Unravelling Structural and Metabolic Alterations in the Hippocampus and Anterior Cingulate Cortex Using Integrated MRI and MRS in Major Depressive Disorder

The present study investigated structural and metabolic changes in the two brain regions of the limbic system, right hippocampus and anterior cingulate cortex (ACC), implicated in the pathophysiology of major depressive disorder (MDD). Three-dimensional-T1-weighted magnetic resonance imaging (MRI) and single-voxel in vivo magnetic resonance spectroscopy (MRS) were performed on a 3.0 T MRI in patients with MDD (n = 64) and healthy controls (HC, n = 47). The severity of depression was assessed using clinical scales (Hamilton Depression Rating Score [HDRS] and Montgomery-Åsberg Depression Rating Score [MDRS]). The automated volumetric segmentation of the T1-weighted MR images was performed using Freesurfer 7.2.0. The tissue-corrected concentration of neurochemicals was quantified using Osprey software. The relationship between hippocampal and ACC metabolite levels was examined with their volumes. Additionally, the levels of neurochemicals and volumes were correlated with the severity of depression. After adjusting for multiple comparisons using the false discovery rate (FDR), the concentration of total NAA (t-NAA, N-acetyl aspartate+ N-acetyl-aspartyl-glutamate [NAAG]), myoinositol (mI), total choline (tCho) and total creatine (tCr) were significantly reduced (p_FDR < 0.05) in the hippocampus of the MDD patients. The ACC in MDD patients showed significantly higher levels of tNAA and tCr (p_FDR < 0.05). Further, the volume of ACC was significantly increased in patients with MDD. Although hippocampal volume was not different between the two groups, a weak positive correlation was observed between the tCho levels and the volumes of the hippocampus and mid-ACC. Hippocampal glutamate + glutamine (Glx) levels showed a weak negative correlation with the MDRS score, whereas ACC tCho showed a negative correlation with the HDRS score. Our observations suggested that the pathophysiology of MDD is not only associated with hippocampal neurodegeneration but may also involve glial proliferation, leading to increased ACC volume. These changes might alter neurotransmission in the limbic system, contributing to the pathophysiology of depression.