Anxiety disorders are among the most common psychiatric conditions worldwide, affecting up to 4.4% of the global population according to the World Health Organization. Anxiety disorders are defined by persistent and disproportionate fear, excessive worry, and sustained hypervigilance, which collectively impair daily functioning and reduce quality of life. Epidemiological data indicate that anxiety onset commonly occurs during adolescence or early adulthood, exhibiting a high prevalence in women (Remes et al., 2016). Accordingly, anxiety substantially affects socioeconomic stability, driven by reduced productivity, increased healthcare use, and high rates of comorbidity with depression and other chronic medical disorders (Kalin, 2020; Stein et al., 2017).

Although the biological traits underlying anxiety disorders remain incompletely understood, clinical and preclinical evidence suggest that neuroendocrine dysregulation, immune activation, mitochondrial dysfunction, and alterations in lipid metabolism might contribute to pathophysiology (Grogans et al., 2023; Mishra and Varma, 2023). Based on this context, elevated circulating levels of IL-6, TNF-α, and IL-1β have been reported in Chinese individuals diagnosed with generalized anxiety disorder compared with healthy controls, reflecting heightened immune system activation (Tang et al., 2018). IL-6 concentrations also positively correlate with Hamilton Anxiety Rating Scale (HAM-A) scores in anxious Chinese patients (Zou et al., 2020). Beyond primary psychiatric cohorts, increased IL-6, TNF-α, and IL-17A levels have been observed in Chinese patients with rheumatoid arthritis presenting comorbid anxiety symptoms (Liu et al., 2012). Consistent with these findings, IL-17A concentrations positively correlate with State-Trait Anxiety Inventory scores in postpartum women with depression and anxiety of an Asian cohort (Min et al., 2022), and also, TNF-α and IL-17A levels in Chinese individuals with coronary artery disease are associated with higher Hospital Anxiety and Depression Scale scores (Lu et al., 2022). Furthermore, the MCP1 chemokine has been linked to anxiety in pregnant Mexican women during the third trimester (Camacho-Arroyo et al., 2021) and in patients with alcohol use disorder in clinical psychiatric patients from Pakistan (Kazmi et al., 2022). Collectively, these data indicate that systemic immune activation, reflected by altered cytokine and chemokine profiles, may contribute to the pathophysiology of anxiety disorders and underscore the potential relevance of immunological biomarkers in clinical assessment and therapeutic strategies.

Moreover, evidence supporting the role of systemic inflammation in anxiety has prompted the exploration of novel anti-inflammatory interventions. Approaches that modulate peripheral inflammation range from dietary interventions designed to lower the dietary inflammatory index (Pang et al., 2025) to microbiome-directed treatments such as probiotics, prebiotics, and fecal microbiota transplantation (Peirce and Alviña, 2019; Adıgüzel et al., 2025). These lines of work motivate translational efforts to evaluate whether attenuating systemic inflammation can ameliorate anxiety in defined patient subgroups. Such strategies emphasize the potential relevance of immunological and metabolic biomarkers in clinical assessment and novel therapeutic designs. In parallel, accumulating evidence suggests that lipid metabolism might contribute to the pathophysiology of anxiety disorders. Individuals with depressive and anxious symptoms showed increased concentrations of ceramide species C20:0 and C22:0, together with elevated sphingomyelinase activity, and reduced levels of phosphatidylcholine PC O-36:4 and sphingomyelin SPM 23:1 inversely correlate with depression and anxiety scores in participants from the Netherlands (Demirkan et al., 2013). Also, Alzheimer’s individuals showing anxiety as a comorbidity, reported elevated C14:0, C16:0, C18:0, and C24:1 circulating ceramides compared with cognitively normal individuals without anxiety in a clinical cohort from China (Xing et al., 2016). Similarly, anxious patients diagnosed with Parkinson’s disease showed accumulation of C14:0, C16:0, C18:0, and C24:1 ceramides, whereas a major decrease in fatty acyls, glycerolipids, sterol lipids, and other sphingolipids species relative to both healthy controls without anxiety in a clinical cohort from China (Dong et al., 2021). These observations indicate that alterations in plasma sphingolipid profiles are consistently reported with the manifestation and severity of anxiety symptoms across independent worldwide clinical cohorts.

Therefore, understanding how lipid metabolism interacts with inflammatory pathways could provide novel insights into the molecular basis of anxiety disorders. The current study aimed to determine whether alterations in plasma lipid species are associated with inflammatory profiles and the severity of anxiety symptoms in a Mexican cohort. We aimed to enrich the comprehension of a potential lipid–immune axis contributing to the pathophysiology of anxiety and anxiety-related phenotypes.

Neurobiological traits that predispose individuals to anxiety have been proposed in several reports. In this study, we enriched the characterization of inflammatory and lipidomic signatures in Mexicans individuals according to their anxiety symptom severity. We found that individuals with clinical anxiety exhibited elevated plasma levels of IL-6, MCP-1, and TNF-α, together with reduced IL-17A, supporting the presence of a pro-inflammatory systemic profile. In parallel, exploratory lipidomic analyses suggested a trend toward lower circulating levels of DG 18:2/22:4, DG 18:2/22:6, LPC 24:1, and TG 60:11 (FA 22:5) in the anxiety group, although these associations were not sustained after multiple testing correction. Regression analyses confirmed group-specific associations of MCP-1 and TNF-α with anxiety in the clinical group. These findings support the existence of a pro-inflammatory molecular profile in Mexicans individuals diagnosed with anxiety.

Both clinical and preclinical studies have consistently shown that anxiety disorders are associated with altered levels of circulating inflammatory mediators. Several studies have reported increased concentrations of IL-6, TNF-α and IL-1β in individuals with generalized anxiety disorder compared to healthy controls, suggesting a possible role for peripheral immune activation (Tang et al., 2018). Among these, IL-6 has emerged as a particularly robust marker. For example, elevated IL-6 levels correlate with Hamilton Anxiety Scale scores in Chinese clinical cohorts (Zou et al., 2020) and display weak to moderate positive correlations with Hamilton scores in individuals with atopic dermatitis (Yang et al., 2025). Similarly, patients with rheumatoid arthritis and comorbid anxiety show increased levels of IL-6, TNF-α and IL-17A (Liu et al., 2012). TNF-α and IL-17A have also been positively associated with anxiety scores in Chinese patients with coronary artery disease (Lu et al., 2022) and postpartum women with anxiety and depression (Min et al., 2022). More recently, a case–control study conducted in Bangladesh reported that serum IL-17A concentrations were higher in patients with generalized anxiety disorder and correlated positively with symptom severity (Roknuzzaman et al., 2024). It is important to note that several reports analyze populations with pre-existing inflammatory comorbidities. These underlying conditions often involve a high degree of systemic immune activation, which may differ from the inflammatory profiles observed in our cohort. Moreover, methodological and analytical factors can strongly affect IL-17A measurements. IL-17A is a low-abundance analyte and shows high assay variability across platforms; several validation studies note poor precision for IL-17A in multiplex and ELISA formats, especially near the lower limit of detection. In contrast, IL-17A is relatively stable to delay processing in common anticoagulants, but differences in kit sensitivity, sample dilution and calibration can still produce discrepant results between studies (Surenaud et al., 2016; Nakamizo et al., 2024). Together, these technical issues argue for caution when interpreting single-study differences in IL-17A.

Conversely, studies in Middle Eastern populations have reported lower IL-6 and TGF-β1 levels in GAD patients compared to controls, and a negative association between IL-6 and GAD-7 scores (Alfi et al., 2025). In Mexican cohorts, MCP-1 has been linked to anxiety scores during late pregnancy (Camacho-Arroyo et al., 2021), while elevated MCP-1 levels have also been observed in anxious patients with alcohol use disorder from South Asian populations (Kazmi et al., 2022). More recently, increased serum CCL5 concentrations have been documented in Indian patients with generalized anxiety disorder (Suresh et al., 2025).

Our findings align with these reports by confirming higher levels of IL-6, MCP-1, and TNF-α in Mexican individuals diagnosed with anxiety. Specifically, we observed that MCP-1 and TNF-α were positively associated with anxiety severity, supporting their relevance as pro-inflammatory markers at the clinical threshold. These results reinforce the growing body of literature linking peripheral inflammation to anxiety symptoms. Nevertheless, cross-study variability in inflammatory profiles likely reflects differences in sample characteristics, comorbid conditions, and methodological approaches.

In the current study, targeted lipidomic analysis identified selective, nominal alterations in glycerolipids and lysophospholipids, whereas no group-level changes were observed in sphingolipids such as ceramides, dihydroceramides, hexosylceramides, or lactosylceramides. Specifically, individuals with anxiety exhibited lower levels of diacylglycerol species DG 18:2/22:4 and DG 18:2/22:6, decreased lysophosphatidylcholine 24:1, and reduced TG 60:11 (FA 22:5). Notably, these exploratory findings did not withstand multiple comparison correction; however, they point toward specific lipid signatures that contrast with previous reports across diverse clinical populations. For example, Demirkan et al. (2013) observed lower concentrations of PC O-36:4 and a reduced sphingomyelin C23:1/SPM C16:0 ratio, both negatively associated with anxiety scores in a large Dutch cohort. Altered levels of lysophospholipids have also been described: LPC 16:0 and LPE 18:0 were elevated in anxiety patients compared to controls (Kui et al., 2022). Moreover, early studies reported increased plasma triglyceride concentrations in anxiety and anxiety–depression groups (Pistorio et al., 2011), and serum triglycerides were found to correlate with STAI-T scores in both anxiety and comorbid depression samples (Hu et al., 2018; Wang et al., 2016). A metabolomic study of Parkinson’s disease patients with comorbid anxiety identified reduced levels of several diacylglycerols and sphingolipid-related species, as well as oxidized lipid derivatives, compared to patients without anxiety (Dong et al., 2021). These discrepancies underscore the biological heterogeneity of anxiety disorders and suggest that lipidomic profiles may be highly sensitive to cohort-specific factors such as age, ethnicity, and metabolic state. Together, these studies highlight the potential contribution of altered lipid metabolism to anxiety pathophysiology. Rather than definitive markers, our findings provide a hypothesis-generating framework to further explore the lipid–immune axis.

Mechanistically, interactions between lipid signaling and inflammation may provide new insights into the biological basis of anxiety disorders. For instance, glucocorticoid signaling and phospholipase activation, both relevant to stress responses, can modulate PC/PE ratios, phosphatidic acid, DG and TAG pools (Zorkina et al., 2024). These pathways link psychological stress to circulating lipid signatures. Nonetheless, the direction and magnitude of lipid alterations vary across studies, likely reflecting differences in cohort characteristics, comorbidities, medication use and the analytical strategies (Wei et al., 2019). Several factors may help explain discrepancies between our results and prior reports, including differences in age, nutritional status, body composition, comorbid conditions and medication exposure (Demirkan et al., 2013; Dong et al., 2021; Kui et al., 2022). Moreover, the targeted nature of our lipidomic approach may have missed species reported in untargeted analyses. Importantly, our sample included young, physically healthy participants and excluded individuals receiving psychotropic treatment, which may have uncovered an early-stage or distinct metabolic signature compared to older or clinically complex cohorts.

Finally, we did not find significant correlations between individual lipid species and the composite anxiety severity scores, and regression models combining lipids and cytokines also failed to identify independent predictors. This lack of association may be partly explained by the limited sample size and by the multidimensional nature of anxiety, in which distinct symptom domains (e.g., somatic, cognitive, or affective components) may relate differentially to metabolic alterations. In this context, group-level lipid differences may reflect state-dependent metabolic shifts or biologically defined subgroups rather than linear scaling with overall symptom severity. Future studies with larger cohorts and dimensional symptom assessments will be necessary to determine whether specific lipid signatures associate with particular anxiety phenotypes or clinical subdomains.

The present study examined the interplay between lipidomic alterations and pro-inflammatory signatures in relation to anxiety symptomatology in a Mexican cohort of young adults. We identified MCP-1 and TNF-α as inflammatory markers showing group-specific associations restricted to individuals with clinically diagnosed anxiety. In parallel, targeted lipidomic analyses revealed selective reductions in specific glycerolipid and lysophospholipid species, including diacylglycerols, lysophosphatidylcholine, and triglycerides. Although these lipid alterations did not scale linearly with anxiety severity, they may reflect state-dependent metabolic changes or biologically distinct subgroups within anxiety phenotypes. Consequently, these lipidomic signatures represent preliminary insights that warrant further targeted investigation to define their clinical relevance. Elucidating whether these molecular shifts represent causal mechanisms, compensatory responses, or biomarkers of vulnerability will require larger, longitudinal, and multimodal studies. Future investigations integrating lipid flux analyses, expanded metabolomic profiling, and comprehensive immune phenotyping may help clarify the role of lipid–immune interactions in anxiety and identify biomarkers or therapeutic targets that complement current clinical approaches.