Background Hypothyroidism is linked to depression and several metabolic alterations, including insulin resistance, dyslipidemia, and oxidative stress. This study investigates the impact of hormones, autoimmunity, metabolic, and antioxidant indicators on the severity of depression in patients with hypothyroidism.

Methods Forty-six patients with hypothyroidism and seventy-four with Hashimoto’s thyroiditis participated in this study, along with sixty healthy controls. Patients were categorized based on the Hamilton Depression Rating Scale (≥ 17) into those with depression and those without. The enzyme- linked immunosorbent assay method was employed to evaluate blood insulin and selenoprotein P (SePP). Graphite furnace atomic absorption spectrophotometry was employed to quantify serum selenium concentrations. Serum zinc and lipid profile indicators were measured using spectrophotometry.

Results Hypothyroidism and Hashimoto’s thyroiditis are linked to increased atherogenicity, insulin resistance, and reduced antioxidant defenses, including selenium, SePP, and zinc. Both cohorts with thyroid dysfunctions demonstrate slight elevations in depressive symptoms. Individuals with hypothyroidism and heightened depressive symptoms demonstrated augmented insulin resistance, raised atherogenic indices, and markedly reduced levels of SePP relative to those with milder depressive symptoms. Elevated levels of thyroid-stimulating hormone and atherogenic index of plasma best predicted the severity of depression in hypothyroid patients.

Conclusions The findings indicate that depression due to hypothyroidism is largely influenced by abnormalities in thyroid hormones, thyroid-stimulating hormone, metabolic pathways, and diminished antioxidant defenses. The observed results may be explained by the established impact of these hormones and biomarkers on cerebral functions, resulting in major depressive disorder.

The authors have declared no competing interest.

This study did not receive any funding

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with Iraqi and international ethical and privacy norms. The Medical Ethics Committee at the University of Kufa approved this research ethically, Reference #: MEC-96, by the International Guidelines for Human Research Protection as outlined by the Declaration of Helsinki. Informed permission was obtained from each participant prior to their inclusion in the study.

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The database created during this investigation will be provided by the corresponding author (MM) upon a reasonable request once the authors have thoroughly used the data set.