title: Hippocampal abnormalities of glutamate/glutamine, N-acetylaspartate and choline in patients with depression are related to past illness burden.
abstract: BACKGROUND
  Smaller hippocampal volumes in major depressive disorder (MDD) have been linked with earlier onset, previous recurrences and treatment refractoriness. The aim of our study was to investigate metabolite abnormalities in the hippocampus associated with past depressive illness burden.
  
  
  METHODS
  Glutamate/glutamine (Glx), N-acetylaspartate (NAA) and choline (Cho), potential markers of glial/neuronal integrity and membrane turnover, respectively, were measured in adults with depression and healthy controls using a 3 T magnetic resonance spectroscopy scanner. Voxels were placed in the head of the right and left hippocampus. We controlled for systematic differences resulting from volume-of-interest (VOI) tissue composition and total hippocampal volume.
  
  
  RESULTS
  Our final sample comprised a total of 16 healthy controls and 52 adult patients with depression in different stages of the illness (20 treatment-resistant/chronic, 18 remitted-recurrent and 14 first-episode), comparable for age and sex distribution. Patients with treatment-resistant/chronic and remitted-recurrent depression had significantly lower levels of Glx and NAA than controls, especially in the right hippocampal region (p ≤ 0.025). Diminished levels of Glx were correlated with longer illness duration (left VOI r = -0.34, p = 0.01). By contrast, Cho levels were significantly higher in patients with treatment-resistant/chronic depression than those with first-episode depression or controls in the right and left hippocampus (up to 19% higher; all p ≤ 0.025) and were consistently related to longer illness duration (right VOI r = 0.30, p = 0.028; left VOI r = 0.38, p = 0.004) and more previous episodes (right VOI r = 0.46, p = 0.001; left VOI r = 0.44, p = 0.001).
  
  
  CONCLUSIONS
  The cross-sectional design and the inclusion of treated patients are the main limitations of the study.
  
  
  CONCLUSIONS
  Our results support that metabolite alterations within the hippocampus are more pronounced in patients with a clinical evolution characterized by recurrences and/or chronicity and add further evidence to the potential deleterious effects of stress and depression on this region.
authors: Department of Psychiatry, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Institut d'Investigació Biomèdica Sant Pau (IIB Sant Pau), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain.
authors: Javier
authors: J
authors: de Diego-Adeliño
authors: Maria J
authors: MJ
authors: Portella
authors: Beatriz
authors: B
authors: Gómez-Ansón
authors: Olga
authors: O
authors: López-Moruelo
authors: Maria
authors: M
authors: Serra-Blasco
authors: Yolanda
authors: Y
authors: Vives
authors: Dolors
authors: D
authors: Puigdemont
authors: Rosario
authors: R
authors: Pérez-Egea
authors: Enric
authors: E
authors: Álvarez
authors: Víctor
authors: V
authors: Pérez
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D016022:Case-Control Studies; D002794:Choline / Q000378:metabolism*; D017281:Cost of Illness; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000378:metabolism*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate; D002794:Choline