Effects of Thyroid Status on Regional Brain Volumes: A Diagnostic and Genetic Imaging Study in UK Biobank

Abstract

Background Thyroid hormone is essential for optimal human neurodevelopment and may modify the risk of attention-deficit hyperactivity disorder (ADHD). However, the brain structures involved are unknown and it is unclear if the adult brain is also susceptible to changes in thyroid status. Methods We used international classification of disease-10 codes, polygenic thyroid scores at different thresholds of association with thyroid traits (pT-values) and image-derived phenotypes in UK Biobank (n=18,825) to investigate the effects of a recorded diagnosis of thyroid disease and genetic risk for thyroid status on cerebellar and subcortical grey matter volume. Regional genetic pleiotropy between thyroid status and ADHD was explored using the GWAS-pairwise method. Results A recorded diagnosis of hypothyroidism (n=419) was associated with significant reductions in total cerebellar and pallidum grey matter volumes (β[95%CI] = -0.14[-0.23, -0.06], p = 0.0005 and β[95%CI] = -0.12[-0.20, -0.04], p = 0.0042, respectively), mediated in part by increases in Body Mass Index. Whilst we found no evidence for total cerebellar volume alterations with increased polygenic scores for any thyroid trait, opposing influences of increased polygenic scores for hypo- and hyperthyroidism were found in the pallidum (pT<1e-3: β[95%CI] = -0.02[-0.03,-0.01], p = 0.0003 and pT<1e-7: β[95%CI] = 0.02[0.01,0.03], p = 0.0003, respectively). Neither hypo- nor hyperthyroidism showed evidence of regional genetic pleiotropy with ADHD. Conclusions Thyroid status affects grey matter volume in adults, particularly at the level of the cerebellum and pallidum, with potential implications for the regulation of motor, cognitive and affective function.

Impaired sensitivity to thyroid hormones and carotid plaque in patients with coronary heart disease: A RCSCD-TCM study in China

“…Rheumatological diseases included rheumatoid arthritis (ICD-10 codes M05-06), psoriatic arthritis (ICD-10 codes L40), ankylosing spondylitis (ICD-10 codes M45), vasculitis (ICD-10 codes I77), systemic lupus erythematosus (ICD-10 codes M32), sjögren (ICD-10 codes M35), poly/dermatomyositis (ICD-10 codes M33), systemic sclerosis (ICD-10 codes M34) ( 20 , 21 ). Thyroid diseases (ICD-10 codes E00-E07) included hyperthyroidism, hypothyroidism, thyroiditis, thyroid cyst, thyrophyma, or thyroid nodule ( 22 ). Autoimmune thyroid diseases (AITD) included Graves’ disease and Hashimoto thyroiditis ( 23 , 24 ).…”

“…CHD, coronary heart disease; TSH, thyroid stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine. Thyroid diseases (ICD-10 codes E00-E07) included hyperthyroidism, hypothyroidism, thyroiditis, thyroid cyst, thyrophyma, or thyroid nodule (22). Autoimmune thyroid diseases (AITD) included Graves' disease and Hashimoto thyroiditis (23,24).…”

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder

“…A recent prospective cohort study found that maternal THs concentrations during pregnancy were associated with lower gray matter volumes, which indicated that THs affect brain development (55). A large UK Biobank study also provided evidence for the effect of THs on gray matter volumes in adults, which extends our understanding of the effect of THs on the neuronal structure in the human brain (56). In our study, serum TSH levels were decreased and positively associated with gray matter volume in the right MFG in MDD patients.…”

Gray matter reduction is associated with cognitive dysfunction in depressed patients comorbid with subclinical hypothyroidism

“…It is widely recognized that THs are essential for both the development and maturation of the cerebrum and affect such diverse events as neuronal integration and processing, myelination, and glial cell proliferation. A large United Kingdom Biobank study demonstrated that thyroid status could affect adult GMV ( Chambers et al, 2021 ). Another recent study showed that low maternal thyroid function during pregnancy is associated with minor child gray matter ( Jansen et al, 2019 ).…”