Abstract
Thyroid hormones play a critical role in brain development but also in the adult human brain by modulating metabolic activity. Hypothyroid states are associated with both functional and structural brain alterations also seen in patients with major depression. Recent animal experimental and preclinical data indicate subtle changes in myelination, microvascular density, local neurogenesis, and functional networks. The translational validity of such studies is obviously limited. Clinical evidence for neurobiological correlates of different stages and severities of hypothyroidism and effects of pharmacological intervention is lacking but may be achieved using advanced imaging techniques, e.g. functional and quantitative MRI techniques applied to patients with hypothyroidism before and after hormone replacement therapy.
Highlights
The profound influence of thyroid hormones on brain development in humans has been studied extensively [1,2,3,4,5,6]
In the first double-blind randomized placebo-controlled trial (RCT) to evaluate efficacy and tolerability of supraphysiological doses of L-T4 in 63 patients, we found that bipolar depressed women treated with L-T4 showed a better improvement in depression scores than those treated with placebo
Structural changes related to myelin can be studied with quantitative T2 or quantitative magnetization transfer (MT) imaging [54]
Summary
The profound influence of thyroid hormones on brain development in humans has been studied extensively [1,2,3,4,5,6]. Circulating TSH levels before initiation of therapy showed a significant positive correlation with glucose metabolism in the right ACC and negative correlations in the hippocampus These two regions express TSH receptors very densely according to topographic studies in rat and human [70], whereby suggesting a direct and relevant effect of elevated TSH levels on the limbic system is highly speculative. Despite clinical evidence of an increased vulnerability for affective disorders coming along with hypothyroid states, neurobiological correlates of this disposition are not systematically investigated yet This is of particular interest because a study by Maheu et al [81] demonstrated that fMRI could detect greater hippocampal and amygdala activation in 12 non-depressed adolescent patients with Cushing’s syndrome, when encoding affective stimuli (i.e. emotional faces) compared to 22 healthy controls. CushingÂs syndrome is defined by hypercortisolemia and highly associated with prevalence of depressive symptoms in adults [83] and shows in this respect distinct parallels to hypothyroidism
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