The role of testosterone and free triiodothyronine on suicide attempts among individuals with anxiety and mood disorders

Introduction: Thyroid hormones are implicated to depression and suicidal behavior [1, 2], while testosterone may contribute to the pathophysiology of suicidal behavior due to its direct effects on mood, cognition, and aggression [3]. However, it remains unclear how thyroid hormones interact with testosterone and how these factors link to suicidal behavior in individuals with anxiety and mood disorders. Objective: The aim of this study was to investigate the association between testosterone and free triiodothyronine concentrations and suicide attempts among individuals with anxiety and mood disorders. Methods: In this cross-sectional study we recruited 147 subjects. Among them, 101 patients were diagnosed with anxiety and mood disorders (AMD) with and without a lifetime history of suicide attempts (SA) (aged 38.8±13.1 years, 30% male) and 46 controls - individuals without a lifetime history of mental disorders or history of suicide attempts (aged 48.4±12.1 years, 34% male). All subjects were interviewed for current psychiatric diagnoses and suicidal behavior using the Mini International Neuropsychiatric Interview (MINI). Biochemical blood tests were performed to measure concentrations of free thyroxine (FT4), free triiodothyronine (FT3), thyroid stimulating hormone (TSH) and total testosterone (TT). Logistic regression analyses were used to test whether FT3 or TT levels were predictive for SA. Results: A positive correlation was found between TT and FT3 in both the control and patient groups (both p < 0.001). As a group, patient with a history of SA showed lower FT3 levels compared to those without SA and to control (5.20 ± 0.65 vs. 5.52 ± 0.62 and 5.65 ± 0.71 pmol/L, respectively; p = 0.005). The serum FT3 levels were significantly lower in female patients with a history of SA, than in females without a history of SA (p = 0.007) and compared to controls (p = 0.003). Additionally, significantly higher TT concentrations were observed in females with a history of SA compared to controls (p = 0.015). A multivariate logistic regression model was used to predict SA, incorporating age, FT3, TT, gender, and the interaction term (TT × Gender). The interaction effect, indicating a moderating role of gender in the relationship between TT and SA, was statistically significant (p = 0.028). To validate this effect, the model was re-run exclusively on female patients. Among females, lower FT3 levels were associated with an increased likelihood of suicide attempts [OR = 0.28 (95% CI: 0.10–0.79)], as were higher TT levels [OR = 12.21 (95% CI: 1.34–111.11)]. These findings suggest a gender-specific hormonal influence, with a total testosterone potentially playing a more prominent role in females. Conclusion: Lower FT3 concentrations, even within the normal reference range, and elevated total testosterone levels were associated with suicide attempts in females but not in males. These results highlight the potential value of assessing FT3 and TT levels in the clinical evaluation of suicide risk, particularly in females with mood and anxiety disorders.