GRUDA), Institute of Psychiatry, School of Medicine (IPq-FMUSP) (Drs Soeiro-de-Souza and Moreno), Laboratory of Magnetic Resonance LIM44, Department and Institute of Radiology (InRad-FMUSP) (Drs Pastorello, Costa Leite, and Otaduy), and Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine (Dr Soeiro-de-Souza), University of São Paulo (IPq-FMUSP), São Paulo, Brazil; Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland (Dr Henning); Max Planck Institute of Biological Cybernetics, Tubingen, Germany (Dr Henning).
authors.forename: Maria Concepción
authors.initials: MC
authors.lastname: Garcia Otaduy
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006179:Gyrus Cinguli / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D019344:Lactic Acid; D005978:Glutathione
keywords: bipolar disorder; glutathione; lactate; mitochondrial disease; oxidative stress