Hippocampal metabolites illustrate greater potential for early response assessment to antidepressant therapy than the anterior cingulate cortex in major depressive disorder.
Major Depressive Disorder (MDD) is a psychiatric disorder associated with altered neuro-metabolism. This study investigated the effect of antidepressant therapy on the metabolism of the right hippocampus and anterior cingulate cortex (ACC) in patients with MDD, using in vivo proton magnetic resonance spectroscopy (MRS) at 3.0 T. MRS was performed in 42 patients with MDD (at baseline and after 8 weeks of antidepressant therapy) and 35 healthy controls (HCs). Metabolite concentrations were quantified using Osprey software with partial-volume corrections. The Hamilton Depression Rating Scale (HDRS) was used to assess response to antidepressant therapy. Patients with MDD who had a > 50% reduction in HDRS scores were classified as remitted, and those with a < 50% reduction were grouped as non-remitted after therapy. Compared with HCs, baseline levels of hippocampal total N-acetylaspartate (tNAA), total creatine (tCr), total choline (tCho), and myo-inositol (mI) were reduced. Baseline levels of ACC tNAA and tCr were higher in patients with MDD than in HCs. After antidepressant therapy, a significant increase in tNAA and tCr levels was observed in the hippocampus of patients with remitted MDD, indicating a positive impact of therapy on energy metabolism and neurodegenerative processes, thereby supporting remission. Hippocampal metabolite levels remained unaltered after therapy in the non-remitted subgroup. ACC metabolites remained unaltered after therapy in both remitted and non-remitted subgroups. Thus, findings highlighted the importance of hippocampal metabolism in MDD and the possibility that metabolite levels may serve as biomarkers of antidepressant therapy response.