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Objectives: To investigate the potential role of disease-modifying therapies (DMTs) used to treat multiple sclerosis on inducing brain-derived neurotrophic factor (BDNF) production., Methods: A total of 82 patients entered the study. Sixty (73%) patients were on DMTs (15 on Avonex, 13 on Rebif, 27 on Betaferon, 3 on Mitoxantrone, and 2 on IVIg), whereas 22 received no DMTs. The degree of neurological impairment was recorded using the expanded disability status scale (EDSS). Serum BDNF levels were assessed using the Sandwich ELISA method. We compared mean serum BDNF levels among patient groups based on whether or not they were on DMTs, and the specific agent used. Then, the relationship between BDNF levels and EDSS scores was assessed. The receiver operating characteristic (ROC) curve was used to calculate a cutoff value by which serum BDNF could predict the degree of disability., Results: The study sample had a mean age of 34.6 years, mean EDSS score of 3.8, and mean BDNF level of 198.9 pg/mL. Patients on interferon-β 1b therapy had significantly higher levels of BDNF compared with patients on Mitoxantrone or patients not on DMTs (237.6, 68.6, and 155.9, respectively; P=0.003). The degree of neurological impairment correlated negatively with BDNF levels (P<0.001). A cutoff value of 190 pg/mL was calculated for BDNF (ROC analysis, area under the curve: 0.729, P=0.002). At BDNF levels >190, the sensitivity for a milder degree of neurological impairment (EDSS<3) was 80%., Conclusions: This study showed a significant effect of interferon-β 1b therapy on increasing BDNF production in multiple sclerosis.