Mass spectrometry approaches for monitoring therapeutic response in major depressive disorder.

Major depressive disorder (MDD) is a complex and disabling psychiatric condition, often chronic and recurrent, for which treatment selection remains largely guided by trial-and-error. Objective biomarkers capable of predicting and monitoring therapeutic response are urgently needed to enable personalized interventions and reduce exposure of the patients to ineffective treatments. Mass spectrometry (MS) has emerged as a central analytical technique, providing the sensitivity and specificity required to capture multi-parametric molecular signatures in biofluids such as plasma, serum, cerebrospinal fluid, and urine. In this context, this review summarizes the application of MS-based platforms to characterize molecular changes associated with treatment response in MDD and discusses how integrative multi-omics approaches can generate robust insights into treatment efficacy and resistance. We highlight current applications, discuss opportunities for MS-guided monitoring of therapeutic strategies, and outline how convergent molecular signatures may accelerate the development of clinically informative biomarkers for precision psychiatry in MDD.