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Association between thyroid hormone T3 and aggression in drug-naïve schizophrenia: a directed acyclic graph analysis.

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Title: Association between thyroid hormone T3 and aggression in drug-naïve schizophrenia: a directed acyclic graph analysis.
Authors: Yao C; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Jiang C; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Zhang M; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Su Q; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Sun X; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Feng Z; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Zhou B; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Li M; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China., Qiu Y; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China. qiuyuying1987@126.com., Li J; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China. jieli@tmu.edu.cn.
Source: European archives of psychiatry and clinical neuroscience [Eur Arch Psychiatry Clin Neurosci] 2026 Oct; Vol. 276 (7), pp. 3531-3541. Date of Electronic Publication: 2026 Jul 08.
Publication Type: Journal Article
Language: English
Journal Info: Publisher: Springer International Country of Publication: Germany NLM ID: 9103030 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1433-8491 (Electronic) Linking ISSN: 09401334 NLM ISO Abbreviation: Eur Arch Psychiatry Clin Neurosci Subsets: MEDLINE
Imprint Name(s): Original Publication: Berlin ; New York : Springer International, c1990-
MeSH Terms: Schizophrenia*/blood , Schizophrenia*/physiopathology , Triiodothyronine*/blood , Aggression*/physiology , Thyrotropin*/blood , Schizophrenic Psychology*, Thyroxine/blood ; Humans ; Male ; Female ; Adult ; Case-Control Studies ; Middle Aged ; Psychiatric Status Rating Scales ; Young Adult
Abstract: Background: Aggression is a major clinical issue in schizophrenia, but its biological basis remains unclear. This study examined the relationship between thyroid hormones, psychiatric symptoms, and aggression in drug-naïve schizophrenia (DNS) patients using causal inference methods.
Methods: In a case-control study, we examined 161 DNS patients and 63 healthy controls. Aggression was assessed with the Modified Overt Aggression Scale (MOAS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). Serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were measured. DAG modeling, multivariable regression, mediation, and sensitivity analyses were conducted to characterize the relationships among thyroid hormones, psychiatric symptoms, and aggression.
Results: DNS patients exhibited significantly lower TSH levels than controls (t = - 24.81, p < 0.001). Within the schizophrenia cohort, the high-aggression group showed higher T3 levels (t = 2.24, p = 0.03) and more severe positive symptoms (t = 2.85, p < 0.001) than the low-aggression group. DAG analysis identified a direct association between T3 and aggression severity. In multivariable regression analyses, T3 remained significantly associated with aggression severity after adjustment for T4, age, and sex (β = 5.08, p = 0.01); and the association remained significant after further adjustment for positive and negative symptom dimensions (β = 4.99, p = 0.01). Mediation analyses found no evidence that positive or negative symptom dimensions explained this association. Sensitivity analyses supported the robustness of the findings.
Conclusions: Higher T3 levels were associated with greater aggression severity in patients with schizophrenia.
(© 2026. Springer-Verlag GmbH Germany, part of Springer Nature.)
Competing Interests: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: The design, data collection, analysis and interpretation of the results of this study were based solely on scientific principles and ethical standards. All authors contributed their expertise to all stages of the study and approved the final manuscript.
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J Comput Biol. 2000;7(3-4):601-20. (PMID: 11108481)
Epidemiology. 1999 Jan;10(1):37-48. (PMID: 9888278)
Asian J Psychiatr. 2020 Jan;47:101846. (PMID: 31715468)
PLoS One. 2023 Jun 14;18(6):e0287037. (PMID: 37314996)
Exp Ther Med. 2020 Oct;20(4):3483-3487. (PMID: 32905000)
Int J Methods Psychiatr Res. 2019 Sep;28(3):e1776. (PMID: 30810262)
J Nerv Ment Dis. 1988 Sep;176(9):539-46. (PMID: 3418327)
Int J Epidemiol. 2016 Dec 1;45(6):1887-1894. (PMID: 28089956)
Int J Psychiatry Clin Pract. 2009;13(4):303-6. (PMID: 24916941)
Vitam Horm. 2018;106:313-331. (PMID: 29407440)
J Endocr Soc. 2022 Jan 06;6(2):bvab194. (PMID: 35059548)
Br J Psychiatry. 2025 Feb;226(2):100-107. (PMID: 40091674)
J Prev Med Public Health. 2021 May;54(3):166-172. (PMID: 34092062)
Annu Rev Psychol. 2002;53:27-51. (PMID: 11752478)
Psychol Rev. 1997 Oct;104(4):667-85. (PMID: 9337628)
Eur J Epidemiol. 2019 Mar;34(3):211-219. (PMID: 30840181)
Psychoneuroendocrinology. 2024 Sep;167:107087. (PMID: 38820716)
Int J Epidemiol. 2021 May 17;50(2):620-632. (PMID: 33330936)
Schizophr Res. 2012 May;137(1-3):246-50. (PMID: 22356801)
Psychiatry Res. 2015 Jun 30;227(2-3):253-7. (PMID: 25858801)
Ann Gen Psychiatry. 2020 Jun 03;19:36. (PMID: 32518577)
Schizophr Bull. 1987;13(2):261-76. (PMID: 3616518)
Noro Psikiyatr Ars. 2016 Jun;53(2):120-125. (PMID: 28360783)
Eur J Epidemiol. 2023 Oct;38(10):1081-1088. (PMID: 37589836)
Int J Offender Ther Comp Criminol. 2024 May 6;:306624X241248356. (PMID: 38708899)
CNS Spectr. 2015 Jun;20(3):254-79. (PMID: 25936249)
Maturitas. 2015 Jun;81(2):266-75. (PMID: 25896972)
Neuropsychiatr Dis Treat. 2024 Nov 18;20:2169-2175. (PMID: 39583013)
Thyroid. 2023 Sep;33(9):1013-1028. (PMID: 37655789)
J Neuroendocrinol. 2021 Mar;33(3):e12948. (PMID: 33655583)
Grant Information: TJWJ2023MS039 Tianjin Health Research Project; TJYXZDXK-3-015B Tianjin Key Medical Discipline Construction Project; 22JCZDJC00110 Natural Science Foundation of Tianjin Municipal Science and Technology Bureau
Contributed Indexing: Keywords: Aggression; Directed acyclic graphs; Drug-naïve schizophrenia
Substance Nomenclature: 06LU7C9H1V (Triiodothyronine)
Q51BO43MG4 (Thyroxine)
9002-71-5 (Thyrotropin)
Entry Date(s): Date Created: 20260708 Date Completed: 20260910 Latest Revision: 20261008
Update Code: 20261008
DOI: 10.1007/s00406-026-02312-z
PMID: 42420552
Database: MEDLINE
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  Data: Association between thyroid hormone T3 and aggression in drug-na&#239;ve schizophrenia: a directed acyclic graph analysis.
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  Data: &lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Yao+C%22&quot;&gt;Yao C&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Jiang+C%22&quot;&gt;Jiang C&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhang+M%22&quot;&gt;Zhang M&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Su+Q%22&quot;&gt;Su Q&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Sun+X%22&quot;&gt;Sun X&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Feng+Z%22&quot;&gt;Feng Z&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Zhou+B%22&quot;&gt;Zhou B&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+M%22&quot;&gt;Li M&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Qiu+Y%22&quot;&gt;Qiu Y&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China. qiuyuying1987@126.com.&lt;br /&gt;&lt;searchLink fieldCode=&quot;AU&quot; term=&quot;%22Li+J%22&quot;&gt;Li J&lt;/searchLink&gt;; Tianjin Anding Hospital, Mental Health Center, Tianjin Medical University, 13 Liulin Road, Hexi District, Tianjin, 300222, China. jieli@tmu.edu.cn.
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  Data: &lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Schizophrenia%22&quot;&gt;Schizophrenia*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Schizophrenia+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Schizophrenia%22&quot;&gt;Schizophrenia*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Schizophrenia+physiopathology%22&quot;&gt;physiopathology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Triiodothyronine%22&quot;&gt;Triiodothyronine*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Triiodothyronine+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Aggression%22&quot;&gt;Aggression*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Aggression+physiology%22&quot;&gt;physiology&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Thyrotropin%22&quot;&gt;Thyrotropin*&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Thyrotropin+blood%22&quot;&gt;blood&lt;/searchLink&gt; &lt;br /&gt;&lt;searchLink fieldCode=&quot;MM&quot; term=&quot;%22Schizophrenic+Psychology%22&quot;&gt;Schizophrenic Psychology*&lt;/searchLink&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Thyroxine%22&quot;&gt;Thyroxine&lt;/searchLink&gt;/&lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Thyroxine+blood%22&quot;&gt;blood&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Humans%22&quot;&gt;Humans&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Male%22&quot;&gt;Male&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Female%22&quot;&gt;Female&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Adult%22&quot;&gt;Adult&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Case-Control+Studies%22&quot;&gt;Case-Control Studies&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Middle+Aged%22&quot;&gt;Middle Aged&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Psychiatric+Status+Rating+Scales%22&quot;&gt;Psychiatric Status Rating Scales&lt;/searchLink&gt; ; &lt;searchLink fieldCode=&quot;MH&quot; term=&quot;%22Young+Adult%22&quot;&gt;Young Adult&lt;/searchLink&gt;
– Name: Abstract
  Label: Abstract
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  Data: Background: Aggression is a major clinical issue in schizophrenia, but its biological basis remains unclear. This study examined the relationship between thyroid hormones, psychiatric symptoms, and aggression in drug-na&#239;ve schizophrenia (DNS) patients using causal inference methods.&lt;br /&gt;Methods: In a case-control study, we examined 161 DNS patients and 63 healthy controls. Aggression was assessed with the Modified Overt Aggression Scale (MOAS) and psychiatric symptoms with the Positive and Negative Syndrome Scale (PANSS). Serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were measured. DAG modeling, multivariable regression, mediation, and sensitivity analyses were conducted to characterize the relationships among thyroid hormones, psychiatric symptoms, and aggression.&lt;br /&gt;Results: DNS patients exhibited significantly lower TSH levels than controls (t = - 24.81, p &amp;lt; 0.001). Within the schizophrenia cohort, the high-aggression group showed higher T3 levels (t = 2.24, p = 0.03) and more severe positive symptoms (t = 2.85, p &amp;lt; 0.001) than the low-aggression group. DAG analysis identified a direct association between T3 and aggression severity. In multivariable regression analyses, T3 remained significantly associated with aggression severity after adjustment for T4, age, and sex (β = 5.08, p = 0.01); and the association remained significant after further adjustment for positive and negative symptom dimensions (β = 4.99, p = 0.01). Mediation analyses found no evidence that positive or negative symptom dimensions explained this association. Sensitivity analyses supported the robustness of the findings.&lt;br /&gt;Conclusions: Higher T3 levels were associated with greater aggression severity in patients with schizophrenia.&lt;br /&gt; (&#169; 2026. Springer-Verlag GmbH Germany, part of Springer Nature.)
– Name: Abstract
  Label: Competing Interests
  Group: Ab
  Data: Declarations. Conflict of interest: The authors declare that they have no competing interests. Ethical approval: The design, data collection, analysis and interpretation of the results of this study were based solely on scientific principles and ethical standards. All authors contributed their expertise to all stages of the study and approved the final manuscript.
– Name: Ref
  Label: References
  Group: RefInfo
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  Data: TJWJ2023MS039 Tianjin Health Research Project; TJYXZDXK-3-015B Tianjin Key Medical Discipline Construction Project; 22JCZDJC00110 Natural Science Foundation of Tianjin Municipal Science and Technology Bureau
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  Data: &lt;i&gt;Keywords: &lt;/i&gt;Aggression; Directed acyclic graphs; Drug-na&#239;ve schizophrenia
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  Label: Entry Date(s)
  Group: Date
  Data: &lt;i&gt;Date Created: &lt;/i&gt;20260708 &lt;i&gt;Date Completed: &lt;/i&gt;20260910 &lt;i&gt;Latest Revision: &lt;/i&gt;20261008
– Name: DateUpdate
  Label: Update Code
  Group: Date
  Data: 20261008
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s00406-026-02312-z
– Name: AN
  Label: PMID
  Group: ID
  Data: 42420552
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=cmedm&AN=42420552
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.1007/s00406-026-02312-z
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        StartPage: 3531
    Subjects:
      – SubjectFull: Thyroxine blood
        Type: general
      – SubjectFull: Humans
        Type: general
      – SubjectFull: Male
        Type: general
      – SubjectFull: Female
        Type: general
      – SubjectFull: Adult
        Type: general
      – SubjectFull: Case-Control Studies
        Type: general
      – SubjectFull: Middle Aged
        Type: general
      – SubjectFull: Psychiatric Status Rating Scales
        Type: general
      – SubjectFull: Young Adult
        Type: general
      – SubjectFull: Schizophrenia blood
        Type: general
      – SubjectFull: Schizophrenia physiopathology
        Type: general
      – SubjectFull: Triiodothyronine blood
        Type: general
      – SubjectFull: Aggression physiology
        Type: general
      – SubjectFull: Thyrotropin blood
        Type: general
      – SubjectFull: Schizophrenic Psychology
        Type: general
    Titles:
      – TitleFull: Association between thyroid hormone T3 and aggression in drug-naïve schizophrenia: a directed acyclic graph analysis.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Yao C
      – PersonEntity:
          Name:
            NameFull: Jiang C
      – PersonEntity:
          Name:
            NameFull: Zhang M
      – PersonEntity:
          Name:
            NameFull: Su Q
      – PersonEntity:
          Name:
            NameFull: Sun X
      – PersonEntity:
          Name:
            NameFull: Feng Z
      – PersonEntity:
          Name:
            NameFull: Zhou B
      – PersonEntity:
          Name:
            NameFull: Li M
      – PersonEntity:
          Name:
            NameFull: Qiu Y
      – PersonEntity:
          Name:
            NameFull: Li J
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 10
              Text: 2026 Oct
              Type: published
              Y: 2026
          Identifiers:
            – Type: issn-electronic
              Value: 1433-8491
          Numbering:
            – Type: volume
              Value: 276
            – Type: issue
              Value: 7
          Titles:
            – TitleFull: European archives of psychiatry and clinical neuroscience
              Type: main
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