Abstract

Thyroid hormones play an important role in brain development, and thyroid hormone insufficiency during the perinatal period results in severe developmental delays. Perinatal thyroid hormone deficiency is clinically known as congenital hypothyroidism, which is caused by dysgenesis of the thyroid gland or low iodine intake. If the disorder is not diagnosed or not treated early, the neuronal architecture is perturbed by thyroid hormone insufficiency, and neuropathological findings, such as abnormal synapse formation, defects in neuronal migration, and impairment of myelination, are observed in the brains of such patients. Furthermore, the expression of psychiatric disorder-related molecules, especially parvalbumin, is significantly decreased by thyroid hormone insufficiency during the perinatal period. Animal experiments using hypothyroidism models display decreased parvalbumin expression and abnormal brain architecture, and these experimental results show reproducibility and stability. These basic studies reinforce the results of epidemiological studies, suggesting the relevance of thyroid dysfunction in psychiatric disorders. In this review, we discuss the disruption of brain function associated with congenital hypothyroidism from the perspective of basic and clinical research.

Highlights

  • Thyroid hormones are synthesized in and released by the thyroid gland, with thyroxine (T4) comprising the highest concentration of these hormones

  • There is not a clear explanation regarding the behavior of methyl CpG binding protein 2 (MeCP2) transcripts and translated products differs between organs, these results suggest that thyroid hormones have a significant effect on the expression of MeCP2, at least, and the relationship between thyroid function and MeCP2 might be that of reciprocal interactions rather than one-way interactions (Table 4)

  • We discussed the effects of thyroid hormones on the neural architecture of the brain, and concisely mentioned their relationship with parvalbumin and/or MeCP2

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Summary

Introduction

Thyroid hormones are synthesized in and released by the thyroid gland, with thyroxine (T4) comprising the highest concentration of these hormones. Thyroid hormones during the perinatal period are important for normal development of the brain, and congenital hypothyroidism causes serious developmental delay if proper treatment is not implemented immediately after birth in such patients (Morreale de Escobar et al, 1987; Rastogi and LaFranchi, 2010). A typical neuropathological finding caused by thyroid hormone insufficiency is a decrease in the parvalbumin of GABAergic neurons.

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