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Causal link between thyroid function and schizophrenia: a two-sample Mendelian randomization study.

Dennis Freuer1, Christa Meisinger2

  • 1Epidemiology, Medical Faculty, University of Augsburg, Augsburg, Germany. dennis.freuer@med.uni-augsburg.de.

European Journal of Epidemiology
|August 17, 2023
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Summary
This summary is machine-generated.

Genetic liability for hypothyroidism, characterized by elevated thyroid-stimulating hormone (TSH), was inversely associated with schizophrenia risk. This suggests higher TSH levels may reduce the likelihood of developing schizophrenia.

Keywords:
Free thyroxineHyperthyroidismHypothyroidismMendelian randomizationSchizophreniaThyroid functionThyroid-stimulating hormone

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Area of Science:

  • Psychiatry
  • Endocrinology
  • Genetics

Background:

  • Schizophrenia is a complex psychiatric disorder with significant societal impact.
  • Altered thyroid function is observed in individuals with schizophrenia, but existing research presents conflicting results.
  • The causal relationship between thyroid function and schizophrenia remains unclear.

Purpose of the Study:

  • To investigate the potential causal relationship between thyroid function and schizophrenia using a bidirectional Mendelian randomization study.
  • To determine if thyroid function influences schizophrenia risk or vice versa.

Main Methods:

  • A bidirectional two-sample Mendelian randomization (MR) study was performed using genome-wide association study (GWAS) summary statistics from up to 330,132 Europeans.
  • Thyroid function was assessed by normal-range thyroid-stimulating hormone (TSH), free thyroxine levels, and TSH status (increased/decreased).
  • The primary analysis employed the iterative radial inverse-variance weighted approach, with robustness checks using pleiotropy-robust methods and network analysis.

Main Results:

  • Genetic liability for hypothyroidism (elevated TSH) showed a significant inverse association with schizophrenia risk ([Formula: see text]; 95% CI: -0.10 to -0.02).
  • No significant associations were found between other thyroid parameters (free thyroxine, decreased TSH) and schizophrenia.
  • No evidence of a causal effect of schizophrenia on thyroid function was detected in the reverse direction.

Conclusions:

  • Elevated thyroid-stimulating hormone (TSH) levels are associated with a reduced risk of schizophrenia.
  • Thyroid function, particularly TSH regulation, may play a role in the pathophysiology of schizophrenia.
  • Further research into the hypothalamic-pituitary-thyroid axis in schizophrenia development is warranted.