How Thyroid Hormones Influence Metabolism, Mood, and the Brain

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Thyroid hormones are chemical messengers produced by the thyroid gland that circulate through the bloodstream and influence cells throughout the body. Their primary role is the regulation of metabolism, but thyroid hormones also affect brain function, mood, cognition, and behavior.

The Brain–Pituitary–Thyroid Axis

Thyroid function is regulated through a three-step hormonal system known as the hypothalamic-pituitary-thyroid (HPT) axis.

The hypothalamus, located in the brain, releases thyrotropin-releasing hormone (TRH). TRH stimulates the pituitary gland to release thyroid-stimulating hormone (TSH). TSH then stimulates the thyroid gland in the neck to produce thyroid hormones, primarily T4 (thyroxine). T4 is subsequently converted into the more biologically active hormone T3 (triiodothyronine).

This regulatory system allows the brain to influence how much thyroid hormone circulates throughout the body.

Thyroid Hormones and Metabolism

One of the major functions of thyroid hormones is to regulate metabolic activity.

Metabolism refers broadly to the chemical processes through which the body produces, uses, stores, and breaks down substances and energy. It consists of two general types of processes:

  • Anabolism: the construction of molecules and tissues.
  • Catabolism: the breakdown of molecules and tissues.

Together, anabolic and catabolic processes constitute metabolism.

Thyroid hormones generally increase metabolic activity. When thyroid hormone levels rise, many physiological processes occur more rapidly. Cells consume more energy, cardiovascular activity increases, and heat production rises.

One mechanism through which thyroid hormones influence cellular activity involves sodium-potassium ATPase, an enzyme found in cell membranes throughout the body. This enzyme moves sodium and potassium ions across cell membranes and contributes to cellular electrical activity. Thyroid hormones can increase the activity and expression of these ion-transport systems, contributing to increased metabolic activity.

Thyroid hormones also have important cardiovascular effects. They can increase heart rate, cardiac activity, and the responsiveness of the cardiovascular system to sympathetic stimulation.

Hypothyroidism

Hypothyroidism occurs when the body does not have sufficient thyroid hormone.

One common cause is Hashimoto’s thyroiditis, an autoimmune disease in which the immune system targets thyroid tissue. Over time, this can damage the thyroid gland and reduce its ability to produce thyroid hormones.

Reduced thyroid hormone levels slow many physiological processes. Common effects can include fatigue, reduced energy, weight gain, sensitivity to cold, slower heart rate, and cognitive difficulties.

Thinking and memory may also become slower or less efficient.

Hyperthyroidism

Hyperthyroidism occurs when thyroid hormone activity is excessive.

One important cause is Graves’ disease, an autoimmune disorder in which antibodies stimulate the thyroid gland, causing excessive production of thyroid hormones.

The physiological effects are generally opposite to those associated with hypothyroidism. Hyperthyroidism can produce weight loss, increased heart rate, heat intolerance, increased metabolic activity, restlessness, and increased physiological arousal.

Graves’ disease can also produce characteristic eye symptoms, including protrusion of the eyes, known as exophthalmos or proptosis.

Hyperthyroidism can arise from causes other than Graves’ disease, just as hypothyroidism can have causes other than Hashimoto’s thyroiditis.

Thyroid Hormones and the Brain

Although thyroid hormones are strongly associated with metabolism, they also influence the nervous system.

Hypothyroidism can be associated with slower cognition, memory difficulties, fatigue, and depressive symptoms. In some individuals, an underlying thyroid disorder may contribute substantially to psychiatric symptoms.

One feature that can occur with severe hypothyroidism and depression is psychomotor slowing, in which thinking, movement, and initiating activities become more difficult or require greater effort.

This relationship illustrates why thyroid function may be evaluated when a person presents with certain depressive or cognitive symptoms.

At the opposite end of the spectrum, excessive thyroid hormone activity can be associated with increased psychological and physiological arousal. Hyperthyroidism may produce anxiety, agitation, restlessness, irritability, sleep disturbance, and emotional instability. In severe cases, it can contribute to manic-like or other significant psychiatric symptoms.

Thus, thyroid hormone levels can influence not only physical metabolism but also emotional and cognitive functioning.

Thyroid Hormones and Neurotransmitters

Thyroid hormones interact with several neurotransmitter systems, including serotonin, dopamine, and norepinephrine. These interactions provide possible mechanisms through which thyroid function can influence mood, alertness, motivation, and behavior.

One brain region of particular interest is the locus coeruleus.

The locus coeruleus is a small structure in the brainstem and a major source of the neurotransmitter norepinephrine in the brain. Its neurons project widely to other brain regions.

Norepinephrine contributes to alertness, attention, arousal, vigilance, and responses to potentially important or threatening events.

Thyroid Hormones, Norepinephrine, and Arousal

Thyroid hormones can interact with the adrenergic system—the system involving adrenaline and norepinephrine.

Adrenaline is also called epinephrine, while noradrenaline is also called norepinephrine. Epinephrine primarily acts as a circulating hormone in the body, whereas norepinephrine has an important role as a neurotransmitter in the brain.

Thyroid hormones can increase the body's responsiveness to adrenergic stimulation. This helps explain some features of hyperthyroidism, such as increased heart rate, heightened physiological arousal, tremor, and sensitivity to stimulation.

Within the brain, thyroid hormones can also influence norepinephrine-related signaling, including activity associated with the locus coeruleus.

Reduced thyroid activity may therefore contribute to reduced arousal, fatigue, cognitive slowing, and depressive symptoms. Excessive thyroid activity may shift the nervous system in the opposite direction, toward greater arousal and responsiveness.

Behavioral and Emotional Effects

The relationship between thyroid function and behavior can therefore be understood partly as a relationship between thyroid hormones and the overall level of physiological and neural activation.

With insufficient thyroid hormone, both bodily and neural processes can become less active. Possible consequences include:

Hypothyroidism → reduced metabolic and neural activity → fatigue, cognitive slowing, reduced motivation, and depressive symptoms.

With excessive thyroid hormone, physiological and neural activity can become heightened. Possible consequences include:

Hyperthyroidism → increased metabolic and neural activity → restlessness, anxiety, irritability, heightened emotional reactivity, and, in severe cases, manic-like symptoms.

The thyroid should therefore not be understood solely as a regulator of physical metabolism. Through its effects on cellular activity, cardiovascular function, neurotransmitter systems, and brain circuits involved in arousal, thyroid function can also influence cognition, mood, and behavior.

Reference:

WOW—a complicated subject explained clearly in just 14 minutes!
Thyroids by Prof. Robert Sapolsky 
https://www.youtube.com/watch?v=0o3-fEMrEuc

 

© 2000-2030 Sieglinde W. Alexander. All writings by Sieglinde W. Alexander have a fife year copy right.
Library of Congress Card Number: LCN 00-192742 ISBN: 0-9703195-0-9 

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