A total of 548 patients diagnosed with hypothyroidism in Wuxue First People’s Hospital, in Hubei Province from January 2018 to September 2022 were enrolled, including 177 males and 372 females; The average age was 60.11 ± 15.78 years old, ranging from 18 to 97 years old. Inclusion criteria: 1) Patients with clinical diagnosis of hypothyroidism; 2) Patients were newly diagnosed and had not been treated with any antidepressant, antihypertensive, cardiovascular drugs, and thyroid drugs (including levothyroxine, etc.); 3) All study subjects participated voluntarily and oral informed consent was obtained. Exclusion criteria: 1) Patients unable to cooperate with the investigation due to critical illness such as disturbance of consciousness or cardiac function grade IV; 2) Patients with severe mental illness or cognitive impairment.

The gender, age, comorbidities (such as depression, hypertension, diabetes, dyslipidemia, acute myocardial infarction and so on), free triiodothyronine (FT₃), free tetraiodothyronine (FT₄), and thyroid stimulating hormone (TSH) levels were recorded.

Thyroid function was detected by direct chemiluminescence method. Fasting venous blood was collected in the morning to detect FT₃, FT₄ and TSH. The reference ranges of FT₃, FT₄ and TSH were 3.53 - 7.37 pmol/L, 7.98 - 16.02 pmol/L and 0.56 - 5.91 mU/mL, respectively.

SPSS 22.0 was used for data statistical analysis. The measurement data in line with normal distribution were expressed as mean ± standard deviation, and the measurement data of non-normal distribution were expressed as M (P25, P75). The non-parametric rank sum test was used for comparison between the two groups. Chi-square test was used for comparison between groups. Because depression scores did not follow the normal distribution, Spearman rank correlation was used to analyze hypertensive patients with hypothyroidism. Multivariate binary Logistic regression was used to analyze the influencing factors of hypertension in patients with hypothyroidism. A difference of 0.05 was considered statistically significant.

There were 234 patients (42.7%) in hypothyroidism without depression group (group A) and 314 patients (57.3%) in hypothyroidism with depression group (group B). There was no significant difference in age, gender, FT₄ level, and the number of diabetes between the two groups (P < 0.05). The TSH level, the number of hypertension, coronary heart disease, and hyperlipidemia in group B were statistically significantly higher than those in group A (P < 0.05). The FT₃ level in group B was statistically significantly lower than that in group A (P < 0.05), as shown in Table 1 , Table 2 .

Spearman rank correlation analysis showed that hypertension was positively correlated with depression (r_s = 0.092), coronary heart disease (r_s = 0.000), hyperlipidemia (r_s = 0.000), diabetes (r_s = 0.000), and age (r_s = 0.000) (P < 0.05). It was negatively correlated with FT₃ (r_s = 0.000) (P < 0.05), but not with gender (r_s = 0.011), TSH (r_s = 0.051) and FT₄ (r_s = 0.014) (P > 0.05), as shown in Table 3 .

Multivariate binary logistic regression analysis showed that coronary heart disease, hyperlipidemia, FT₃ and FT₄ were the influencing factors of hypertension. The risk of hypertension in patients with coronary heart disease and hyperlipidemia significantly increased by 3.425 and 1.761 times (P < 0.01), respectively. With the decrease of FT₃, the risk of hypertension increased (P < 0.01); with the increase of FT₄, the risk of hypertension increased (P < 0.01). See Table 4 , Figure 1 .

a: Actual observations of Pearson Chi-square values.

*: P < 0.05, **: P < 0.01.

OR: Odds Ratio, B: Beta.

The mechanism of interaction between thyroid disease, depression and anxiety is not completely clear. The latest studies have shown that the hypothalamic-pituitary-thyroid (HPT) axis plays a role in depression and anxiety disorders, and its mechanism may be related to the TSH level in patients, and there is a negative correlation between them [10] . The main feature of subclinical hypothyroidism is that TSH is elevated, while FT₃ and FT₄ are normal. Compared with ordinary patients with anxiety and depression, it is more difficult for patients with subclinical hypothyroidism to relieve anxiety and depression under the treatment of anti-anxiety and depression drugs. Studies have shown that escitalopram oxalate combined with levothyroxine sodium can improve the anxiety and depression of patients with subclinical hypothyroidism and anxiety and depression, and its efficacy is better than that of single medication. The mechanism may be related to the enhancement of central serotonin activity, the reduction of TSH, and the improvement of FT₃ and FT₄ levels [13] . Escitalopram oxalate combined with levothyroxine sodium provides a new reference for the treatment of anxiety and depression in patients with subclinical hypothyroidism and anxiety and depression. Reducing thyroid hormone levels in patients with hyperthyroidism can effectively relieve the clinical symptoms of patients, but anxiety and other negative emotions of patients are often difficult to eliminate. Studies have found [15] that paroxetine combined with I³¹¹ can effectively relieve anxiety and depression in patients with hyperthyroidism and emotional disorders, improve the treatment effect of hyperthyroidism, and improve the levels of TSH, FT₄ and FT₃ in patients. Escitalopram combined with quetiapine has strong neurotransmitter antagonism, which can greatly reduce the impact of HPT dysfunction on patients, so as to alleviate thyroid dysfunction [16] . Studies have shown that compared with the control group, the serum TSH and FT₃ levels of the observation group were significantly increased, while the serum FT₄ level was significantly decreased after treatment, indicating that escitalopram combined with quetiapine can improve the thyroid function of patients and reduce the negative emotional symptoms of patients [17] . The incidence of hypertension with depression is high, and the treatment is more difficult than that of simple hypertension, and depression patients generally have thyroid hormone disorders. Studies have shown that felodipine sustained-release tablets combined with escitalopram oxalate tablets have good efficacy in the treatment of hypertension with depression, and can effectively correct thyroid hormone disorders, control blood pressure, reduce depressive symptoms, and have good safety [18] . High serum FT₃ level and comorbidity of thyroid disease may increase the risk of readmission after hospitalization for major depressive disorder (MDD). Routine assessment and intervention of thyroid function during depression treatment is necessary to prevent re-hospitalization [19] . Studies have shown that the clinical use of T₃ can be used as an antidepressant enhancer in patients with major depression who do not respond to antidepressant monotherapy. Thyroid hormone-based antidepressants are recommended as a treatment option in cases where monotherapy fails, and clinicians also recommend the use of thyroid hormone supplements in unresponsive depressed patients, especially those with TSH levels in the high normal range [20] . In addition to its use as augmentation, evidence from multiple randomized controlled trials also supports the use of T₃ for accelerating the antidepressant response to tricyclic antidepressants (TCA).

Thyroid disease is often accompanied by psychiatric disorders, and even cardiovascular and endocrine diseases such as hypertension and diabetes. At present, there is still a lack of research on the combination of thyroid disease and depression complications. In the future, more extensive research on the combination of hyperthyroidism, hypothyroidism, subclinical hypothyroidism, subclinical hyperthyroidism and depression, anxiety, dissociation and other mental disorders can be carried out.

Some researchers analyzed the correlation between HAMD (Hamilton Depression Scale), HAMA (Hamilton Anxiety Scale) cores and thyroid function in female patients [21] and found that T₄ level was correlated with HAMA total score (P < 0.05), TSH level was associated with HAMD total score (P < 0.05). FT₃ and FT₄ levels were positively correlated with HAMA and HAMD scores (P < 0.01). FT₃ and FT₄ levels are more sensitive in female patients with depressive episode, and their changes are closely related to the severity of the disease. For women at different stages, some researchers have explored the relationship between hypothyroidism during pregnancy [22] and postpartum anxiety and depression, and found that the occurrence of postpartum anxiety and depression symptoms was correlated with hypothyroidism during pregnancy. Based on the study of anxiety and depression in menopausal women with diabetes and subclinical hypothyroidism, it has been shown that the course of diabetes is a risk factor for anxiety, and the level of TSH is a risk factor for depression [23] . Postmenopausal women with type 2 diabetes mellitus complicated with subclinical hypothyroidism (SCH) often have anxiety and depression, especially those with longer duration of diabetes and higher TSH level. Psychological care should be given in time.

Depression and anxiety disorders in women are highly prevalent diseases, which are significantly higher than those in men, and are often accompanied by thyroid function diseases. Most of the current research is focused on female patients, and the correlation between depression and thyroid function in women can be subdivided into different stages such as menstruation, pregnancy, pregnancy, menopause, old age, etc.