In the contemporary global health landscape, depression stands as a major contributor to the burden of mental illness, affecting millions of individuals worldwide (GBD 2019 Diseases and Injuries Collaborators, 2020). According to estimates by the World Health Organization (WHO), approximately 350 million people globally are grappling with the symptoms of this chronic condition that transcends physical and emotional wellbeing (GBD 2019 Diseases and Injuries Collaborators, 2020). Highlighting its significance as a prominent public health concern, the continuously rising prevalence of depressive symptoms emphasizes the necessity for comprehensive understanding of the factors contributing to its development and potential risks.

A significant body of research has pointed to an intricate relationship between depression and cardiovascular disease (CVD), two seemingly disparate conditions that share common underlying pathophysiological pathways (Carney and Freedland, 2017; Harshfield et al., 2020; Wu and Kling, 2016). Epidemiological studies consistently highlight a heightened risk of CVD events, such as myocardial infarction and stroke, among those experiencing depression (Wu and Kling, 2016).This correlation is partly explained by the shared mechanisms of inflammation, oxidative stress, and endothelial dysfunction that contribute to both depression and CVD progression (Assies et al., 2015; Manev et al., 2008; Pizzi et al., 2008). These biological processes can lead to structural changes in blood vessels and the brain, which may exacerbate depressive symptoms or promote the development of CVD (Assies et al., 2015; Manev et al., 2008; Pizzi et al., 2008).

The Atherogenic Index of Plasma (AIP), a biomarker with significant implications for predicting CVD and potentially in the context of depressive symptoms, is mathematically defined as the logarithmic ratio of triglycerides to high-density lipoprotein cholesterol (log TG/HDL-C) (Kim et al., 2022; Nunes et al., 2015). By quantifying this ratio, AIP provides valuable insights into the atherogenicity of plasma, or the likelihood of developing atherosclerosis and subsequent cardiovascular events (Dobiásová, 2004). As scientific literature increasingly implicates AIP in the incidence of cardiovascular events, it becomes imperative to explore whether this marker could also shed light on the complex interplay between CVD and mental health.

Several studies have investigated the association between AIP and CVD as well as the interconnection between CVD and depression, respectively (Hare et al., 2014; Sadeghi et al., 2021). However, there is a paucity of studies investigating the potential direct link between AIP and depressive symptoms. Notably, identifying novel biomarkers that can predict depressive symptoms would contribute to early detection and intervention, ultimately improving patient outcomes.

This study aims to address this knowledge gap by conducting a comprehensive examination of the potential association between AIP levels and depressive symptoms in US adults using data from the National Health and Nutrition Examination Survey (NHANES) spanning the years 2005 to 2018.