Thyroid disease is characterized by abnormal morphology or dysfunction of the thyroid, such as in hyperthyroidism/thyrotoxicosis, hypothyroidism, subacute thyroiditis, autoimmune thyroiditis, thyroid nodules, and thyroid cancer (1–5). Thyroid disease is more common in women, and the impact on the health of women is greater than that of men. A decade ago, the estimated global prevalence of patients with thyroid disease reached approximately 200 million; today, the number is even greater (6). Current studies suggest that the factors associated with thyroid disease include heredity, trace elements (commonly iodine and selenium), vitamins, infection, and radiation (7–9). Some studies have shown that the emergence of thyroid diseases, especially thyroid disorders, can have a negative impact on emotional stability and aggravate existing mental illnesses (10, 11). Notably, our team has found that patients with thyroid disease tend to exhibit one or more negative emotions, such as mania, anxiety, depression, fear, and obsessive-compulsive attitudes and behaviors (unpublished work).

Borderline personality disorder, also known as emotional instability personality disorder, is a common mental disorder mainly characterized by emotion, difficulty with interpersonal relationships and self-image, and behavioral instability accompanied by various impulsive behaviors (12, 13). Notably, although borderline personality disorder is often misdiagnosed as anxiety, depression, and other mental disorders because of the unstable emotional state symptom, it is more serious than these mental disorders. Thus, we hypothesized that there might be a causal relationship between mental disorders and thyroid diseases.

Therefore, this study aimed to assess the potential causal relationship between borderline personality disorder, selected as the exposure, and non-toxic single thyroid nodules, hyperthyroidism/thyrotoxicosis, hypothyroidism and autoimmune thyroiditis, selected as outcomes, to determine whether thyroid status should be monitored in patients with borderline personality disorder.

Our study evaluated the causal relationship between borderline personality disorder and four common thyroid diseases, and the results showed that borderline personality disorder has a positive causal relationship with a single non-toxic thyroid nodule, but not with the other three thyroid diseases.

This finding contrasts with our clinical experience, which suggests that patients with hyperthyroidism and hypothyroidism tend to have more diverse psychiatric symptoms than individuals with non-toxic thyroid nodules. Previous studies have shown that individuals with non-toxic single thyroid nodules exhibit different psychiatric symptoms, primarily negative emotions (10, 11). The resultant chronic stress state can lead to changes in neurological, immune, and endocrine functions, consequently leading to changes in thyroid stimulating hormone (TSH) levels. Long-term instability of TSH levels may lead to the formation of thyroid nodules. Hyperthyroidism and hypothyroidism can induce a variety of psychiatric symptoms with differences depending on the disease. Patients with hypothyroidism are more likely to exhibit depression and anxiety, and the “mucinous edematous madness” symptom is extremely rare, while patients with hyperthyroidism are more irritable, nervous, and excited (11, 25–28). Therefore, borderline personality disorder as an exposure factor may not accurately reflect the clinical situation of various thyroid diseases. Additionally, clinical experience is subjective and sometimes not complete.

Some studies have shown that thyroid disease, especially thyroid dysfunction or autoimmune thyroid disease, is associated with negative emotions or mental illnesses; however, the nature of their relationship remains unclear (29, 30). The prevailing hypothesis suggests that thyroid diseases often manifest in varying degrees of mental disorders. Nevertheless, this hypothesis does not answer a crucial question: whether mental disorders occur before or after thyroid disease. Our study demonstrates that borderline personality disorder as a risk factor for non-toxic single thyroid nodules can precede and lead to its emergence.

In this study, we chose borderline personality disorder as the exposure variable because it is more similar to the diverse psychiatric symptoms of patients with thyroid disease and has a lower diagnostic bias than other mental illnesses. We could not include thyroid cancer as an outcome variable as intended because there is no shared SNP in borderline personality disorder and thyroid cancer.

This study has some limitations. First, although the statistics of each tool variable F was >10, it cannot completely overcome the bias caused by weak IVs. Second, although the sensitivity analysis results did not indicate the existence of multiple effects, it is difficult to rule out the potential multiple effects in MR analysis completely. Third, the patients in the GWAS database are only Europeans; hence, extending this conclusion to people of other regions is challenging and perhaps inappropriate. Fourth, the statistical methods in MR analysis are strict and conservative; consequently, the real causal relationship between exposure and outcome might have been ignored.

In conclusion, this study showed that a positive causal correlation exists between borderline personality disorder and non-toxic single thyroid nodules. Therefore, this study suggests that treatment for borderline personality disorder may reduce the risk of developing non-toxic single thyroid nodules and we should consider performing routine monitoring of thyroid status in patients with borderline personality disorder. In addition, considering the similarity of mental illnesses, we speculate that there is a causal relationship between other mental illnesses and thyroid diseases, which we will investigate in future studies.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.

QW: Conceptualization, Data curation, Writing – original draft. PL: Formal Analysis, Software, Writing – review & editing. SQ: Writing – review & editing. JY: Visualization, Writing – review & editing. ZD: Funding acquisition, Supervision, Writing – review & editing.