Pathophysiology and Clinical Features of Neuropsychiatric Manifestations of Thyroid Disease

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.

Automated summary

Thyroid hormones play a crucial role in the development of the central nervous system during embryogenesis and early infancy. However, the developing brain stops responding to thyroid hormones in adulthood. Nevertheless, thyroid dysfunction in adults is often associated with cognitive and psychiatric problems. Overt hypothyroidism can cause cognitive decline, dysphoria, and depression, while hyperthyroidism can lead to agitation, acute psychosis, and apathy. The use of levothyroxine to treat dementia in hypothyroidism is effective, but its effect on depressive symptoms in subclinical hypothyroidism is controversial.