title: Hippocampal neurochemical markers in bipolar disorder patients following the first-manic episode: A prospective 12-month proton magnetic resonance spectroscopy study.
abstract: OBJECTIVE
  Previous studies reported decreased N-acetyl aspartate and increased Glx (the sum of glutamate plus glutamine) in bipolar disorder. Since these studies included patients at different stages of illness, it is unknown whether these changes have a causal role or a consequence of multiple episodes and treatments. The studies in early-stage bipolar disorder patients have the potential to provide answers to these issues. Therefore, we evaluated N-acetyl aspartate and Glx levels in hippocampi of first-episode bipolar disorder patients and health subjects at baseline and at 12 months, and examined the impact of episode recurrence on these measures.
  
  
  METHODS
  We used single-voxel proton magnetic resonance spectroscopy to compare the hippocampal neurometabolites ( N-acetyl aspartate and Glx) levels between 41 patients with bipolar disorder following recovery from their first-manic episode and 27 matched healthy subjects at recruitment and 12 months later. We also compared N-acetyl aspartate and Glx levels between patients who had a recurrence of a mood episode and those who did not.
  
  
  RESULTS
  There was no main effect of either group (diagnosis) or time for hippocampal N-acetyl aspartate and Glx levels in bipolar disorder patients and healthy subjects. We also did not find any group-by-time interaction for the levels of these metabolites. There were also no differences in N-acetyl aspartate and Glx between patients who experienced a recurrence of a mood episode and those who did not over 12-month follow-up.
  
  
  CONCLUSIONS
  Our data suggest that N-acetyl aspartate and Glx levels are not altered in early stage bipolar disorder. Further, these data suggest that episode recurrence in early stages does not have a significant impact on the levels of these metabolites. These may suggest that there may be an early window for intervention to potentially arrest neuroprogression of the disease.
authors.affiliation: 1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.|2 Laboratory of Molecular Psychiatry, Centro de Pesquisas Experimentais, Hospital de Clínicas de Porto Alegre, and INCT for Translational Medicine, Porto Alegre, Brazil.|3 Postgraduate Program in Medicine: Psychiatry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Leonardo E
authors.initials: LE
authors.lastname: Silveira
authors.affiliation: 1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.|4 Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Bond
authors.affiliation: 5 Division of Neurology, Department of Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Erin Leigh
authors.initials: EL
authors.lastname: MacMillan
authors.affiliation: 1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jan-Marie
authors.initials: JM
authors.lastname: Kozicky
authors.affiliation: 1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.|6 Department of Psychiatry, National Institute of Mental Health and Neuro Sciences (NIMHANS), Bangalore, India.
authors.forename: Kesavan
authors.initials: K
authors.lastname: Muralidharan
authors.affiliation: 1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.|2 Laboratory of Molecular Psychiatry, Centro de Pesquisas Experimentais, Hospital de Clínicas de Porto Alegre, and INCT for Translational Medicine, Porto Alegre, Brazil.
authors.forename: Joana
authors.initials: J
authors.lastname: Bücker
authors.affiliation: 2 Laboratory of Molecular Psychiatry, Centro de Pesquisas Experimentais, Hospital de Clínicas de Porto Alegre, and INCT for Translational Medicine, Porto Alegre, Brazil.|7 Department of Pharmacology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Adriane Ribeiro
authors.initials: AR
authors.lastname: Rosa
authors.affiliation: 2 Laboratory of Molecular Psychiatry, Centro de Pesquisas Experimentais, Hospital de Clínicas de Porto Alegre, and INCT for Translational Medicine, Porto Alegre, Brazil.
authors.forename: Flavio
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: 1 Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Lakshmi N
authors.initials: LN
authors.lastname: Yatham
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001714:Bipolar Disorder / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D011446:Prospective Studies; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D055815:Young Adult
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: Bipolar disorder; first mania; hippocampus; metabolites; spectroscopy