Neuropsychiatric aspects of hypothyroidism and treatment reversibility. .

Thyroid hormone has important actions in the adult brain, and it is well accepted that hypothyroidism is associated with neuropsychiatric complaints and symptoms. Neuropsychiatric symptoms refer to a spectrum of emotional and cognitive problems that are directly related to changes in the brain secondary to multiple factors, including the direct effects of thyroid disease, as well as hormone deprivation in brain tissue. Hypothyroidism impacts aspects of cognitive functioning and mood. More severe hypothyroidism can mimic melancholic de-pression and dementia. Neuropsychiatric symptoms tend to improve with treatment and normalization to a euthyroid state, though the pattern is inconsistent and complete recovery is uncertain. The degree to which mild hypothyroidism, or subclinical hypothyroidism (SCH), impacts mood and cognitive functions and whether these symptoms respond to treatment, remains controversial. Most studies support a relationship between thyroid state and cognition, particularly slowed information processing speed, reduced efficiency in executive functions, and poor learning. Furthermore, hypo-thyroidism is associated with an increased susceptibility to depression and reductions in health-related quality of life. Controlled studies suggest that cognitive and mood symptoms improve with treatment, though the data are equivocal and limited by diverse methodologies. Functional neuroimaging data provide support for the mood and cognitive findings and treatment reversibility for both overt and SCH. These findings are not, however, without controversy. Recent investigations into the impact of SCH on cognition and mood, coupled epidemiological studies investigating the normal spectrum of thyroid stimulating hormone, have fueled significant debate regarding the appropriate, healthy range for TSH levels. This has led to concern over whether patients with overt hypothyroidism may be undertreated and whether SCH patients are truly out of the range of normal thyroid functioning and should be treated. The following is a review of the extant literature on the impact of hypothyroidism on cognition and mood, reversibility of symptoms, and treatment approaches. The spectrum of thyroid disease is reviewed, but mild, or subclinical, hypothyroidism is emphasized. The potential role of autoimmunity in neuropsychiatric symptoms and treatment resistance is addressed. Limitations of the current literature and future directions are discussed.