Thyroid, Brain and Mood Modulation in Affective Disorder: Insights from Molecular Research and Functional Brain Imaging

Abstract

The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

Hypothyroidism and mood disorders: integrating novel insights from brain imaging techniques

“…Genomic actions of T 3 are mediated through the control and usually increase of gene expression [12,21,22]. Genes that are regulated by thyroid hormones are known to encode for proteins such as myelin, neurotrophins, and proteins that are involved in intracellular signaling pathways [23]. …”

Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder

“…Thyroid hormones modify expression of genes encoding myelin, neurotrophins, and proteins involved in intracellular signaling pathways [7]. They have also neroprotective and vasodilatory effects [8].…”

Interrelation between Thyroid Hormones, Catecholamines, Neuroticism and Physical Aggression in Men with High and Middle Neuroticism Levels

“…In total group of participants moderate positive correlations between neuroticism and T 4 (r=+0.49, p=0.029), between neuroticism and T 3 (r=+0.44, p=0.0506), negative correlation between T 4 and norepinephrine (r=-0.38, p=0.032) were revealed.…”

“…Monoaminergic brain systems have a great influence on the emotions and behavior [1], including aggression [2,3], in humans and animals. The thyroid system influences neurotransmitters (particularly serotonin and norepinephrine) [4]. Free T 3 level in the criminal Antisocial Personality Disorder (APD) group is found to be significantly higher than that in the noncriminal APD group, but in the criminal APD group, there is no significant correlation between thyroid hormone levels and aggression [5].…”