Does the Thyroid Gland Play a Role in Depression, Anxiety and Psychosis? – Is the TSH enough to diagnose thyroid dysfunction?

Ever wondered if your thyroid gland is playing a role in your depression, anxiety or psychosis? A month ago, I saw a 24 year old male who was admitted for increasing feelings of low mood and thoughts of suicide. On assessment, he showed symptoms of severe depression with no psychosis. Further investigations revealed a TSH of 5.5 and a normal T4 and T3. An endocrine referral was made and the endocrinologist told me this is “mild subclinical hypothyroidism”. Whilst this is true from the endocrinologist’s perspective, does it hold true from the psychiatrist’s perspective? And….what about the patient?

One would agree that from a patient’s perspective the depression is distressing . This is not an uncommon story, in fact it happens time and time again in clinical settings where  depressed patients who have had repeated ECTs with no improvement when evaluated for thyroid,  have thyroid abnormalities.

In another example, a post menopausal woman with a diagnosis of treatment resistant paranoid schizophrenia was on high dose typical antipsychotics. Her symptoms included depressive symptoms, delusions of nihilism and persecution. On clinical assessment, she showed signs and symptoms of hypothyroidism with her TSH level at 4.5 (normal lab range in the hospital was 0.5-5) with normal T4 and T3.

In a third case, a 22 year old female who was being treated for depression with citalopram continued to complain of poor energy levels and ongoing low mood. On history taking she had a number of symptoms of hypothyroidism, most notably thinning of hair with hair loss, fatigue and menstrual abnormalities; all of which have been exacerbated after her first pregnancy. Her TSH levels were 2.3 with normal T3 and T4 (but at the lower end of normal).

So how were these patients treated? The young male showed rapid improvement with thyroid replacement (Thyroxine) in a matter of a few days. He did not require any antidepressants. For the second patient, I initiated Thyroxine based on her clinical presentation and she responded to thyroid replacement of 50mcg in a matter of a week with her delusions remitting completely in two weeks. Furthermore, we were able to reduce the typical antipsychotic dose which led to further improvements in mood. In the third case, I considered the hypothesis of possible hypothyroidism based on the clinical picture and prescribed a two week trial of 50 mcg of Thyroxine as an augmentation agent with the Citalopram. She showed a dramatic improvement in a week and particularly reported a decrease in her fatigue and improved motivation.

The response in all three cases is noticeably striking due to the rapidity of response. Note that in the latter two cases, the TSH levels were within the normal lab range, yet they responded. These are infact just three of several cases that respond brilliantly to Thyroid Replacement Therapy (TRT) when a careful clinical assessment reveals signs and symptoms of hypothyroidism. Monitoring of the TSH to avoid hyperthyroidism and a close collaboration with the GP and if possible an endocrinologist is important.

So why is there such a divide in what the endocrinologists regard as thyroid dysfunction and what the psychiatrists should use as a guide to treatment? The answer lies in three main points;

a. The misunderstanding of the working of the thyroid and its effect on the brain.(see below)

b. The misapplication of screening and diagnostic tests: A TSH is a screening test and was validated in an endocrine population and not a psychiatric population. Critical Appraisal 101 tells us that a screening test should always be validated in the population in which we intend to use the test.

c. The lack of understanding of the concepts of Positive Predictive Value (PPV) and Negative Predictive Value (NPV): Positive Predictive value helps us answer the question “If I tested positive on the test, what is the probability I have the disease” whilst negative predictive value helps us exclude the disease. Both NPV and PPV change with prevalence. Thus a test that can predict and exclude disease well in a highly prevalent population( e.g endocrine medical wards for hypothyroidism) may perform poorly in a low prevalence population (e.g. psychiatric population for hypothyroidism). 

 We will touch on the understanding of the thyroid gland and its effect on the brain in a bit more detail.

Understanding of the Working of the Thyroid Gland and Its Effect on Tissues :

Firstly let’s see how the thyroid hormone acts in each organ. Dr David Derry (Specialist Endocrinologist) sums it up brilliantly in the following interview (edited). “To start with, the thyroid metabolism is controlled locally in the tissue by each organ (By Deiodinases). The brain has one mechanism for controlling the amount of thyroid available to the brain but it is different from other tissues such as the liver.  The problem with this is– if a tissue needs more (such as the brain with depression) there is no way for the brain to signal the thyroid that it needs more sent up to it. The thyroid merrily goes on putting out the same amount of thyroid hormone. So the patient can have symptoms related to low thyroid in the brain (for example) but the thyroid doesn’t do anything about it. But if you give thyroid hormones in an adequate dose the brain symptoms will disappear. Meanwhile the other tissues and organs adapt to the increased circulating hormones that you have used to fix the brain with.  But because of the all inclusiveness of the TSH, medical students are not taught or only superficially taught the symptoms of low thyroid. The TSH was “scientific” and held all the answers to thyroid disease. If you have not lived through several versions of the ultimate test for thyroid then it is harder to grasp this phenomenon.”  The full interview can be read here.

Secondly, in order to treat depression through the serotonin pathway, the thyroid is an important part of the equation via an increase in serotonergic neurotransmission, specifically by reducing the sensitivity of 5-HT1A autoreceptors in the raphe area, and by increasing 5-HT2 receptor sensitivity. (Bauer M, 2002, Mol Psychiatry).

Thirdly, thyroid hormones are present in different concentrations in brain tissue and peripheral tissues. In contrast to peripheral tissue where T4 concentrations usually far exceed those of T3, in the brain T4 and T3 concentrations are in an equimolar range. (Bauer M, 2002, Mol Psychiatry) The entire article by Bauer et al. published in Molecular Psychiatry can be read here.

You will appreciate that a single TSH range does not encompass the abnormalities of thyroid in the different tissues in the body. Simply put, a TSH can be normal, despite the individual having a number of symptoms. The brain has a very high density of thyroid receptors (amongst the highest of any organ) and is extremely susceptible to mild changes in the thyroid hormone.

Take home message: treat the person, not the blood test. Focus on taking a good clinical history of the thyroid system and perform an examination. Metabolic abnormalities such as dyslipidemia are also a part of hypothyroidism and can add weight to your hypothesis. Treating hypothyroidism proactively is important to avoid labelling the individual as treatment resistant and exposing them to polypharmacy. The conundrum can often be solved by a diagnostic and therapeutic trial of thyroid replacement therapy (TRT). In an ideal world, it would be great to involve an endocrinologist or a GP in the management of thyroid dysfunction, but as we know, this is not always possible. Hence there a need for psychiatrists to be accountable for treating basic medical conditions.

Read the next part of the thyroid and psychiatry conundrum with these interesting facts about the thyroid gland and psychiatry.

This article is written by Dr Sanil Rege. Sanil is a Consultant Psychiatrist in Mornington, Victoria and co-founder of He is pursuing an MBA at the Melbourne Business School.  You can follow him on Google+

2 Responses to "Does the Thyroid Gland Play a Role in Depression, Anxiety and Psychosis? – Is the TSH enough to diagnose thyroid dysfunction?"

  1. Lynn says:

    As someone who has suffered from depression and Hashimoto’s hypothyroid without proper treatment for many years, I appreciate your article and am happy to see that some doctors out there are finally acknowledging a connection. I am a moderator in an autoimmune thyroid group and many are familiar with the benefits of the right amount of meds on improving psychological states. I never thought I’d get past the depression, but I consider myself free from it now and it was due to learning how to address my thyroid issue along with some autoimmune triggers. Thank you for posting this article.

  2. Hi Lynn,
    Thank you for your comment. Autoimmune thyroid and Autoimmune conditions in general are becoming increasingly important in psychiatry. Links between Vit D, Autoimmunity , Thyroid etc are all links that are slowly coming to light, putting greater onus on the doctor to take a holistic view of the patient and looking at all aspects of “disease”genesis. Simply putting a name to the condition, may not be enough; getting to the core issue is crucial to achieve remission. I will be posting more about these issues in due time.

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