Thyroid hormone levels in patients with bipolar disorder: a systematic review and meta-analysis

To investigate the difference in blood (serum/plasma) thyroid hormone (TH) levels, including thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3), in bipolar disorder (BD) during different mood episodes (depression and mania) compared with healthy control (HC) and between manic episodes (BD-M) and depressive episodes (BD-D).

As of September 1, 2024, the electronic databases PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, China Science and Technology Journal Database, Wanfang Database, and Clinical Trials. Gov were systematically searched with no language limitations. Standardized mean differences (SMD) with 95% confidence interval (CI) were summarized using a random effects model. The chi-squared-based Q test and the I² test assessed the size of heterogeneity.

The 21 studies included a total of 3696 participants, Of the 2942 BD patients, 1583 were in depressive episodes 1359 were in manic episodes. The status of measuring blood TH levels included 2 studies in plasma and 19 in serum. Combined with the results of the sensitivity analyses, we obtained the following relatively reliable results: serum T3 (SMD: -0.63, 95%CI: -1.09 to -0.17) and FT3 (SMD: -0.42, 95%CI: -0.83 to -0.00) levels decreased significantly in BD-D compared to HC; serum T3 (SMD: -0.91, 95%CI: -1.49 to -0.32) levels decreased significantly and serum FT4 (SMD: 0.37, 95%CI: 0.14 to 0.60) levels increased significantly in BD-M than in HC; serum T3 (SMD: 0.87, 95%CI: 0.24 to 1.49) and FT3 (SMD: 0.27, 95%CI: 0.13 to 0.42) levels demonstrated a significant elevation in BD-M compared to BD-D. In the group of euthyroidism, apart from serum FT4 (SMD: 0.21, 95%CI: -0.15 to 0.58) levels showed no significant difference between BD-M and HC, other results above remained consistent.

Serum T3 and FT3 levels decreased significantly in BD-D compared to HC. Serum T3 levels decreased significantly and serum FT4 levels increased significantly in BD-M compared to HC. Serum T3 and FT3 levels increased significantly in BD-M than in BD-D. The temporality of changes in TH levels and BD progression demands further longitudinal studies to illustrate.

Number and date of registration for prospectively registered trials No. CRD42022378530.