title: A pilot study of hippocampal N-acetyl-aspartate in youth with treatment resistant major depression.
abstract: Smaller hippocampal volumes, as assessed by magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) indexed alterations in brain metabolites have been identified in adults with major depressive disorder (MDD). Our group has found similar effects in MDD youth. However, this has not been studied in youth with treatment resistant MDD (TRD), nor has the interaction between regional N-acetyl-aspartate and volume deficits. N-acetyl-aspartate is an amino acid in the synthesis pathway of glutamate, and serves a marker of neuronal viability/number.
  
  
  
  Fifteen typically developing youth (16-22 years of age; 7 males, 8 females) and eighteen youth with TRD (14-22 years of age; 8 males, 10 females) underwent1H-MRS and MRI on a 3T scanner. A short echo PRESS protocol was used with voxels in the right and left hippocampi (6mL each). Hippocampal volume was evaluated using FreeSurfer.
  
  
  
  Compared with the typically developing group, youth with TRD had lower concentrations of N-acetyl-aspartate in the left hippocampus (p=0.004), and a trend for smaller left hippocampal volume (p=0.067). In TRD subjects, hippocampal N-acetyl-aspartate was inversely correlated with left (r=-0.68, p=0.003) but not right hippocampal volume. Right hippocampal glutamate+glutamine was greater in TRD youth compared to typically developing controls (p=0.007).
  
  
  
  These results suggest a neurochemical and structural deficit in the hippocampi of youth with TRD. These findings fit with the role of N-acetyl-aspartate in glutamate neurotransmission and the effect of glutamate on brain morphology.
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Lefebvre
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada.
authors.forename: Lisa Marie
authors.initials: LM
authors.lastname: Langevin
authors.affiliation: Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Canada; Department of Psychiatry, McGill University, Canada.
authors.forename: Natalia
authors.initials: N
authors.lastname: Jaworska
authors.affiliation: Department of Radiology, University of Calgary, Canada; Child and Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital Research Institute, Canada.
authors.forename: Ashley D
authors.initials: AD
authors.lastname: Harris
authors.affiliation: GE Healthcare, Calgary, Canada; Department of Radiology, University of Calgary, Canada; Child and Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital Research Institute, Canada.
authors.forename: R Marc
authors.initials: RM
authors.lastname: Lebel
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada.
authors.forename: Yamile
authors.initials: Y
authors.lastname: Jasaui
authors.affiliation: Department of Pediatrics, University of Calgary, Canada; Department of Clinical Neurosciences, University of Calgary, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Kirton
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada.
authors.forename: T Christopher
authors.initials: TC
authors.lastname: Wilkes
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada.
authors.forename: Mariko
authors.initials: M
authors.lastname: Sembo
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada.
authors.forename: Rose
authors.initials: R
authors.lastname: Swansburg
authors.affiliation: Department of Psychiatry, University of Calgary, Canada; Department of Pediatrics, University of Calgary, Canada; Strategic Clinical Network for Addictions and Mental Health, Alberta Health Services, Canada; Mathison Centre for Mental Health Research & Education, Hotchkiss Brain Institute, Canada; Child and Adolescent Imaging Research (CAIR) Program, Alberta Children's Hospital Research Institute, Canada. Electronic address: fmacmast@ucalgary.ca.
authors.forename: Frank P
authors.initials: FP
authors.lastname: MacMaster
mesh_terms: D000293:Adolescent; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000378:metabolism*; D061218:Depressive Disorder, Treatment-Resistant / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010865:Pilot Projects; D066244:Proton Magnetic Resonance Spectroscopy; D055815:Young Adult
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
keywords: Adolescent; Depression; Glutamate; Hippocampus; Magnetic Resonance Spectroscopy; N-Acetyl-Aspartate