According to the World Health Organization (2021), approximately 20 million individuals attempt suicide annually, and over 700,000 individuals die by suicide each year (Yang et al., 2022). Among these, 90 % suffer from a mental illness, with 40 % to 70 % explicitly experiencing major depressive disorder (MDD) (Dong et al., 2018). Patients with MDD and suicidal ideation (SI) are at an increased risk for comorbidities, medication challenges, reduced quality of life, increased healthcare needs, and substantial social burdens (Borentain et al., 2020; Benson et al., 2021). Given these severe implications, early detection of SI is crucial to prevent the progression of suicidal behaviors and mitigate societal impacts.

SI involves contemplating, planning, or considering suicide and represents an early stage in the progression towards suicidal behavior (Klonsky et al., 2016). Identifying SI early is critical for evaluating suicide risk, and understanding its biological underpinnings is a crucial step in improving early intervention strategies. However, while progress has been made in understanding suicide risk, the precise biological mechanisms driving SI in MDD remain unclear, warranting further investigation.

Emerging evidence indicates that thyroid dysfunction, a common feature among suicidal depressed patients, may play a critical role in SI (Duval et al., 2017; Luo et al., 2024; Yang et al., 2023). Studies have shown that altered thyroid function, including low or blunted levels of thyroid-stimulating hormone (TSH), is associated with SI in MDD patients, potentially due to a disrupted hypothalamic-pituitary-thyroid (HPT) axis feedback mechanism (Jokinen et al., 2008; Kim et al., 2013). The compensatory mechanism hypothesis posits that thyroid dysfunction observed in MDD and SI may result from an altered feedback loop within the HPT axis (Duval et al., 2010). Under normal physiological conditions, thyroid hormones (THs), specifically triiodothyronine (T3) and thyroxine (T4), modulate TSH secretion via a negative feedback mechanism (Ortiga-Carvalho et al., 2016). In affected individuals, however, this regulatory loop is disrupted, characterized by hyperactive thyrotropin-releasing hormone (TRH) secretion and an attenuated TSH response (Gary et al., 2003). Consequently, this leads to reduced levels of TSH and thyroid hormones, despite elevated TRH concentrations (Duval et al., 2022). However, further empirical validation of this hypothesis is required.

Thyroid dysfunction may influence brain regions involved in mood regulation and cognitive control, which are critical for the development of SI (Bauer et al., 2008; Zhao et al., 2023a). Neuroimaging studies have indicated associations between brain abnormalities and SI in MDD patients. For example, decreased orbitofrontal-thalamic connectivity has been linked to impaired decision-making processes associated with SI (Kim et al., 2017), while reduced gray matter volume in the middle frontal gyrus has been suggested as a potential biomarker for suicidal behavior (Wang et al., 2020). Furthermore, deficits in cognitive inhibition, especially in areas such as the inferior frontal gyrus and thalamus, may contribute to the development of depressive states and facilitate suicidal acts (Richard-Devantoy et al., 2016). These findings underscore the complexity of the neural correlates of SI in MDD and highlight the need for further research into the relationship between these factors.

The brain operates as a dynamic system with constantly shifting functional patterns that reflect changes in mental states (Deco et al., 2011; Hutchison et al., 2013). Recent studies suggest that brain dynamics, particularly in executive and emotional processing regions, can vary significantly in MDD patients with SI (Yang et al., 2022; Li et al., 2019; Li et al., 2022a; Li et al., 2022b). These dynamic alterations may serve as potential biomarkers for suicide risk and could improve clinical predictive models.

This study aims to explore differences in thyroid function between MDD patients with and without SI and to examine variations in brain dynamic activity, particularly the dynamic amplitude of low-frequency fluctuations (dALFF), between these groups. The research seeks to identify potential biomarkers for early detection and intervention in SI by investigating the relationship between thyroid dysfunction and brain dynamics. Specifically, we hypothesize that MDD patients with SI will exhibit distinct thyroid profiles and brain dynamics compared to those without SI, which may help advance our understanding of the biological underpinnings of suicide risk.