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Association of hypothyroidism with depression may depend on the severity of hypothyroidism and stronger in women

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There is a very complex association between hypothyroidism and depression. Patients with hypothyroidism and those with depression can present with similar general symptoms. A depressed mood is a common symptom of hypothyroidism. Autoimmune thyroid disease, the most common cause of hypothyroidism in the United States, may also affect the brain and induce depression. Also, hypothyroidism, being a chronic disease, could result in depression, like other chronic illnesses. Indeed, symptoms of depression are not always resolved when hypothyroidism is corrected. Also, hypothyroidism and depression can also occur at the same time in the same person. However, most hypothyroid patients do not develop depression and the majority of people with depression do not have hypothyroidism.

Both hypothyroidism and depression are more frequent in women than in men; however, it is still unknown if depression is more common in women with hypothyroidism. Previous studies performed using different methods have reported various results, from no association to a strong association between hypothyroidism and depression. This study aimed to investigate the existence and extent of an association between hypothyroidism, thyroid autoimmunity and clinical depression.

Bode H et al 2021 Association of hypothyroidism and clinical depression: A systematic review and meta-analysis. JAMA Psychiatry 78:1375–1383. PMID: 34524390.

The authors performed a search of large medical studies evaluating the association of hypothyroidism and depression from inception through May 2020. The study population for this study was representative of the general population. Of the 3372 articles identified in the initial search, 25 articles containing 348,014 participants were included in this study. Among these articles, 9 analyzed the association of depression with overt hypothyroidism, 17 with subclinical hypothyroidism, and 9 with positive TPO antibodies (TPOAb). A total of 15 studies assessed depressive symptoms using a standard depression score, and among these, 10 studies used the diagnostic coding of major depressive disorder by national criteria.

The average age of participants was 45 years, 56% of them being women. The study showed that there was a 1.3-fold increased risk to have depression with all degrees of hypothyroidism, ranging from a 1.13-fold risk in patients with subclinical hypothyroidism to 1.77-fold risk for patients with overt hypothyroidism. The risk was only seen in hypothyroid women (1.48-fold increase). TPOAb positivity was not associated with depression.

This study shows a moderate association of overt hypothyroidism, and less so of subclinical hypothyroidism, with clinical depression. The association was only seen in hypothyroid women. Thus, the contribution of hypothyroidism to the development of depression may be smaller than previously thought.

— Alina Gavrila, MD, MMSc


Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.

Subclinical Hypothyroidism: a mild form of hypothyroidism where the only abnormal hormone level is an increased TSH. There is controversy as to whether this should be treated or not.

Overt Hypothyroidism: clear hypothyroidism with an increased TSH and a decreased T4 level. All patients with overt hypothyroidism are usually treated with thyroid hormone pills.

Thyroid-stimulating hormone (TSH): a hormone produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.

Thyroxine (T4): the major hormone produced by the thyroid gland. T4 gets converted to the active hormone T3 in various tissues in the body.

Antithyroid peroxidase (TPO) antibodies: these are antibodies that attack the thyroid instead of bacteria and viruses, they are a marker for autoimmune thyroid disease, which is the main underlying cause for

Autoimmune thyroid disease: a group of disorders that are caused by antibodies that get confused and attack the thyroid. These antibodies can either turn on the thyroid (Graves’ disease, hyperthyroidism) or turn it off (Hashimoto’s thyroiditis, hypothyroidism).