Focal and lateralized subcortical abnormalities in unipolar major depressive disorder: an automated multivoxel proton magnetic resonance spectroscopy study

Biol Psychiatry. 2003 Oct 1;54(7):744-50. doi: 10.1016/s0006-3223(02)01908-x.


Background: The results of prior proton magnetic resonance spectroscopy ((1)H-MRS) studies in unipolar major depressive disorder (MDD) evaluating choline (Cho)/creatine (Cr) and N-acetyl-L-aspartate (NAA)/Cr ratios are mixed. These single-voxel or one-dimensional chemical-shift imaging (CSI) nonautomated (1)H-MRS studies has been unable to evaluate global or lateralized abnormalities in neuronal or membrane function. Using automated multivoxel two-dimensional CSI (1)H-MRS techniques, we tested the hypothesis that patients with MDD have focal neuronal and membrane abnormalities localized in the subcortical region.

Methods: Whole brain and subcortical measures of Cho, NAA, Cr, and myo-inositol (mI) were obtained in 18 patients with MDD and 20 control subjects using automated two-dimensional CSI (1)H-MRS.

Results: Compared with control subjects, MDD patients had a significantly lower mean NAA/Cr amplitude in the caudate and a significantly higher mean Cho/Cr amplitude in the putamen, particularly on the right side. No differences were observed for global whole brain measurements.

Conclusions: The findings support reduced neuronal viability or function in the caudate and altered membrane phospholipid metabolism in the putamen for patients with MDD. Our results are consistent with prior magnetic resonance imaging, positron emission tomography, and postmortem reports of focal and lateralized abnormalities of the basal ganglia in MDD.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aspartic Acid / analogs & derivatives*
  • Aspartic Acid / analysis
  • Brain / metabolism*
  • Brain / pathology
  • Brain Chemistry*
  • Brain Mapping
  • Choline / analysis
  • Creatine / analysis
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / metabolism
  • Female
  • Humans
  • Inositol / analysis
  • Magnetic Resonance Imaging / instrumentation
  • Magnetic Resonance Imaging / methods
  • Magnetic Resonance Spectroscopy*
  • Male
  • Middle Aged
  • Protons*
  • Psychiatric Status Rating Scales
  • Radionuclide Imaging


  • Protons
  • Aspartic Acid
  • Inositol
  • N-acetylaspartate
  • Creatine
  • Choline