Introduction

Major depressive disorder (MDD) is a common mental disorder with unclear pathophysiology 1. Previous studies showed metabolite changes in several small brain structures of depressed patients, although not unequivocally 2, 3. Therefore our study aimed at investigating metabolic alterations associated with MDD within the whole brain.

Methods

Thirty-two patients with MDD and 32 age and gender matched healthy controls underwent 1H-whole brain short-TE spectroscopic imaging. Metabolite concentrations of N-acetylaspartate (NAA), total choline (tCho), total creatine (tCr), glutamine (Gln), glutamate (Glu), and myo-Inositol (mI) over each of eight brain lobes and cerebellum were assessed, with signal normalization using the brain water. The results were compared between patients and controls.

Results

Decreased NAA, tCho, and tCr were found in the right frontal and right parietal lobe in MDD compared to CTRL (10.52 vs. 11.28 for NAA, 2.08 vs. 2.22 for tCho, and 8.98 vs. 9.46 for tCr, p = 0.001 – 0.015), and to a lesser extent in the left frontal lobe (10.71 vs. 11.16 for NAA, 2.09 vs. 2.19 for tCho, and 9.09 vs. 9.48 for tCr, p = 0.046 – 0.068). Furthermore, in MDD increased glutamine was observed in the right frontal (3.38 vs. 2.94, p = 0.014) and left temporal lobe (3.39 vs. 2.95, p = 0.009), and increased glutamate in the cerebellum (7.97 vs. 7.47, p = 0.01).

Discussion

While previous MRS studies in MD patients targeted mostly on small brain areas and reported divergent findings that related to brain regions studied 4-6, as a first study investigating metabolite changes over large brain structures present findings revealed that the lobar brain metabolic alterations associated with MDD were related to brain region and metabolite, and were particularly present in right and left frontal lobes. These alterations may be indicative of neuronal dysfunction (by decreased NAA, tCr and tCho) and altered glutamatergic neuronal activity (by increased Gln in cerebrum and Glu in cerebellum) in patients.

Conclusion

Patients with MDD revealed specific metabolic changes within the whole brain. Future prospective investigations are warranted to study the functional importance of these findings and the pathological reasons behind.

Acknowledgements

This work has been partly support by German Research Foundation.

References

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