Abstract
BACKGROUND: Major depressive disorder (MDD) is a common and disabling condition associated with significant cognitive impairments that persist over the long term, affecting patients' social function. Traditional cognitive testing methods are time-consuming and subjective. This study investigates whether resting motor threshold (RMT), a neurophysiological measure of motor cortical excitability, can predict cognitive function in drug-naive patients with MDD, with a focus on sex-specific differences. METHODS: This cross-sectional study enrolled 158 first-episode, drug-naive patients with MDD from August 2023 to April 2024. Participants underwent comprehensive cognitive assessments using the MATRICS Consensus Cognitive Battery (MCCB) and transcranial magnetic stimulation (TMS) to measure RMT. Hormone levels were also assessed. The study was approved by the hospital's Ethics Committee and conducted in accordance with the Declaration of Helsinki. Statistical analysis included bivariate correlation and multiple regression analyses to identify factors associated with cognitive function. RESULTS: A total of 138 subjects completed the study. The mean age was 19.28 ± 6.84 years, with 41 males (29.7%) and 97 females (70.3%). In the overall sample, higher right RMT was associated with better attention/vigilance (CPT-IP) performance. In male patients, higher left RMT was associated with lower verbal learning (HVLT-R) scores, while higher right RMT was associated with higher HVLT-R scores. No significant correlations were found in female patients. Multiple regression analyses showed that these relationships were independent of age, education, and hormone levels. CONCLUSIONS: This exploratory study is the first to demonstrate that RMT can predict verbal learning ability, attention, and vigilance in male patients with MDD, whereas no significant correlation was observed in female patients. This finding reveals RMT's potential significance and highlights that sex differences necessitate consideration when developing rTMS-based treatment regimens targeting both antidepressant and cognitive outcomes. Further longitudinal studies with larger sample sizes are needed to validate its clinical relevance.