Altered neurometabolite levels in the brains of patients with depression: A systematic analysis of magnetic resonance spectroscopy studies

Background: Numerous magnetic resonance spectroscopy (MRS) studies have reported metabolic abnormalities in the brains of patients with depression, although inconsistent results have been reported. The aim of this study was to explore changes in neurometabolite levels in patients with depression across large-scale MRS studies. Method: A total of 307 differential metabolite entries associated with depression were retrieved from 180 MRS studies retrieved from the Metabolite Network of Depression Database. The vote-counting method was used to identify consistently altered metabolites in the whole brain and specific brain regions of patients with depression. Results: Only few differential neurometabolites showed a stable change trend. The levels of total choline (tCho) and the tCho/N-acetyl aspartate (NAA) ratio were consistently higher in the brains of patients with depression, and that the levels of NAA, glutamate and glutamine (Glx), and gamma-aminobutyric acid (GABA) were lower. For specific brain regions, we found lower Glx levels in the prefrontal cortex and lower GABA concentrations in the occipital cortex. We also found lower concentrations of NAA in the anterior cingulate cortex and prefrontal cortex. The levels of tCho were higher in the prefrontal cortex and putamen. Conclusion: Our results revealed that most altered neurometabolites in previous studies lack of adequate reproducibility. Through vote-counting method with large-scale studies, downregulation of glutamatergic neu-rometabolites, impaired neuronal integrity, and disturbed membrane metabolism were found in the pathobiology of depression, which contribute to existing knowledge of neurometabolic changes in depression. Further studies based on a larger dataset are needed to confirm our findings.

Automated summary

Through large-scale magnetic resonance spectroscopy studies, changes in neurometabolite levels in patients with depression were explored. Consistent alterations were found in the levels of total choline and the tCho/N-acetyl aspartate ratio, which were higher, and in the levels of NAA, glutamate and glutamine, and gamma-aminobutyric acid, which were lower. Specific brain regions also showed altered neurometabolite levels, such as lower glutamate levels in the prefrontal cortex and lower GABA concentrations in the occipital cortex. These findings contribute to our understanding of neurometabolic changes in depression.