High-frequency rTMS treatment increases left prefrontal myo-inositol in young patients with treatment-resistant depression

Abstract

Background Neuroimaging studies suggest that the prefrontal cortex (PFC) is involved in the pathophysiology of major depression. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. In this study metabolic changes within PFC of severely depressed patients before and after rTMS were evaluated by proton magnetic resonance spectroscopy (1H-MRS). Method Thirty-four young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study〔active ((n = 19) vs. sham(n = 15)), and the PFC was investigated before and after high-frequency (15 Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy. Response was defined as a 50% reduction of the Hamilton depression rating scale. The results were compared with 28 age- and gender-matched healthy controls. Results In depressive patients a significant reduction in myo-inositol (m-Ino) was observed pre-rTMS ( p < 0.001). After successful treatment, m-Ino increased significantly in left PFC and the levels no longer differed from those of age-matched controls. In addition to a positive correlation between clinical improvement and an increment in m-Ino ratio, a correlation between clinical improvement and early age onset was observed. Conclusions Our results support the notion that major depressive disorder is accompanied by state-dependent metabolic alterations, especially in myo-inositol metabolism, which can be partly reversed by successful rTMS.