Lateralized caudate metabolic abnormalities in adolescent major depressive disorder: a proton MR spectroscopy study

Abstract

Objective: Proton magnetic resonance spectroscopy ((1)H-MRS) has been increasingly used to examine striatal neurochemistry in adult major depressive disorder. This study extends the use of this modality to pediatric major depression to test the hypothesis that adolescents with major depression have elevated concentrations of striatal choline and creatine and lower concentrations of N-acetylaspartate.

Method: Fourteen adolescents (ages 12-19 years, eight female) who had major depressive disorder for at least 8 weeks and a severity score of 40 or higher on the Children's Depression Rating Scale-Revised and 10 healthy comparison adolescents (six female) group-matched for gender, age, and handedness were enrolled. All underwent three-dimensional 3-T (1)H-MRS at high spatial resolution (0.75-cm(3) voxels). Relative levels of choline, creatine, and N-acetylaspartate in the left and right caudate, putamen, and thalamus were scaled into concentrations using phantom replacement, and levels were compared for the two cohorts.

Results: Relative to comparison subjects, adolescents with major depressive disorder had significantly elevated concentrations of choline (2.11 mM versus 1.56 mM) and creatine (6.65 mM versus 5.26 mM) in the left caudate. No other neurochemical differences were observed between the groups.

Conclusions: These findings most likely reflect accelerated membrane turnover and impaired metabolism in the left caudate. The results are consistent with prior imaging reports of focal and lateralized abnormalities in the caudate in adult major depression.

FIGURE 1

Volume of Interest and Slices Outlined on Axial, Sagittal, and Coronal MR Images, Along With Spectra Matrix From One Slice and Maps From Fitted Peak Areas of the Spectra From a 16-Year-Old Girl With Depressiona ^a In panel A, the 7 cm × 10 cm × 6 cm volume of interest is outlined on a T₂-weighted axial image, and the striata and thalami are superimposed onto the image. In panel B, the eight inferior-superior Hadamard spectroscopic imaging-encoded slices are shown within the region of interest on a T₁-weighted sagittal image, with the slice from panel A marked with an arrow. Panel C shows the outline of the volume of interest in a T₁-weighted coronal image; the arrow indicates the location of the slice from panel A. The large image (bottom left) shows part of the 7 cm × 10 cm spectra matrix from the volume-of-interest slice corresponding to the image in panel A, with the striata and thalami locations outlined. Spectra represent 0.75-cm³ voxels, and all are on common frequency and intensity scales. The three images at bottom right show metabolic maps of N-acetylaspartate, choline, and creatine from the fitted peak areas of the spectra on the left.

FIGURE 2

Plots of the 25%, Median, and 75% Ranges (Boxes) and the ±95% Range (Whiskers) of the Lateralization of the Choline and Creatine Concentrations Between the Left and Right Caudate in Adolescents With Major Depressive Disorder and Comparison Subjectsa ^a Significant differences between groups were observed only in the left caudate.