Could thyrotropin serum level characterize major depressive disorder phenotype? A systematic review and meta-analysis

Purpose: Aim of this systematic review is to evaluate if and how thyrotropin (TSH) serum level levels may influence major depressive disorders (MDD) in drug naïve patients, and if it could characterize MDD phenotype. Methods: A PubMed/MEDLINE, Scopus and Web of Science databases was researched up to January 2025. The studies eligible addressed the questions define based on the PICO framework: (1) Are TSH levels different between first episode drug-naïve (FEDN) patients diagnosed with MDD and healthy subjects? (2) What are the TSH levels in FEDN patients diagnosed with MDD who attempt suicide compared to who do not? This review followed PRISMA guidelines. The quality assessment and the risk of bias were analyzed using QUADAS-2. Results: We included 45 studies in the qualitative synthesis, and 18 in the quantitative one, encompassing a total of 34,448 participants. Our systematic review showed conflicting data about TSH levels in FEDN MDD patients compared to healthy subjects. However, the meta-analysis showed in 6,224 patients that higher TSH levels are related to an increased risk of suicide attempt (Standardized Mean Difference = 1.848 mIU/L, C.I. 95%:1.506 to 2.190) with moderate-high heterogeneity across studies (I2 = 67%, p =.009). Conclusion: We showed conflicting data about TSH levels in FEDN MDD patients compared to healthy subjects. On the contrary, the meta-analysis evidenced significant higher TSH levels among MDD patients with suicide attempt than those without it. The clinical implications of this finding have yet to be established.