Suicide ideation represents a significant global public health concern, with depression being one of its primary contributing factors. According to the World Health Organization (WHO), approximately 800,000 individuals die by suicide annually, corresponding to a global mortality rate of 11.4 per 100,000 population, with suicide accounting for 1% of all deaths worldwide (1). The prevalence of depression, a major risk factor for suicide ideation, exhibits significant variation across diverse populations and regions. Global epidemiological data indicate that depression affects approximately 300 million people, with a worldwide prevalence of 4.4% (2). In the United States, the lifetime prevalence of depression is estimated at 16% (3), while in China, the prevalence of depressive symptoms among middle-aged and elderly adults reaches 35.19% (3, 4).

Recent epidemiological studies have yielded comprehensive insights into the prevalence of suicidal behaviors. A systematic review of the European general population revealed annual prevalence rates of 3.6%, 1.6%, and 0.5% for suicidal thoughts, plans, and attempts, respectively (5). These findings are corroborated by regional studies, such as one conducted in Andalusia, which reported point prevalence rates of 2.4% for suicidal ideation, 1.1% for suicide plans, and 0.6% for suicide attempts (5).

Beyond epidemiological data, understanding the underlying mechanisms is crucial. The relationship between adiposity and mental health outcomes, including suicide ideation, likely involves both biological and psychological pathways. From a biological perspective, visceral adipose tissue functions as an active endocrine organ that secretes pro-inflammatory cytokines which may induce neuroinflammation and affect neurotransmitter systems implicated in mood regulation (6–8). Visceral adiposity is also associated with insulin resistance and hypothalamic-pituitary-adrenal axis dysregulation, potentially affecting brain regions involved in emotional processing (7). Psychologically, individuals with obesity often experience weight stigma, discrimination, and reduced quality of life, which may contribute to depressive symptoms and, in some cases, suicidal thoughts (9, 10).

Emerging research indicates that insulin resistance, frequently observed with visceral obesity, leads to chronically elevated fasting blood glucose (FBG). Elevated FBG can disrupt neuronal energy metabolism, increase oxidative stress, and promote neuroinflammation—factors known to impair emotion regulation and contribute to increased risk of depression and suicidal behavior (11). Chronic hyperglycemia has also been associated with hippocampal and cortical dysfunction in neuroimaging studies (12), providing a plausible mechanistic link between metabolic syndrome and psychiatric outcomes. Consequently, FBG may function as a pivotal metabolic mediator, establishing a connection between visceral adiposity and suicidal ideation.

The Visceral Adiposity Index (VAI) has emerged as a novel biological indicator for assessing visceral fat accumulation and associated metabolic risks. Unlike traditional anthropometric measures such as the Body Mass Index (BMI), the VAI offers distinct advantages in evaluating fat distribution, particularly visceral adiposity, by incorporating multiple parameters including waist circumference, weight, height, and biochemical indicators. Recent research has demonstrated significant associations between VAI and various health conditions, including type 2 diabetes (13), cardiovascular diseases (14), and depression (15). Furthermore, VAI has shown superior predictive capability compared to BMI in discriminating different types of adiposity and associated health risks.

However, the relationship between VAI and suicide ideation remains largely unexplored. While extant research has identified associations between VAI and certain psychological parameters, such as impulsive behaviors in severely obese individuals, the specific mechanisms and extent of these relationships require further investigation (16). Earlier studies have indicated that individuals with BMI ≥25 demonstrate higher proportions of suicide ideation, suggesting a potential link between adiposity measures and suicide risk (17). Furthermore, the established role of VAI as a predictor of cardiovascular disease and metabolic syndrome suggests the possibility of indirect effects on suicide ideation through its impact on quality of life and psychological well-being.

The present study aims to investigate the potential relationship between visceral adiposity, as measured by VAI, and suicidal ideation, with particular focus on identifying any non-linear patterns or threshold effects. Additionally, we explore the potential mediating role of fasting blood glucose and examine effect modification by demographic and clinical subgroups. Using data from the National Health and Nutrition Examination Survey (NHANES), this research seeks to enhance our understanding of how metabolic factors may influence mental health outcomes, potentially informing more comprehensive approaches to suicide risk assessment.

This cross-sectional study examined the relationship between VAI and suicidal ideation using a nationally representative sample of 11,931 NHANES participants. The findings revealed a significant non-linear association with a threshold effect at VAI=6.81, below which each unit increase in VAI was associated with 9.4% higher odds of suicidal ideation (OR=1.094, 95% CI: 1.028–1.163, P=0.005). This relationship was particularly pronounced among older adults (≥60 years), females, and individuals with comorbidities such as hypertension or diabetes.

Our findings align with and extend previous research on visceral adiposity and mental health outcomes. Kim et al. (24) demonstrated in a Korean population (n=7,238) that higher VAI levels were significantly associated with depressive symptoms, with each 1 cm² increase in visceral fat associated with a 1.006-fold increase in depression risk, particularly among women. However, our study advances this field by: (1) examining the more severe outcome of suicidal ideation rather than depressive symptoms alone; (2) utilizing a larger, more diverse U.S. population; and (3) identifying a critical threshold effect that reveals the non-linear nature of this relationship. Supporting evidence indicates that elevated triglyceride levels significantly increase depression and suicidal tendencies risk, while low HDL-C levels correlate with higher suicide attempt likelihood (25–27), consistent with our VAI-based findings.

The observed association likely operates through multiple interconnected pathways. Visceral adipose tissue secretes pro-inflammatory cytokines (TNF-α, IL-6) while reducing adiponectin, potentially triggering neuroinflammation and disrupting serotonergic systems critical for mood regulation (28, 29). Additionally, VAT-associated insulin resistance may affect emotional regulation through neuroinflammation and HPA axis dysregulation (30).

The pronounced gender differences observed align with prior research showing VAT’s stronger association with depressive symptoms in middle-aged women (31, 32). This may reflect hormonal influences unique to women, including menopause-related changes that affect emotional regulation (33, 34). Neuroimaging studies demonstrate that women with high VAI exhibit reduced gray matter density in the ventral anterior cingulate cortex, potentially impairing emotional and cognitive regulation (16).

VAI offers significant advantages over conventional visceral fat measurement methods (CT/MRI) as a cost-effective, clinically practical mathematical model based on readily available anthropometric and biochemical parameters (35). Unlike traditional obesity metrics (BMI, waist circumference), VAI specifically reflects metabolic dysfunction and adipose tissue endocrine function (28). The identification of VAI=6.81 as a threshold value holds significant clinical relevance, enabling improved risk stratification with distinct management strategies. For individuals with VAI <6.81, the linear relationship (9.4% increased suicidal ideation risk per unit) supports proactive interventions including lifestyle modification, metabolic health optimization, and routine mental health screening integration into metabolic assessments. For individuals with VAI ≥6.81, where the association plateaus, more intensive evaluation is warranted through coordinated metabolic-psychiatric management and integrated care pathways.

Our mediation analysis revealed that FBG accounts for 31.74% of the VAI-suicidal ideation association, indicating substantial but incomplete mediation. While the wide confidence interval (4.43%–181.74%) reflects cross-sectional analysis limitations, the point estimate provides valuable clinical insight into metabolic mechanisms connecting visceral adiposity to mental health outcomes. The remaining 68.26% suggests multiple parallel pathways: inflammatory mechanisms involving cytokine-mediated neuroinflammation; lipid metabolism disruption affecting neuronal membrane composition and neurotransmitter function; HPA axis dysregulation increasing psychiatric vulnerability through altered cortisol secretion; and psychosocial factors including weight stigma and reduced quality of life. Additionally, behavioral clustering of risk factors (smoking, alcohol use, physical inactivity) among high-VAI individuals may contribute through non-glucose-mediated pathways.

It is imperative to acknowledge the limitations of this study. Firstly, as a cross-sectional investigation, it is only possible to establish associations between VAI and suicidal ideation without inferring causality. Furthermore, the absence of longitudinal data precludes examination of temporal relationships between VAI changes and the development of suicidal ideation. Secondly, VAI, while it is practical as an anthropometric surrogate, may introduce measurement bias compared to gold-standard imaging methods (CT/MRI), which could potentially attenuate observed associations. Furthermore, the assessment of suicidal ideation was predominantly based on self-reported questionnaires, as opposed to the utilization of structured clinical interviews, a practice that has the potential to engender recall bias. Thirdly, although the analysis employed representative NHANES data, it should be noted that the findings may not be generalizable to populations with different racial compositions, dietary patterns, or lifestyle factors. Despite adjustments being made for a number of confounding variables, unmeasured variables such as genetic predisposition, family psychiatric history, and psychological stress sources remain unaccounted for. Fourthly, the present mediation analysis demonstrates inherent limitations due to its cross-sectional design, with wide confidence intervals (4.43%–181.74%) reflecting statistical uncertainty when temporal precedence cannot be established. The relatively low prevalence of suicidal ideation (8.4%) and the absence of multiple comparison corrections in exploratory subgroup analyses may contribute to instability in the estimation process and to inflation of Type I error. In conclusion, it is evident that the development of prospective longitudinal designs incorporating validated imaging-based adiposity measures, in conjunction with appropriate statistical corrections, is imperative to address the identified methodological limitations.

This cross-sectional study identified a non-linear association between VAI and suicidal ideation, with a threshold at 6.81, which was partially mediated by fasting blood glucose (31.74%). The association was found to be more pronounced among older adults and individuals diagnosed with diabetes or hypertension.

In view of the limitations inherent in cross-sectional designs, these findings indicate associations rather than causality and should be regarded as preliminary evidence requiring prospective validation. Nevertheless, the results of the study highlight the potential value of considering metabolic parameters in mental health assessment. It is evident that further longitudinal studies employing imaging-based adiposity measures are required in order to elucidate the underlying causal mechanisms and to ascertain whether metabolic interventions have the potential to complement psychological approaches in the context of suicide prevention.