Proton MR spectroscopy of the hippocampus at 3 Tesla in patients with major depression under pharmacological treatment

Purpose: In several studies, proton magnetic resonance spectroscopy (1H-MRS) revealed varying metabolic alterations in different brain regions which are involved in emotional processing. Most of these studies performed MRS in the frontal lobe, basal ganglia or cingulum, only a few dealt with the hippocampus or amygdala regions. Because of the important role of the medial temporal lobe in the pathogenesis of depression, MRS of the hippocampus was performed at 3.0 T before and after medical treatment.

Material and methods Examinations were done on our clinical 3T whole-body MR system (Gyroscan Achieva 3.0 T, Philips Medical Systems) with a transmit/receive head coil designed for MRI and MRS. We studied patients with major depression (n=18) before, and 6–8 weeks (n=11) after standard pharmacological treatment.

Single-volume 1H-MRS of a 6ml VOI placed in the left hippocampus was performed including acquisition of water-suppressed PRESS spectra with TE/TR 140/2000 ms and 30/2000 ms. Absolute and relative metabolite concentrations of N-acetyl-aspartate (NAA), of total creatine (tCr), of choline (Cho) and of inositol (Ins) containing compounds, glutamine (Gln) and glutamine/glutamate/GABA (Glx) were calculated using the unsuppressed water signal of the VOI as an internal reference.

Data were compared to findings of 10 sex- and age-matched healthy controls. Group comparisons between patients and healthy controls were performed by analysis of variance using age and gender as covariates. Treatment effects were analyzed with a nonparametric Wilcoxon match pairs test. Correlations of metabolite parameters and depression severity determined by the Beck Depression Inventory (BDI) Rating Scale were tested by Pearson correlation analysis.

Results: Pre-medication concentrations of total creatine and of relative Glx and Gln were significantly reduced in the hippocampus in the patient group compared to healthy controls. Absolute NAA and Cho seem to be slightly reduced; however, differences did not reach statistical significance. No changes were observed in inositol containing compounds.

Correlation analysis of depression severity vs. MRS showed a significant correlation (r=-0.675, p=0.006) between NAA/Ins and BDI. Intra-individual comparison of pre- and post-medication examinations showed a trend towards recovery of [NAA] and [Cho]; no changes were found for relative Glx or Gln. A significant negative correlation was found between δ values (post- minus pre-medication) of BDI and [NAA] (r=-0.615, p=0.044) and [Cho] (r=-0.762, p=0.006). That means, patients with improvement in depression rating score (decline in BDI) showed an increase in absolute hippocampal NAA and choline concentration after treatment.

Conclusion: In accordance with findings obtained in other brain areas, we found a significant reduction in relative Glx concentrations in the medial temporal lobe of untreated patients, indicating a disturbed glutamergic metabolism in major depression disorder. Decreased NAA/Ins correlates well with the severity of depression. NAA and Cho recovery suggests that these alterations are reversible in patients who respond to treatment.

MRS at 3T using smaller target voxels is able to detect even discrete changes in brain metabolite concentrations. Therefore highfield MRS has a particular potential in therapy follow-up studies where expected alterations are rather small.