This cross-sectional study demonstrates that when controlling for four key demographic and lifestyle factors (gender, previous psychiatric diagnosis, physical exercise frequency, and spiritual exercise frequency), a pro-inflammatory EDII score correlates to increased depressive symptoms. These findings indicate that the EDII was able to produce results commensurate with other inflammatory diet and depression studies. These results also support the growing evidence that diet modification could prove to be an important tool in the treatment of depressive symptoms.
In one of the first studies of its kind, Bergmans and Malecki used the DII to investigate the relationship between depression and inflammatory diet. They found that a high DII score is associated with two times higher odds of depression in adults [8]. Similarly, Phillips et al. found that a high DII score increased the risk for depression among adults [2]. In meta-analyses, Tolkien et al. and Wang et al. found that individuals consuming a pro-inflammatory diet were at increased risk of developing depression [28, 29]. It becomes increasingly clear that diet and depression are linked, but the relationship itself has not been determined with absolute certainty. A diet that consists mainly of sugars, trans and saturated fats, and refined carbohydrates is a common finding among those with depression, and some studies have suggested that depression itself can alter the food choices we make [17].
In recent years there has been an implication of the gut microbiome in depression. It is suggested that psychological stressors create an imbalance of bacteria, which leads to intestinal permeability, allowing bacteria to enter the bloodstream. This triggers a production of pro-inflammatory cytokines, activating the HPA axis and crossing the blood-brain barrier to produce an inflammatory response [30]. If the pathological changes come first, this could create a viscous cycle of depression fueling inflammatory diet choices, and inflammatory diet fueling depressive symptoms in turn.
It is of note that a high DII score appears to put women at increased risk for recurrent depression over a five-year period [31]. Similarly, a recent study found that a pro-inflammatory diet at baseline increased the risk for depressive symptoms over a five-year period, especially among women [7]. It is important to make the connection between these studies and Lamers et al., who observed the continued elevation of IL-6 in those with depression at six-year follow-up [13]. It appears that some individuals with chronic depression remain in a pro-inflammatory state. With diet being one of the common denominators, it is logical to investigate whether dietary intervention can mitigate the inflammatory cycle.
A recent interventional study has shown that adherence to the Mediterranean Diet for three months can lead to a reduction in depressive symptoms and improvement in quality of life [32]. These results remained consistent at six-month follow-up. Parletta et al. also measured omega-3 and omega-6 fatty acid levels in participants. They found that improvement in depressive symptoms was associated with a deceased ratio of omega-6 to omega-3 fatty acids [32]. The Mediterranean Diet is rich in docosahexaenoic acid and eicosapentaenoic acid, two omega-3 fatty acids that act on brain structure and function. They are not only considered anti-inflammatory, but they play a role in the neurotransmission of serotonin and dopamine [9]. In comparison, omega-6 fatty acids are high in the traditional processed Western Diet and are considered pro-inflammatory [32]. Perhaps unsurprisingly, the Mediterranean Diet has been shown to positively alter the gut microbiome and increase its diversity [9]. These findings suggest that implementation of an anti-inflammatory diet could be key in breaking the depression-inflammation cycle. Further study is important to determine whether an anti-inflammatory diet can prevent depression altogether.
The main strength of this study was demonstrating that the EDII can correlate to depressive symptoms. Previous dietary indexes, such as the DII, have been largely unusable to the everyday clinician. With the DII’s comprisal of forty-five different factors, most of which are nutrients, it would be quite challenging to administer and score within a standard appointment time. Even with a DII score, clinicians may not discern diet modification based on individual nutrients alone. On the contrary, the EDII was designed for simplicity of use. With the focus on sixteen pro- and anti-inflammatory food groups, the tool can be easily self-administered by the patient and results calculated in minutes. The EDII may prove to be a useful assessment tool in the treatment of depression as it requires minimal appointment time and provides a clear focus for anti-inflammatory diet changes. It could also be revisited periodically to assess for improvements in inflammatory score.
There are multiple limitations with this study. First, the entirety of this study was administered through self-reported questionnaires with potential for recall bias among participants. Second, this study did not include a twenty-four-hour recall for the EDII portion of the survey. Although the twenty-four-hour recall has its own limitations, it is commonly used in dietary studies to obtain a more accurate dietary pattern among individuals [8]. A study validating a food frequency questionnaire using two twenty-four-hour recalls found moderate to high correlations for most food groups, with only cooked vegetables and pizza showing insignificant correlation. The proportion of participants classified into the same or adjacent quartile of consumption varied from 68% in cooked vegetables to 94% in coffee [33]. Thus, food frequency questionnaires alone prove to be valid assessment tools. Third, specific medical co-morbidities and body mass index information were not included as covariates.
There should be caution in applying the results of this study to the general population. The participants were only those associated with two specific healthcare settings, including physicians, nurses, and medical students who may experience higher daily stress than the general population. It is of note that this study was conducted during the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic, potentially inflating participants’ depressive symptoms. In a recent umbrella review of meta-analyses, approximately one in four healthcare workers reported depression and anxiety during the pandemic [34]. Respondents also skewed more heavily towards female gender (n = 471 female vs. n = 157 male vs. n = 3 non-binary/other). Finally, this is a cross-sectional study, and therefore only a correlation between pro-inflammatory EDII score and depression can be interpreted. As mentioned above, reverse causation should be considered, as some studies have indicated that stress and depression may lead to pro-inflammatory food choices [5].