How does your thyroid affect your mood?
Not feeling like yourself? Struggling with fatigue, trouble concentrating, and depression? It could be your thyroid. The symptoms of depression and hypothyroidism overlap by quite a bit and thyroid medication has long been known for helping with depressive symptoms.
How likely is it that you have a thyroid condition if you experience depressive symptoms? This is difficult to put a number on for several reasons. First, depression is not caused by just one thing, but can result from many different processes in the body. The symptom of depression is one way your body can tell you that something within you is needing attention. This article will focus on your thyroid specifically, and will explain how an unhappy thyroid can vie for your attention by contributing to symptoms of depression.
You’ve asked some great questions on this topic, and the following will be answered in this article:
Where is your thyroid, and what does it do?
How do thyroid hormones work in the brain?
How do thyroid hormones affect your mood?
Can hyperthyroidism contribute to depression too?
Do thyroid hormones play a role in postpartum depression?
Can thyroid hormone medications help depression?
Is it the thyroid hormones or the autoimmune process itself?
Do antidepressants affect thyroid hormones?
Let’s start with a quick intro on where your thyroid is, and what it does for you.
Where is your thyroid, and what does it do?
Your thyroid gland sits on your neck. People like to describe it as a butterfly shape, but if your thyroid is misbehaving, it may be larger (or more nodular) than any butterfly you’ve ever seen! When it is behaving, it’s business as usual and your cells are able to do their jobs.
It’s hard to even know where to start when describing exactly what your thyroid does, because it is so vital to so many functions within your body. Thyroid hormones affect gene expression which in turn affects, well, everything. They affect how your body uses energy. They play a role in metabolism, weight maintenance, lipid balance, mood, concentration and cognition, digestion and how your heart beats. They also socialize with your other hormones and your circadian rhythm.
When you have less thyroid hormone than optimal, this is called hypothyroidism and you will have an increased TSH. The TSH will be increased because this is your body’s way of asking your thyroid for more hormone.
When you have more thyroid hormones than optimal, this is called hyperthyroidism and you will have a decreased TSH. The TSH will be decreased because this is your body’s way of saying it doesn’t need any more thyroid hormones.
How do thyroid hormones work in the brain?
The relationship between thyroid hormones and your susceptibility to depressive symptoms begins before you are even born! Your mother’s thyroid functioning during pregnancy has an impact on both depression and other mental health related symptoms. [1] Obviously you can’t go back in time and change this, so let’s focus on what you can work on, which is keeping your thyroid healthy now.
Thyroid hormones have many functions within the brain. These include, but are not limited to, neuronal processing, glial cell proliferation, myelination, and neurotransmitter synthesis. [2]
There are several deiodinase enzymes that affect your levels of thyroid hormones.
Type 1 iodothyronine deiodinase helps produce T3 hormone. This is found in multiple places, including your liver and kidneys.
Type 2 iodothyronine deiodinase works to convert your T4 hormone to T3 hormone. It can be found in several places, including the astrocytes in your brain.
Type 3 iodothyronine deiodinase helps get rid of T4 by converting it to reverse T3 or T2 hormone. Type three is expressed in many areas of the body, including neurons in the brain, and it may be protective against inflammation.
T3 hormone is your most highly “active” thyroid hormone. It can arrive in your brain through the circulation, or it can be produced by the type 2 enzyme in your astrocytes. When mice in the lab have that type 2 enzyme inactivated in their astrocytes, they have normal T3 levels in their blood but demonstrate the lab mice equivalent of “anxiety” and “depression”-like behaviour. [3] These effects occurred along with changes in gene expression. One of the genes affected is that of BDNF (brain derived neurotrophic factor), which is involved in cognitive function and related to depressive symptoms.
The most interesting thing this study showed was that exercise was able to rescue the changes in gene expression, despite the majority of the type 2 enzyme being inactivated! [3] You’ve probably heard the benefits of exercise for mental health many times by now, but now you know one more reason for why it can be effective! It was also cool to note that in the mice who still had type 2 enzyme activity, exercise increased its activation.
The expression of the type 1 and 3 enzymes has been studied in patients with recurrent depression. In these people, type one enzyme levels were significantly lower, whereas type three enzyme levels were significantly higher compared to healthy controls. These lower type 1 enzyme levels may help explain the association of depression and hypothyroidism. [4]
Why might these enzymes levels be different in people with depressive symptoms? Type one enzymes might be low as a result of glucocorticoid levels or certain cytokines (immune system messengers). In these cases, it is helpful to take a look at cortisol levels, inflammation, and hidden infections. Elevations of type 3 enzyme levels may be a result of inflammation or infection as well, and can be expressed in immune cells. [4]
As you can see, the thyroid hormone levels in your brain partly depend on the levels in circulation in your body, and partly depend on the expression of local iodothyronine deiodinase enzymes, which help to maintain appropriate levels of hormone in the area. For example, in a hypothyroid state, your body can increase activity of the type 2 enzyme and decrease the activity of the type three enzyme, effectively increasing T3 levels.
A third factor is the membrane transporters that act to bring thyroid hormones into the brain from circulation.
There’s also another side to this story: your circadian rhythm. Normally, you have more TSH secretion at night than in the morning. In people with clinical depression, the difference between TSH in the morning and in the evening is blunted compared to those without symptoms of clinical depression. When given treatment, those whose circadian TSH secretion normalizes again within two weeks are more likely to show clinical improvements in mood later on. This means that re-establishing normal circadian activity of thyroid hormones is an important indicator of treatment response. [5]
How do thyroid hormones affect your mood?
Some studies conclude that there is no increased risk of depression amongst those with hypothyroidism. [For example, 6] However, when reading up on the research regarding thyroid conditions, it is important to check the “normal” range they are using for these hormones. If they are counting any TSH up to 5 as “normal”, they aren’t really separating the “healthy” from the “hypothyroid” groups, as this number is much higher than optimal.
When studies instead look at TSH groupings from lowest to highest, they find that, in women, both the lowest TSH levels and the highest TSH levels (even within “normal” lab reference ranges) are associated with depression. [7] I note this occurred in women, because the link between thyroid function and depression in this particular study was not found in men. [7] Hypothyroidism also significantly increases the risk for depression in older people [8].
In addition to this, it has long been known that thyroid medications can help with depressive symptoms. What is not as well-known is exactly how they exert their therapeutic effects in this context. One possible reason for this is the interaction of thyroid hormone with your neurotransmitters.
Let’s consider serotonin as an example.
Most of the research in this area comes from animal studies, so take it with a grain of (low iodine) salt because while helpful, animal studies don’t always directly translate to how things work in humans!
In animals, thyroid hormone affects the levels of serotonin and its metabolites in the brain. Removing the thyroid dropped the level of serotonin and increased the level of its metabolite 5-HIAA. Giving thyroid hormone replacement to these animals helped restore the balance of serotonin turnover. [2]
In line with this, patients who are in a hyperthyroid state and thus have too much thyroid hormone, have elevated serotonin levels with decreased activity of monoamine oxidase enzyme (likely a protective response to the elevated serotonin). [2]
There are also ties between thyroid hormones and catecholamines (dopamine, norepinephrine and epinephrine), all of which are made from the same amino acid, tyrosine. [9,10] In fact, a study published within the last few months found that thyroid hormone derivatives may be useful for dopamine neuron differentiation and as a result, could be considered in the treatment of Parkinson’s disease, a condition known to be related to a loss of dopamine neurons. [11]
Alterations in GABA levels (typically known as your calming neurotransmitter) have also been noted in people with hypothyroidism. [12]
Aside from neurotransmitters, thyroid hormones are also incredibly important for the development of the brain. In adults, disturbances of thyroid hormones are associated with a wide variety of mental health conditions – not just depression!
Why is this?
Thyroid hormones in the brain have effects on several different types of brain cells. They can affect the stimulation or degeneration of microglial cells, an important part of your brain’s immune system, and microglial dysfunction has been linked to mental health conditions. They can also affect myelination (oligodendrocytes and astrocytes), which is important for making sure there is good communication within your brain. [13]
Can hyperthyroidism affect depression too?
Yes! Untreated hypothyroidism is associated with depression, and so is untreated hyperthyroidism. [14,15] This is interesting because usually you will hear about hypothyroidism (low thyroid function) and depression.
A Danish study from a few years ago found that people with a suppressed TSH (in this case meaning a hyperthyroid state) did have a slightly increased prevalence of subclinical depression. [16] Some studies actually find a more significant relationship between hyperthyroidism and depression than they do for hypothyroidism and depression. I doubt this is an accurate finding, as the TSH reference ranges used in these studies were far from optimal. [For example, 15]
Lithium is a therapy sometimes used in the treatment of a hyperthyroid state, and is also used (although in much higher doses) as a mood stabilizer in the treatment of affective disorders. These effects on the thyroid may be helpful if you are in a hyperthyroid state, but could exacerbate things if you are in a hypothyroid state.
Do thyroid hormones play a role in postpartum depression?
During pregnancy, your immune system has to relax its vigilance for invaders to allow for the presence of a new (and foreign to you!) human. As a result, there are shifts in your immune system throughout a pregnancy, and once the baby is born, your body is expected to return to its “normal” state of immune activity. Sometimes, your immune system swings back a little too far to the vigilant side, increasing the risk for autoimmune conditions like Hashimoto’s thyroiditis. What else is there an increased risk for postpartum? Depression. And there are a large number of reasons for this, but let’s stay focused on the thyroid for now.
Multiple studies have noted a link between thyroid antibodies and depression at various timepoints throughout and after a pregnancy. [17] In particular, the presence of anti-thyroid peroxidase antibodies early in a pregnancy increases the risk for first time depression in the first four months after the baby is born. [18] Why this timing? The antibodies decline throughout pregnancy as the immune system becomes more tolerant, but once the baby is born there is a rebound in immune activity and antibody levels rise again. Postpartum depression in women with positive TPO antibodies reflects the timing of this rise. [18]
Aside from the immune system, there are also significant hormone fluctuations throughout a pregnancy. This includes changes in thyroid hormones. An elevated TSH level prior to pregnancy is predictive for postpartum depression. [19] Changes in thyroid hormones can affect serotonin levels, but they also have bidirectional effects on estrogen, which is of note since female hormones are also undergoing significant changes postpartum. In addition, lower levels of thyroid binding globulin in the third trimester of pregnancy were found to be a predictor of postpartum depression.
The thyroid binding globulin concentration is thought to be a marker of estrogen sensitivity, as estrogen affects the degradation of thyroid binding globulin. [20] In these mothers, it is hypothesized that lower sensitivity to elevated estrogen may give an increased vulnerability to elevated progesterone levels during this timeframe, leading to depressive symptoms. [20]
Not all studies agree on a link between thyroid health and postpartum depression, but a wide variety of methods have been used to study this, and they are not all comparable. In a longer-term study looking at these two conditions in the two years postpartum, autoimmune thyroid disease and postpartum depression were over two times more likely to occur together than separately. [21] At the end of the day, it is important to take a look at your unique situation and evaluate the best options for you based on your own labs and symptoms.
Can thyroid hormone medications help depression?
Recall from above that it was untreated hypothyroidism that was associated with depression. In this study, the link between diagnosed hypothyroidism and depression lost strength when they included those taking medications in the statistical analysis. [14] If you have hypothyroidism, medication may help with symptoms of depression. For example, another study showed thyroid medication to be effective in relieving the somatic symptoms (somatic meaning bodily) of depression, and improving scores on the Beck Depression Inventory. [22]
Treating hypothyroidism is also important for preventing depression, as hypothyroidism can result in lipid disturbances and increase risk for cardiovascular disorders, which are in turn associated with depression. [23]
If your thyroid medication has not resulted in improvements in your mood there could be several reasons for this. First, you may need a different type of medication. Not all thyroid medications are created equal, some are allowed more variance in the manufacturing than others, and some contain T3 while others are solely T4. Working with a practitioner that understands these subtleties is important. It could also be that your TSH is not yet at an optimal point. There is a Goldilocks range here, you want just enough, not too much and not too little.
Another possibility is that there is something other than your thyroid contributing to your symptoms. This could be another process within the body, such as an infection or low iron stores (which can also affect your thyroid!) but it could also be something in your life, like a major stressor (whether good or bad!) or a lack of sleep.
In addition, some thyroid conditions, like Hashimoto’s thyroiditis, are autoimmune conditions. This means that your body has accidentally mounted an attack against itself. While thyroid antibodies fluctuate widely over time and are not always helpful beyond diagnosis, in some cases the autoimmune process could contribute to your symptoms. Let’s unpack this idea next.
Is it the thyroid hormones or the autoimmune process itself?
There are three important components to an autoimmune thyroid disease: how it affects your thyroid hormones, how it affects your TSH, and the autoimmune process itself. Each of these can contribute to the symptoms you experience.
You just learned how thyroid hormones affect the brain, but how does the actual autoimmune process affect the brain? Well in a more extreme example, some people with Hashimoto’s thyroiditis can experience something called Hashimoto’s encephalopathy. This condition is associated with neurological symptoms like tremors or walking differently or seizures. However, it has also been shown that it can present with depression as its main symptom. [24] When this occurs it is treated with steroids, and improvement on this therapy helps confirm the diagnosis.
Autoimmune processes across a wide variety of autoimmune conditions have been proposed to contribute to depressive symptoms. There may be an increased risk for depression in some of these conditions, however, one study that looked at antibody levels over time found that antibody levels were not associated with increased risk of developing depression over the five year timeline of the study. [25] This study was performed in a general population of healthy adults. It may be that studies looking at people with severe autoimmune disease or severe clinical depression would have different conclusions.
There may be a relationship between increased TPO antibodies and recent depression in those with hypothyroidism (regardless of whether they are on a thyroid medication), but not all studies are in agreement with this. [14,26,27] An association has also been found between the thyroid receptor autoantibodies that you get in Graves’ disease and depression severity. [28] In patients with Graves’ disease who undergo treatment for Graves’ and later experience hypothyroidism, thyroid peroxidase antibodies have also been shown to be a risk factor for depression. [29]
How could antibodies against your thyroid also affect your brain? In Hashimoto’s encephalopathy, high levels of anti-thyroperoxidase antibodies are found in the cerebrospinal fluid (the fluid that helps cushion your brain), and these antibodies have also been shown to bind to astrocytes (a type of brain cell). High levels of these antibodies have not been shown to occur in the cerebrospinal fluid of people with Hashimoto’s thyroiditis only. [30]
Further research will help to clarify this association. Perhaps the antibodies really are associated with depression, but only in certain patients, such as those with postpartum depression, Hashimoto’s encephalopathy or conditions that could facilitate access of these antibodies to the brain.
Do antidepressants affect thyroid hormones?
In the section on hyperthyroidism, you learned how the commonly used mood stabilizer can affect thyroid hormones. Curiously, selective serotonin reuptake inhibitors (SSRIs) can also have effects on thyroid hormones. For example, in one published case report, the SSRI fluoxetine was given for depression, and the patient’s lab work suddenly showed hyperthyroidism. This resolved when the fluoxetine was discontinued, and the patient started a different antidepressant medication. [31]
Another study compared the effects of reboxetine, venlafaxine and sertraline on thyroid hormones. In this study, venlafaxine did not have any significant effects on TSH. However, reboxetine decreased TSH and sertraline increased TSH. The reboxetine-associated change in TSH was related to decreases in depressive symptoms scores. [32]
This is an interesting study because each of these antidepressants has a different mechanism of action, and it appears that they each affect thyroid hormones differently too. Whether or not this is helpful may depend on where your thyroid health was at before you began antidepressant medication. The average TSH in this study was a little higher than optimal before the patients started their medications. However, in the previous case study example, where fluoxetine triggered hyperthyroidism, the initial TSH was already closer to optimal which gave less room for it to decrease before hitting a hyperthyroid range.
If you are on antidepressant medication it could be helpful to regularly check in on your thyroid hormones.
Final Thoughts
Your thyroid hormones are important to a wide variety of processes in your body. As such, it should be no surprise that they can also play a role in your mood. Getting your hormones back on track could be a good first step toward your health goals!
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References
1. Endendijk, J. J., Wijnen, H. A. A., Pop, V. J. M. & van Baar, A. L. Maternal thyroid hormone trajectories during pregnancy and child behavioral problems. Horm. Behav. 94, 84–92 (2017).
2. Bauer, M., Heinz, A. & Whybrow, P. C. Thyroid hormones, serotonin and mood: Of synergy and significance in the adult brain. Molecular Psychiatry vol. 7 140–156 (2002).
3. Bocco, B. M. L. C. et al. Type 2 deiodinase disruption in astrocytes results in anxiety-depressive-like behavior in male mice. Endocrinology 157, 3682–3695 (2016).
4. Gałecka, E. et al. Assessment of type 1 and type 3 deiodinase expression levels in depressive disorders. Acta Neurobiol. Exp. (Wars). 77, 225–235 (2017).
5. Duval, F. et al. Chronobiological hypothalamic–pituitary–thyroid axis status and antidepressant outcome in major depression. Psychoneuroendocrinology 59, 71–80 (2015).
6. Kim, J. S. et al. Subclinical Hypothyroidism and Incident Depression in Young and Middle-Age Adults. J. Clin. Endocrinol. Metab. 103, 1827–1833 (2018).
7. Kim, E. Y. et al. Relationship between thyroid-stimulating hormone levels and risk of depression among the general population with normal free T4 levels. Psychoneuroendocrinology 58, 114–119 (2015).
8. Chueire, V. B., Romaldini, J. H. & Ward, L. S. Subclinical hypothyroidism increases the risk for depression in the elderly. Arch. Gerontol. Geriatr. (2007) doi:10.1016/j.archger.2006.02.001.
9. HARRISON, T. S. ADRENAL MEDULLARY AND THYROID RELATIONSHIPS. Physiological reviews (1964) doi:10.1152/physrev.1964.44.2.161.
10. Whybrow, P. C. & Prange, A. J. A Hypothesis of Thyroid-Catecholamine-Receptor Interaction: Its Relevance to Affective Illness. Arch. Gen. Psychiatry (1981) doi:10.1001/archpsyc.1981.01780260108012.
11. Lee, E. H. et al. Dopamine neuron induction and the neuroprotective effects of thyroid hormone derivatives. Sci. Rep. (2019) doi:10.1038/s41598-019-49876-6.
12. Liu, B. et al. Investigation of brain GABA+ in primary hypothyroidism using edited proton MR spectroscopy. Clin. Endocrinol. (Oxf). 86, 256–262 (2017).
13. Noda, M. Possible role of glial cells in the relationship between thyroid dysfunction and mental disorders. Frontiers in Cellular Neuroscience (2015) doi:10.3389/fncel.2015.00194.
14. Ittermann, T., Völzke, H., Baumeister, S. E., Appel, K. & Grabe, H. J. Diagnosed thyroid disorders are associated with depression and anxiety. Soc. Psychiatry Psychiatr. Epidemiol. 50, 1417–1425 (2015).
15. Hong, J. W., Noh, J. H. & Kim, D.-J. Association between subclinical thyroid dysfunction and depressive symptoms in the Korean adult population: The 2014 Korea National Health and Nutrition Examination Survey. PLoS One 13, e0202258 (2018).
16. Kvetny, J., Ellervik, C. & Bech, P. Is suppressed thyroid-stimulating hormone (TSH) associated with subclinical depression in the Danish General Suburban Population Study? Nord. J. Psychiatry 69, 282–286 (2015).
17. Dama, M., Steiner, M. & Lieshout, R. Van. Thyroid peroxidase autoantibodies and perinatal depression risk: A systematic review. J. Affect. Disord. 198, 108–121 (2016).
18. Wesseloo, R., Kamperman, A. M., Bergink, V. & Pop, V. J. M. Thyroid peroxidase antibodies during early gestation and the subsequent risk of first-onset postpartum depression: A prospective cohort study. J. Affect. Disord. 225, 399–403 (2018).
19. Sylvén, S. M. et al. Thyroid function tests at delivery and risk for postpartum depressive symptoms. Psychoneuroendocrinology 38, 1007–1013 (2013).
20. Pedersen, C. et al. Late pregnancy thyroid-binding globulin predicts perinatal depression. Psychoneuroendocrinology 65, 84–93 (2016).
21. Bergink, V. et al. Comorbidity of autoimmune thyroid disorders and psychiatric disorders during the postpartum period: a Danish nationwide register-based cohort study. Psychol. Med. 48, 1291–1298 (2018).
22. Najafi, L. et al. Depressive symptoms in patients with subclinical hypothyroidism – the effect of treatment with levothyroxine: a double-blind randomized clinical trial. Endocr. Res. 40, 121–126 (2015).
23. Sher, Y., Lolak, S. & Maldonado, J. R. The impact of depression in heart disease. Current Psychiatry Reports vol. 12 255–264 (2010).
24. Endres, D., Perlov, E., Stich, O. & Tebartz van Elst, L. Steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) presenting as major depression. BMC Psychiatry 16, 184 (2016).
25. Iseme, R. A. et al. Autoantibodies are not predictive markers for the development of depressive symptoms in a population-based cohort of older adults. Eur. Psychiatry 30, 694–700 (2015).
26. Delitala, A. P. et al. Depressive symptoms, thyroid hormone and autoimmunity in a population-based cohort from Sardinia. J. Affect. Disord. 191, 82–87 (2016).
27. Yalcin, M. M. et al. Is thyroid autoimmunity itself associated with psychological well-being in euthyroid Hashimoto’s thyroiditis? Endocr. J. 64, 425–429 (2017).
28. Fam, J. et al. Thyroid autoimmune antibodies and major depressive disorder in women. Ann. Acad. Med. Singapore (2015).
29. Yu, J., Tian, A.-J., Yuan, X. & Cheng, X.-X. Subclinical Hypothyroidism after 131I-Treatment of Graves’ Disease: A Risk Factor for Depression? PLoS One 11, e0154846 (2016).
30. Blanchin, S. et al. Anti-thyroperoxidase antibodies from patients with Hashimoto’s encephalopathy bind to cerebellar astrocytes. J. Neuroimmunol. (2007) doi:10.1016/j.jneuroim.2007.08.012.
31. Lai, J. et al. Reversible Fluoxetine-Induced Hyperthyroidism. Clin. Neuropharmacol. 39, 60–61 (2016).
32. Eker, S. S. et al. Effects of various antidepressants on serum thyroid hormone levels in patients with major depressive disorder. Prog. Neuro-Psychopharmacology Biol. Psychiatry 32, 955–961 (2008).