SYSTEMATIC REVIEW article
Front. Endocrinol.
Sec. Thyroid Endocrinology
Volume 16 - 2025 | doi: 10.3389/fendo.2025.1580854
This article is part of the Research TopicBipolar Disorder: Where are we now? Treatment Response, Neural Correlates and PersonalityView all 3 articles
Thyrotropin Levels in First-Episode Bipolar Disorder and Their Association with Clinical Phenotypes: Systematic Review and Meta-Analysis systematic review and meta-analysis
Provisionally accepted
Elisa Gatta1
Virginia Maltese2
Francesco Dondi1
Pietro Bellini2Massimiliano Ugoccioni3Irene Silvestrini3
Anna Ceraso2
Antonio Vita1
Mario Rotondi3,4
Francesco Bertagna1
Carlo Cappelli1*- 1University of Brescia, Brescia, Italy
- 2Spedali Civili Di Brescia, Brescia, Lombardy, Italy
- 3University of Pavia, Pavia, Lombardy, Italy
- 4IRCCS Fondazione Salvatore Maugeri, Pavia, Lombardy, Italy
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction: Thyroid hormones play a crucial role in brain function, yet the relationship between TSH and bipolar disorder remains unclear. This review aims to synthesize the current literature to clarify the interplay between serum TSH levels and both the phenotype and severity of bipolar disorder. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, and Web of Science databases through May 2025. Studies were included based on the PICO framework: What are the TSH levels in first-episode drug-naïve BD patients compared to healthy controls, and do TSH levels differ between manic and depressive phenotypes? The review follows PRISMA guidelines. Study quality and risk of bias were assessed using QUADAS-2. Results: Seventeen studies out of 3,007 were included. Meta-analysis revealed that 1,946 drug-naïve BD patients had lower TSH levels compared to 400 healthy controls (SMD = -0.395 mIU/L, 95% CI: -0.695 to -0.095). Among 830 BD patients, those with a depressive phenotype (n=494) had higher TSH levels than manic patients (SMD = +0.575 mIU/L, 95% CI: -1.074 to -0.075). Discussion: Our data suggest that TSH levels can modulate the onset and severity of psychiatric diseases. Interventional studies targeting TSH modulation, particularly in euthyroid patients, are warranted.
Keywords: thyroid, Thyroid Hormones, Bipolar Disorder, TSH, BD manic, BD depression
Received: 21 Feb 2025; Accepted: 24 Jul 2025.
Copyright: © 2025 Gatta, Maltese, Dondi, Bellini, Ugoccioni, Silvestrini, Ceraso, Vita, Rotondi, Bertagna and Cappelli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Carlo Cappelli, University of Brescia, Brescia, Italy
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.