Regional metabolic heterogeneity in anterior cingulate cortex in major depressive disorder: A multi-voxel 1H magnetic resonance spectroscopy study

Background: Previous studies have shown major depressive disorder (MDD) is associated with altered neurometabolites in the anterior cingulate cortex (ACC). However, the regional metabolic heterogeneity in the ACC in individuals with MDD remains unclear. Methods: We recruited 59 first-episode, treatment-naive young adults with MDD and 50 healthy controls who underwent multi-voxel 1H-MRS scanning at 3 T (Tesla) with voxels placed in the ACC, which was divided into two subregions, pregenual ACC (pACC) and anterior midcingulate cortex (aMCC). Between and within-subjects metabolite concentration variations were analyzed with SPSS. Results: Compared with control subjects, patients with MDD exhibited higher glutamate (Glu) and glutamine (Gln) levels in the pACC and higher myo-inositol (MI) level in the aMCC. We observed higher Glu and Gln levels and lower N-acetyl-aspartate (NAA) level in the pACC than those in the aMCC in both MDD and healthy control (HC) groups. More importantly, the metabolite concentration gradients of Glu, Gln and NAA were more pronounced in MDD patients relative to HCs. In the MDD group, the MI level in the aMCC positively correlated with the age of onset. Limitations: The use of the relative concentration of metabolites constitutes a key study limitation. Conclusions: We observed inconsistent alterations and distribution of neuro-metabolites concentration in the pACC and aMCC, revealing regional metabolic heterogeneity of ACC in first-episode, treatment-naive young individuals with MDD. These results provided new evidence for abnormal neuro-metabolites of ACC in the pathophysiology of MDD and suggested that pACC and aMCC might play different roles in MDD.

Automated summary

This study found regional metabolic heterogeneity in the anterior cingulate cortex (ACC) in first-episode, treatment-naive individuals with major depressive disorder (MDD). Compared to healthy controls, patients with MDD exhibited higher levels of glutamate (Glu) and glutamine (Gln) in the pregenual ACC (pACC) and higher levels of myo-inositol (MI) in the anterior midcingulate cortex (aMCC). In addition, the metabolite concentration gradients of Glu, Gln, and N-acetyl-aspartate (NAA) were more pronounced in MDD patients. These findings provide new evidence for abnormal neuro-metabolites in the ACC in MDD and suggest differential roles of pACC and aMCC in the disorder.