Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis

IntroductionThyroid 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.M...

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Main Authors: Elisa Gatta, Virginia Maltese, Francesco Dondi, Pietro Bellini, Massimiliano Ugoccioni, Irene Silvestrini, Anna Ceraso, Antonio Vita, Mario Rotondi, Francesco Bertagna, Carlo Cappelli
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1580854/full
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author Elisa Gatta
Elisa Gatta
Virginia Maltese
Francesco Dondi
Pietro Bellini
Massimiliano Ugoccioni
Irene Silvestrini
Anna Ceraso
Anna Ceraso
Antonio Vita
Antonio Vita
Mario Rotondi
Mario Rotondi
Francesco Bertagna
Francesco Bertagna
Carlo Cappelli
Carlo Cappelli
author_facet Elisa Gatta
Elisa Gatta
Virginia Maltese
Francesco Dondi
Pietro Bellini
Massimiliano Ugoccioni
Irene Silvestrini
Anna Ceraso
Anna Ceraso
Antonio Vita
Antonio Vita
Mario Rotondi
Mario Rotondi
Francesco Bertagna
Francesco Bertagna
Carlo Cappelli
Carlo Cappelli
author_sort Elisa Gatta
collection DOAJ
description IntroductionThyroid 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.MethodsA 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.ResultsSeventeen 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).DiscussionOur 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.
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spelling doaj-art-a94873132a934b71a64c863d16b4bdd22025-08-20T03:36:54ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-08-011610.3389/fendo.2025.15808541580854Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysisElisa Gatta0Elisa Gatta1Virginia Maltese2Francesco Dondi3Pietro Bellini4Massimiliano Ugoccioni5Irene Silvestrini6Anna Ceraso7Anna Ceraso8Antonio Vita9Antonio Vita10Mario Rotondi11Mario Rotondi12Francesco Bertagna13Francesco Bertagna14Carlo Cappelli15Carlo Cappelli16Department of Clinical and Experimental Sciences, SSD Endocrinologia, University of Brescia, ASST Spedali Civili, Brescia, ItalyCentro per la Diagnosi e Cura delle Neoplasie Endocrine e delle Malattie della Tiroide, University of Brescia, Brescia, ItalyDepartment of Clinical and Experimental Sciences, SSD Endocrinologia, University of Brescia, ASST Spedali Civili, Brescia, ItalyNuclear Medicine, University of Brescia, ASST Spedali Civili, Brescia, ItalyNuclear Medicine, University of Brescia, ASST Spedali Civili, Brescia, ItalyDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, ItalyDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili, Brescia, ItalyDepartment of Mental Health and Addiction Services, University of Brescia, ASST Spedali Civili, Brescia, ItalyDepartment of Clinical and Experimental Sciences, University of Brescia, ASST Spedali Civili, Brescia, ItalyDepartment of Mental Health and Addiction Services, University of Brescia, ASST Spedali Civili, Brescia, ItalyDepartment of Internal Medicine and Therapeutics, University of Pavia, Pavia, ItalyLaboratory for Endocrine Disruptors, Unit of Endocrinology and Metabolism, Istituti Clinici Scientifici Maugeri IRCCS, Pavia, ItalyCentro per la Diagnosi e Cura delle Neoplasie Endocrine e delle Malattie della Tiroide, University of Brescia, Brescia, ItalyNuclear Medicine, University of Brescia, ASST Spedali Civili, Brescia, ItalyDepartment of Clinical and Experimental Sciences, SSD Endocrinologia, University of Brescia, ASST Spedali Civili, Brescia, ItalyCentro per la Diagnosi e Cura delle Neoplasie Endocrine e delle Malattie della Tiroide, University of Brescia, Brescia, ItalyIntroductionThyroid 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.MethodsA 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.ResultsSeventeen 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).DiscussionOur 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1580854/fullthyroidthyroid hormonesbipolar disorderTSHBD manicBD depression
spellingShingle Elisa Gatta
Elisa Gatta
Virginia Maltese
Francesco Dondi
Pietro Bellini
Massimiliano Ugoccioni
Irene Silvestrini
Anna Ceraso
Anna Ceraso
Antonio Vita
Antonio Vita
Mario Rotondi
Mario Rotondi
Francesco Bertagna
Francesco Bertagna
Carlo Cappelli
Carlo Cappelli
Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis
Frontiers in Endocrinology
thyroid
thyroid hormones
bipolar disorder
TSH
BD manic
BD depression
title Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis
title_full Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis
title_fullStr Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis
title_full_unstemmed Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis
title_short Thyrotropin levels in first-episode bipolar disorder and their association with clinical phenotypes: systematic review and meta-analysis
title_sort thyrotropin levels in first episode bipolar disorder and their association with clinical phenotypes systematic review and meta analysis
topic thyroid
thyroid hormones
bipolar disorder
TSH
BD manic
BD depression
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1580854/full
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