Clinical Depression Has Weak Association With Hypothyroidism

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Researchers conducted a systematic review and meta-analysis to assess the relationship between hypothyroidism and clinical depression.

The association between hypothyroidism and clinical depression was found to be weaker than prior research has suggested, according to the results of a systematic review and meta-analysis published in JAMA Psychiatry.

Hypothyroidism and depression share some symptoms, and prior meta-analyses have suggested the disorders may be linked.

In the current study (PROSPERO CRD42020164791), investigators searched MEDLINE, PubMed Central, PsycINFO, and Embase databases through May 4, 2020, for epidemiologic and population-based cohort and cross-sectional studies analyzing the incidence of hypothyroidism and depression. Case-control studies were excluded from the assessment.

Of the 25 studies (6 cohort and 19 cross-sectional; 348,014 participants; 53.6% women) the researchers included, 9 analyzed data of individuals with overt hypothyroidism, 17 analyzed data of individuals with subclinical hypothyroidism, and 9 analyzed data of individuals with thyroid autoimmunity.

Hypothyroidism and clinical depression were found to be linked (odds ratio [OR], 1.30). The association was higher (OR, 1.77) for overt hypothyroidism compared with subclinical hypothyroidism (OR, 1.13). Combined analysis found that the association was stronger in women (OR, 1.62) than in men (OR, 0.69). Post hoc analysis that solely included the 4 studies that compared men and women found that clinical depression and hypothyroidism were linked in women (OR, 1.48) but not in men (OR, 0.71).

Studies that were population-based, had cohort design, or included individuals taking thyroid medication or with a diagnosis of depression based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) or the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) had moderately stronger associations.

The cohort studies and 3 of the 19 cross-sectional studies had low risk of bias. When the researchers considered risk of bias, there was no longer a statistically significant association between hypothyroidism and clinical depression.

The researchers did not identify a link between autoimmunity and depression.

“It may be time to reconsider the paradigm of a strong connection between hypothyroidism and depression,” the investigators said. “The results of other groups and our own findings indicate the contribution of hypothyroidism to the pandemic of depression is probably small.”

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Bode H, Ivens B, Bschor T, Schwarzer G, Henssler J, Baethge C. Association of hypothyroidism and clinical depression: a systematic review and meta-analysis. JAMA Psychiatry. Published online September 15, 2021. doi:10.1001/jamapsychiatry.2021.2506