Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

Marilu Jurado-Flores; Firas Warda; Arshag Mooradian

Disclosures

J Endo Soc. 2022;6(2) 

In This Article

Abstract and Introduction

Abstract

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system during embryogenesis and early infancy. However, the TH-responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems. Cognitive decline, dysphoria, and depression are common manifestations of overt hypothyroidism while hyperthyroidism can cause agitation, acute psychosis, and apathy, especially in older people. Whereas levothyroxine treatment can reverse dementia in the setting of hypothyroidism, the effect of levothyroxine on depressive symptoms in subjects with subclinical hypothyroidism is controversial. The use of supraphysiologic doses of TH to treat depression refractory to antidepressant remains a viable therapeutic tool with the caveat that excessive doses of thyroid hormone to treat depression may have potentially damaging effects on other organ systems. The present communication describes the pathophysiology of neuropsychiatric manifestations of thyroid disease, including changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier dysfunction, increased risk of cerebrovascular disease, and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease. Elucidating the molecular mechanisms of TH effect on cerebral tissue will help identify novel therapeutic targets for managing people with neuropsychiatric disorders.

Introduction

Thyroid hormones (TH) have a cardinal role in the development of the central nervous system (CNS) during embryogenesis and early infancy.[1] During these early stages of life, a number of genes show robust changes in response to TH.[1] However, those TH-responsive genes in the developing brain cease to respond to TH in adulthood. Nevertheless, thyroid dysfunction in adults is commonly associated with a host of cognitive and psychiatric problems.[2–6] The pathophysiology of the TH-related changes in the cerebral tissue is diverse and includes changes in neurotransmission, alterations in neuronal or glial cell gene expression, blood-brain barrier (BBB) dysfunction, increased risk of cerebrovascular disease, and occasionally cerebral inflammatory disease in the context of autoimmune thyroid disease (Figure 1).

Figure 1.

Thyroid hormone effects on cerebral tissue.

The aim of this communication is to review the cognitive and psychiatric changes observed in people with thyroid dysfunction and to describe the biochemical and physiological changes that occur in the cerebral tissue in response to TH.

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