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Thyroid Function & Depression: What is the Evidence?


Depression is a common but serious mood disorder. According to the World Health Organization, major depression is the mental health disorder with the largest burden of disability.[1] It can severely impair a person’s ability to function in everyday life, let alone achieve health and wellness.

The good news is that improving the function of one little organ could potentially help restore depressed patients to optimal health.

Thyroid Function in the Endocrine System

ThyroidThe thyroid gland is a critical part of the body’s endocrine system. It is a lobed, butterfly-shaped organ located in the front of the neck. It regulates a wide variety of functions in the body by releasing hormones into the bloodstream.

The two main hormones that the thyroid gland produces are T3 (Triiodothyronine) and T4 (Thyroxine).

The release of these hormones is regulated by thyrotropin (TSH) from the pituitary gland.[2] T3 and T4 increase metabolic rates; therefore, as the amounts of these hormones increase in the blood stream:

  • Body temperature rises
  • Heartbeat becomes stronger
  • Glucose stored in the liver and muscles breaks down to fuel energy
  • Growth is stimulated (in children/adolescents)[3]


When there are not enough thyroid hormones produced, metabolism slows. This is called hypothyroidism. If you have hypothyroidism your symptoms might include:

  • Fatigue
  • Weight gain
  • Constipation
  • Dry skin and hair
  • And sometimes depression

In fact, clinical depression occurs in over 40% of hypothyroid patients.[4]

Serotonin and Depression

It is well known that the monoamine neurotransmitters, particularly serotonin, are vitally important in the modulation of mood and the symptomology of depression.[5]

Nearly all clinical treatments for depression including SSRIs, tricyclic antidepressants, and MAO inhibitors manipulate serotonin activity in the brain.[6]

More serotonin leads to better moods, but patients with depression are often deficient in this key neurotransmitter.

Serotonergic Transmission and Thyroid Function

But what does that organ in our necks have to do with depression? Researchers have found that thyroid hormones affect serotonergic transmission in the brain.

Studies have shown that induced hypothyroid states in animals led to decreased levels of serotonin in the cortex of the brain.[7]

These induced hypothyroid states also reduced 5-HT2A receptor density.[8] This is an excitatory serotonin receptor subtype, so the fewer receptors there are, the less serotonergic transmission occurs.

This suggests that hypothyroidism may cause lowered serotonin levels in the brain which can lead to symptoms of depression.

Furthermore, treatment with thyroid hormones could help to alleviate depression.

Treating Thyroid Function and Depression

Patients with depression and no other illnesses often have low T3 hormone levels.[9] One study has shown that lower T3 and T4 concentrations in patients with major depression were significant predictors of worse clinical improvement in their symptoms.[10]

Thyroid hormone treatment in rats produced an increase in both serotonin and its precursor, 5-HTP, in the cortex of the brain in 10 different studies.[11] Higher serotonin is often indicative of better mood and decreased symptoms of depression.

Thyroid hormones most likely increase serotonergic transmission by reducing the sensitivity of inhibitory 5-HT1A autoreceptors[12] and increasing the sensitivity of excitatory 5-HT2A receptors.[13]

T3 Supplementation and Atypical Depression

This is exciting news for patients with depression! Thyroid hormone treatment could actually help alleviate their symptoms.

Several double-blind placebo controlled studies showed that T3 supplementation was effective in speeding up the rate of patient response to tricyclic antidepressants.[14] It has been hypothesized to be helpful for patients with atypical depression (depression with excessive appetite, sleeping, and fatigue).[15]

According to the American Association of Clinical Endocrinologists, “The diagnosis of subclinical or clinical hypothyroidism must be considered in every patient with depression”.[16]

This recommendation serves as a reminder that our bodies affect our brains and vice versa. In the future more research on the relationship between hypothyroidism and depression will surely improve clinical outcomes for depressed patients and further our knowledge of the HPA-T Axis.



[1] National Institute of Mental Health (2014). Major Depression Among Adults. Retrieved from

[2] National Center for Biotechnology Information. (2015). How does the thyroid work? Retrieved from

[3] Ibid.

[4] Hage MP & Azar ST. (2012). The Link between Thyroid Function and Depression. Journal of Thyroid Research, 2012, 590648. Retrieved from

[5] Bauer M, Heinz A, & Whybrow PC. (2002). Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain. Molecular Psychiatry, 7, 140–156.

[6] Ibid.

[7] Ibid.

[8] Ibid.; Kulikov A, Moreau X, & Jeanningros R. (1999). Effects of experimental hypothyroidism on 5-HT 1A,5-HT 2A receptors, 5-HT uptake sites and tryptophan hydroxylase activity in mature rat brain. Neuroendocrinology. Neuroendocrinology, 69, 453-459; Berent D, Zboralski K, Orzechowska A, et. al. (2014). Thyroid hormones association with depression severity and clinical outcome in patients with major depressive disorder. Molecular Biology reports, 41:2419–2425.

[9] Hage op. cit.

[10] Berent op. cit.

[11] Bauer op. cit.

[12] Ibid.

[13] Ibid., Kulikov op. cit., Berent op. cit.

[14] Hage op. cit.

[15] Ibid.

[16] Ibid.


Clinical Contributor

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Ramona Richard, MS, NC

Ramona Richard, MS, NC

Ramona Richard graduated with honors from the University of California with a Bachelor’s Degree in psychology and graduated summa cum laude with a Master’s Degree in Health and Nutrition Education. She also holds a Standard Designated Teaching Credential from the State of California, is a California state-certified Nutrition Consultant and a member of the National Association of Nutrition Professionals.

Ramona has participated in nutrition education in both public and private venues, including high school and college presentations, radio and public speaking for the past 20 years. She is the owner of Radiance, a nutrition consulting company, the Director of Education for Sanesco International, and a medical technical writer.

Disclaimer: The information provided is only intended to be general educational information to the public. It does not constitute medical advice. If you have specific questions about any medical matter or if you are suffering from any medical condition, you should consult your doctor or other professional healthcare provider.

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