Depression is a serious mental disorder often accompanied by emotional and physiological disorders (Nguyen et al., 2017; Jackson et al., 2019). Based on the WHO data, there are more than 300 million people with depression worldwide (Puttige Ramesh et al., 2019). In the United States, 16% of people suffer depression at least once in their lifetime (Kessler et al., 2003). Depression usually occurs alongside other chronic diseases. The 15-year recurrence rate of depression in the general population is 35% (Hoen et al., 2010).

Obesity has been implicated in the development of depression (Heo et al., 2006; Rivenes et al., 2009; Luppino et al., 2010; Linde et al., 2011; Haynes et al., 2019). This is evidenced by how the outcome of depression with underlying obesity relies on treatment-seeking behavior (Felitti, 1993). Body mass index (BMI) is a reliable indicator of obesity. In addition, high BMI in adulthood has been linked with depression (Hoen et al., 2010; Mannan et al., 2016). Obesity based on BMI has been linked with the risk of developing depression (Heo et al., 2006; Rivenes et al., 2009; Luppino et al., 2010; Linde et al., 2011; Haynes et al., 2019). However, given that BMI cannot distinguish between visceral fat from fat mass, it is not an accurate measure of obesity (Huang et al., 2019; Yang S. J. et al., 2020; Favre et al., 2021). In related research, the measure of waist circumference (WC), which reflects the level of visceral fat, was found to be positively correlated with depression (Heo et al., 2006). However, just like BMI, WC does not discriminate visceral adipose tissue from abdominal subcutaneous fat (Heo et al., 2006; verson-Rose et al., 2009).

Deposition of visceral fats is associated with high circulating TNF-α and IL-6 and a decrease in insulin sensitivity (Lin et al., 2013; Yang J. et al., 2020). Visceral fats can independently predict the development of depression (Vogelzangs et al., 2008). High visceral fat at baseline, based on CT scan, has been linked with depression (Alshehri et al., 2019). Although imaging techniques such as CT and MRI can directly measure the amount of visceral fat, they cannot be routinely used due to safety and economical limitations. Currently, the visceral adiposity index (VAI) can accurately reflect the accumulation of visceral fats (Amato et al., 2010). Therefore, we explored the relationship between VAI and the development of depression using the National Health and Nutrition Examination Survey (NHANES) data for adults in the United States (US) population.

Herein, we observed a strong and stable positive correlation between VAI and the development of depression in both men and women. After controlling for confounding factors, clinically significant depressive symptoms were found to be associated with VAI. For every one-unit increase in VAI, the clinical depression increased by 14%. High VAI scores (T3) increased the highest risk of developing depression compared with the T1 group. Subgroup analysis demonstrated a strong and stable association between VAI and the development of depression.

Body mass index (BMI) has been liked with obesity and WC. In addition, it is the main clinical parameter for indirect assessment of visceral fat level. However, Yang et al. found that abdominal sagittal diameter (SAD) is a non-invasive method of measuring visceral fat content and predicts the development of depression more accurately than BMI (Zhou et al., 2020). Recent studies found that SAD and BMI cannot discriminate between subcutaneous and visceral fat mass. The VAI is based on metabolic (HDL-C and TG) and anthropometric (WC and BMI) parameters (Amato et al., 2010). Using CT scanning, Vogelzangs et al. (2008) found that the level of visceral adipose tissue is positively correlated with the likelihood of developing depression. A cross-sectional study reported that there is remarkable variation in VAI scores for any given BMI value (Du et al., 2014). We found a strong positive correlation between VAI and depressive symptoms in both men and women. The relationship between the high VAI group and depression is stronger than in the low (T1) and middle (T2) VAI groups. It also confirmed prior studies’ findings that depressive symptoms are associated with intra-abdominal fat and the ratio of visceral and total adipose area.

Depression is heterogeneous disorder (Benazzi, 2006; Du et al., 2014). Studies show that VAI reflects the deposition degree of adipose tissues and is an accurate surrogate marker for “adipose tissue function” (Numan Ahmad and Halim Haddad, 2015). In a related study, Alshehri et al. (2019) reported that the degree of obesity is positively correlated with depression. Adiposity is related to immune and metabolic dysregulations. Meanwhile, high visceral fat increases the activity of pro-inflammatory factors (Amato et al., 2010) and the development of depression (Yang J. et al., 2020). In addition, the visceral fat quality and VAI reflect the severity of coronary heart disease in patients with diabetes and coronary heart disease (Yang J. et al., 2020). In this study, we found high VAI scores strongly and positively correlated with the development of depression.

Visceral fat index (VAI) is more pathogenic than subcutaneous adiposity because of its greater endocrine activity. It is suggested that VAI is a measure of visceral fat function and a marker for cardio-metabolic disorders that is more accurate and sensitive than traditional parameters, such as WC, BMI, and blood lipid assessment (Amato et al., 2010). High visceral fat disrupts adipokinesis, which may lead to numerous metabolism-related disorders (Arai et al., 2011). Several hypotheses have been proposed to describe the relationship between intraperitoneal fat level and depression. First, high cortisol is thought to increase the risk of developing metabolic syndrome and depression (van Santen et al., 2011). Second, depression was thought to result from inflammation (Milaneschi et al., 2019). Visceral obesity is associated with levels of serum inflammatory cytokine and insulin sensitivity. Third, insulin resistance is thought to increase the risk of developing metabolic disorders, dyslipidemia, and depression (Jokela et al., 2014). Although insulin levels were not measured, a low insulin level is a risk factor for developing depression. Our findings notwithstanding, the relationship between insulin resistance, VAI, and depression needs further investigation.

Regarding strengths, first, VAI is an accurate method of estimating visceral obesity in addition to it being cheap and safe. Second, the data were large and representative of the American population. However, the self-evaluation approach without additional psychotic assessment did not reveal the specific type of depression. Third, the majority of the participants were American adults. As such, the findings of this study in the context of other ethnic groups should be interpreted with caution. Fourth, the possible interference effect of other non-traditional risk factors for depression such as inflammatory markers were not investigated. Lastly, due to the cross-sectional study, some of the risk factors, such as major cardiovascular events, were not observed. We also could not investigate the causal connection between VAI and depression as well.

VAI positively correlates with the likelihood of developing depression. As such, visceral fat must be maintained within a certain range to minimize the chances of developing depression.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by the Research Ethics Review Board of National Center for Health Statistics. The participants provided their written informed consent to participate in the study.

JL and YL provided methodological expertise and revised the article. YX, YL, and JL conceived the manuscript and drafted the manuscript. XW drafted the tables and figures. All authors read and approved the final manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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