Thyroid Hormone Mediates the Effect of Antidepressants on Cognitive Function in Patients with Depression: A Mediation Analysis in a Longitudinal Study

Abstract

Abstract Background: Patients with depression frequently experience cognitive impairment. Our purpose is to determine whether thyroid hormones mediate the effect of depression on cognitive impairment. Methods: A total of 119 depressed patients were enrolled (mean age 32 years, 56.30% female). The Montreal Cognitive Assessment Scale, the 17-item Hamilton Depression Scale, and thyroid hormone levels, including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), were evaluated at intervals of 8 weeks. In order to describe the temporal relationship between depression and cognitive impairment, we initially used cross-lagged panel analysis. After that, linear regression analysis was utilized to show how depression and thyroid hormones are related to one another. To further investigate the causal role of thyroid hormones in depression and cognitive impairment, a causal mediation model was created. Results: The cross-lagged panel analysis showed that there was a significant cross-lagged path coefficient from baseline depression to follow-up cognition(β=－0.284, P=0.002) . Baseline depression had an impact on FT3 (F = 1.880, P＜0.05) and FT4 (F = 2.466, P＜0.05), according to a linear regression analysis. Baseline depression were affected by baseline FT4 ( = 0.316, t = 2.687, P＜0.05). The link between baseline depression and follow-up cognitive performance was revealed to be partially mediated by serum FT4 levels, according to the causal mediation analysis (a=0.008, se=0.004, p=0.022, CI=0.001/0.016). Conclusion: Serum FT4 levels may be biological markers of cognitive impairment in patients with depression and may mediate the effect of depression on cognitive impairment.