Abnormal Anterior Cingulate N-Acetylaspartate and Executive Functioning in Treatment-Resistant Depression After rTMS Therapy

Background: Cognitive impairment is a key feature of treatment-resistant depression (TRD) and can be related to the anterior cingulate cortex (ACC) function. Repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the last two decades. However, no studies to date have investigated the association between neurobiochemical changes within the anterior cingulate and executive dysfunction measured in TRD being treated with rTMS. Methods: Thirty-two young depressed patients with treatment-resistant unipolar depression were enrolled in a double-blind, randomized study [active (n=18) vs. sham (n=14)]. ACC metabolism was investigated before and after high-frequency (15Hz) rTMS using 3-tesla proton magnetic resonance spectroscopy (1H-MRS). The results were compared with 28 age- and gender-matched healthy controls. Executive functioning was measured with the Wisconsin Card Sorting Test (WCST) among 34 subjects with TRD and 28 healthy subjects. Results: Significant reductions in N-acetylaspartate (NAA) and choline-containing Compound levels in the left ACC were found in subjects with TRD pre-rTMS when compared with healthy controls. After successful treatment, NAA levels increased significantly in the left ACC of subjects and were not different from those of age-matched controls. In the WCST, more perseverative errors and fewer correct numbers were observed in TRD subjects at baseline. Improvements in both perseverative errors and correct numbers occurred after active rTMS. In addition, improvement of perseverative errors was positively correlated with enhancement of NAA levels in the left ACC in the active rTMS group. Conclusions: Our results suggest that the NAA concentration in the left ACC is associated with an improvement in cognitive functioning among subjects with TRD response to active rTMS.