title: 31Phosphorus magnetic resonance spectroscopy study of tissue specific changes in high energy phosphates before and after sertraline treatment of geriatric depression.
abstract: BACKGROUND
  We investigated tissue specific differences in markers of energy metabolism, including high energy phosphate compounds (beta and total NTP, PCr) and pH, in older adults with depression compared with healthy controls, before and after a 12-week treatment trial of sertraline.
  
  
  METHODS
  Thirteen older adults, age > or =55, with Major Depressive Disorder (HAMD(17) score of > or =18) were recruited along with ten age-matched controls. The depression subjects had a pre- and post-treatment 4T (31)P-MRS scan using a three-dimensional chemical shift imaging sequence. The extracted brain images were segmented into white matter (WM), gray matter (GM) and CSF. A linear mixed effects model analyzed the effects of pre-treatment and post-treatment depression on phosphorus metabolite concentration estimates (including calculated pH and Mg(++)).
  
  
  RESULTS
  Total tissue beta-NTP (-8%, t(18.66) = 3.50; p = 0.0024) and total tissue total NTP (-6%, t(17.41) = 2.68; p = 0.0156) were lower in subjects with geriatric depression compared with healthy controls. Total tissue levels of total-NTP changed significantly with treatment (-2%, t(14.84) = -2.47; p = 0.0259). Total NTP was reduced in the WM, but not the GM, in the pre-treatment depression group (t(51.65) = 4.02; p = 0.0002). Intracellular pH was higher in the GM of subjects with pre-treatment depression (t(1133.84) = -2.10; p = 0.0353) and decreased to approximate control levels after treatment (t(648.86) = -2.53; p = 0.0115).
  
  
  CONCLUSIONS
  These findings demonstrate bioenergetic changes including tissue specific differences in (31)P-MRS metabolites in geriatric depression. Decreased white matter total NTP may reflect alterations in white matter function.
authors.affiliation: Geriatric Psychiatry Research Program, McLean Hospital, Belmont, MA, USA. bforester@mclean.harvard.edu
authors.forename: Brent P
authors.initials: BP
authors.lastname: Forester
authors.forename: David G
authors.initials: DG
authors.lastname: Harper
authors.forename: J Eric
authors.initials: JE
authors.lastname: Jensen
authors.forename: Caitlin
authors.initials: C
authors.lastname: Ravichandran
authors.forename: Brittany
authors.initials: B
authors.lastname: Jordan
authors.forename: Perry F
authors.initials: PF
authors.lastname: Renshaw
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000378:metabolism; D010755:Organophosphates / Q000378:metabolism*; D010759:Phosphorus Isotopes; D020280:Sertraline / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D010755:Organophosphates; D010759:Phosphorus Isotopes; D020280:Sertraline