Thyroid Disease and Mental Disorders: Cause and Effect or Only comorbidity?

Robertas Bunevičius; Arthur J. Prange Jr


Curr Opin Psychiatry. 2010;23(4):363-368. 

In This Article


Hypothyroidism is frequently accompanied by diminished cognition, slow thought process, slow motor function, and drowsiness. Myxedema is associated with severe mental disorders including psychoses, sometimes called 'myxematous madness'. Depression is especially related to hypothyroidism; even subclinical hypothyroidism may affect mood.[23] Thyroid deficits are frequently observed in bipolar patients, especially in women with the rapid cycling form of the disease.[24] Both subclinical hypothyroidism and subclinical hyperthyroidism increase the risk for Alzheimer's disease, especially in women.[25] However, most hypothyroid patients do not meet the criteria for a mental disorder.

A recent study evaluated brain glucose metabolism during T4 treatment of hypothyroidism. A reduction in depression and cognitive symptoms was associated with restoration of metabolic activity in brain areas that are integral to the regulation of mood and cognition.[26••]

In hypothyroidism, replacement therapy with T4 remains the treatment of choice and resolves most physical and psychological signs and symptoms in most patients. However, some patients do not feel entirely well despite doses of T4 that are usually adequate.[27] In T4-treated patients, it was found that reduced psychological well being is associated with occurrence of polymorphism in the D2 gene,[28••] as well as in the OATP1c1 gene.[29]

Thyroid hormone replacement with a combination of T4 and T3, in comparison with T4 monotherapy, improves mental functioning in some but not all hypothyroid patients,[30,31•] and most of the patients subjectively prefer combined treatment.[32] Two studies have evaluated whether D2 polymorphism is associated with changes in psychological well being after combined T4 and T3 treatment. One underpowered study[33] reported a trend toward improvement. In a second study[28••] involving a very large sample, D2 polymorphism was associated with improvement in psychological well being after T4 and T3 treatment. In a recent review, it was concluded that future trials on thyroid hormone replacement should target genetic polymorphisms in deiodinase and thyroid hormone transporters.[34]


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