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SYNOPSIS: In a meta-analysis of 42 studies, researchers found that subjects who reported following the Mediterranean diet closely had a 0.67 reduced risk of developing depressive symptoms compared with low adherence to this diet.
SOURCE: Lassale C, Batty GD, Baghdadli A, et al. Healthy dietary indices and risk of depressive outcomes: A systematic review and meta-analysis of observational studies. Mol Psychiatry 2018; Nov 21. doi: 10.1038/s41380-018-0299-7. [Epub ahead of print].
Lassale et al noted mixed results from the literature regarding diet and depressive symptoms. Citing several factors, such as variable methodology both when defining diet and measuring depressive symptoms that could be contributing to these mixed results, they conducted this meta-analysis to pool and analyze results from studies using specified dietary indices and a standardized approach to measuring depressive symptoms.
More than 300 million people worldwide live with depression. The prevalence varies worldwide and generally is higher in more developed countries. Debilitation from untreated or unresponsive depressive disorders contribute to an estimated productivity loss to the global economy of $1 trillion per year.1,2 In 2016, an estimated 16.2 million U.S. adults had at least one depressive episode, and the prevalence among adult women and men was 8.5% and 4.8%, respectively. Children also are affected, but at a lower rate. Sadness, apathy, somatic symptoms, poor concentration, and sleep disturbance are among the symptoms of this often chronic psychiatric disorder.3
To be included in this comprehensive review and meta-analysis, depression had to be documented by a clinician or study staff or measured by a validated scale or questionnaire. Even within these parameters, the measurement of depression varied among the 42 studies, with methods ranging from self-reported physician diagnosis to antidepressant use to 10 different scales, including Beck Depression Inventory (BDI), Geriatric Depression Scale (GDS), and Moods and Feelings Questionnaire (MFQ). All longitudinal studies excluded subjects with depressive symptoms or depressive disorder at the start of the study.
Dietary indices reflect compliance with specified dietary patterns; thus, a dietary index gives a composite measure of diet quality. Lassale et al found few studies comparing dietary indices between various healthy diets so they conducted a separate meta-analysis for each dietary pattern. In each meta-analysis, the group compared depressive symptoms in highest to lowest adherence to the diet. Longitudinal studies were given extra weight over cross-sectional studies because of the concern that the relationship between diet and depressive symptoms is not a one-way street — mood may influence diet just as easily as diet can affect mood. Every study used food frequency questionnaires to monitor and record dietary compliance and adherence. Most of the studies included information about diet at one point in time rather than on a continuum, although the frequency differed depending on study length. Below are brief descriptions of each diet and/or dietary index and results of meta-analysis.
Mediterranean Diet: four dietary indices; six longitudinal and three cross-sectional studies
In general, this well-known diet emphasizes green leafy vegetables, fruits, whole grains, fish, nuts, and beans, with olive oil as the principal source of fat.4 Across the studies, four different indices were used to measure adherence to this diet: the original Mediterranean Diet score (MDS), the relative Mediterranean Diet Score (rMDS), the alternative Mediterranean Diet Score (aMDS), and the Mediterranean Style Dietary Pattern Score (MSDPS). Each index includes slightly different foods and different cutoff scores to measure degree of adherence to the specified diet.
Results from four longitudinal studies (36,556 respondents) were analyzed to estimate the relative risk of developing depressive symptoms when comparing high to low adherence to this diet. A relative risk of 0.67 (95% confidence interval [CI], 0.55-0.82) was calculated for this group. (See Table 1.) Two additional longitudinal studies were not included because of incompatible methodology. Results of the three cross-sectional studies were not consistent.
Healthy Eating Index (HEI); three dietary indices; three longitudinal and four cross-sectional studies
The HEI measures diet quality in accordance with recommendations of the Dietary Guidelines for Americans. These guidelines shape federal nutrition standards and policies for relevant national programs. The three indices used were the original AHEI, the AHEI-2005, or the AHEI-2010. Each includes slightly different components and score ranges.5
Results from three longitudinal studies (45,533 respondents) were analyzed to estimate the relative risk of developing depressive symptoms when comparing high to low adherence to this diet. A relative risk of 0.76 (95% CI, 0.57-1.02) was calculated for this group, but concerns about significant heterogeneity limit the usefulness of these results. (See Table 2.)
Dietary Inflammatory Index (DII); one index; five longitudinal and four cross-sectional studies
The DII is based on an algorithm calculating the inflammatory potential of foods. The raw score often is converted into a “grade” reflecting level of inflammation. The DII is based on the understanding that inflammation plays a role in many chronic conditions and that inflammation on a vascular level can be modified by diet. Extensive literature searches calculating the inflammatory potential (and anti-inflammatory potential) of numerous food items led to the development of this index. Forty-five food “parameters,” including macronutrients and micronutrients, as well as some whole foods such as ginger and garlic, are scored according to inflammatory potential, with a range of -10 to 10. Higher scores reflect greater inflammatory potential.6,7
Results from five longitudinal studies (31,416 respondents) were analyzed to estimate the relative risk of developing depressive symptoms when comparing the least inflammatory to the most inflammatory diets. A relative risk of 0.76 (95% CI, 0.63-0.92) was calculated for this group. However, Lassale et al noted significant heterogeneity possibly because of gender differences. Three of these studies found no relationship between DII and depressive symptoms in men, while one study found the association only in men and not in women. (See Table 3.)
Dietary Approaches to Stop Hypertension (DASH); one index; one longitudinal study and three cross-sectional studies
The DASH plan, developed to combat hypertension or prehypertension with or without pharmacologic intervention, is rich in vegetables, fruits, low-fat dairy, and whole grains. In general, high-sodium foods, fatty foods, and foods or beverages with high sugar content are avoided.8 The DASH diet score or a modified version of the same was used in all studies. In the only longitudinal study, the Fung DASH diet score was compared to modified versions. There was an inverse association with depression only when using the Fung DASH dietary index. Given these results and the limited number of studies, no conclusions were drawn about an association with depressive symptom reduction.
Depression can be relatively easy to recognize but more difficult to treat. The Diagnostic and Statistical Manual of Mental Disorders defines eight subtypes of depression, including major depressive disorder, depressive disorder due to another medical condition, premenstrual dysphoric disorder, and unspecified depressive disorder. There are clear and specific diagnostic criteria for each. Central to all depressive disorders is a functional impairment due to change in mood.9 However, each subtype presents under different circumstances and may require nuanced intervention. In the pooled results covered by the meta-analysis, the subtypes were not specified nor was there a consistent distinction between clinical depression and depressive symptoms. These two factors alone may contribute to the heterogeneity and may have skewed the results. Clarification in future studies should assist in developing more compelling, generalizable conclusions.
The first-line treatment for most forms of depressive disorders is conventional medication combined with specific psychotherapies. However, compliance with these interventions tends to be limited and variable. Psychotherapy can be difficult to access. Financial barriers, geographical barriers, the time commitment, and stigma may discourage some from seeking this potentially powerful intervention.
Antidepressants are not always well accepted either. Authors of a study of 367 people with depression found that more than 50% of the group discontinued antidepressants within the first six months of treatment. Additionally, more than 60% of those who stopped taking antidepressants did so without consulting a physician.10 Even under optimal conditions, investigators have noted that conventional treatment is effective in only one in three cases of depressive disorder, making prevention a priority for intervention.11
Clinicians working with depressed patients often become aware that a barrier to implementation of any intervention is the lower energy, more negativity, and decreased motivation that accompanies this disorder. The authors of the studies in this meta-analysis pointed to diet as a potential preventive agent for treating depression. Reducing or preventing symptoms before full-blown clinical depression emerges is a major goal in the treatment of depression and could alter the course of the disorder in a positive direction.11
Notably, Lassale et al did not address dietary intervention in patients with clinical depression at the onset of the study. Although certainly there is suggestive evidence of a link, rigorous studies with standardized diagnostic criteria are needed before clinicians can draw conclusions regarding this population.
In a January 2019 guest editorial published in the Psychiatric Annals, Dr. Louisa Sylvia noted that despite the promise of integrative modalities in treating depression, interventions such as “exercise, yoga, nutrition, and mindfulness” tend to be neglected, with at most 30% of providers prescribing any one of these for a patient. Her thought is that clinician acceptance and use of these modalities may increase with clear evidence of efficacy.12
This meta-analysis regarding dietary index and the risk of depressive outcomes is a step forward toward synthesizing evidence for the efficacy of nutritional intervention in depression. Although the limitations cannot be overlooked, Lassale et al showed clear observational evidence of a link toward reduced risk of depressive symptoms or clinical depression with adherence to a Mediterranean diet and/or avoidance of a pro-inflammatory diet.
Perhaps the limitations of the reviewed studies are as important as the positive findings. That is, emerging from this review is a mandate for future studies in this field to be prospective and long-term to control for reverse causality. Additionally, establishing a gold-standard measurement to determine severity of depressive symptoms, distinguish between depressive symptoms and full-blown clinical diagnosis, and move away from food frequency questionnaires toward a more precise instrument to quantify diet over time will help these studies gain legitimacy and validity. The proposed mechanism of dietary intervention for depression revolves around the theory that diet can lead to oxidative stress and inflammation, both of which cause neuronal damage. Foods with antioxidant and anti-inflammatory characteristics, such as fruit, vegetables, and nuts, can reduce or reverse this damage. Recent work points to the microbiota-gut-brain axis, an intimate connection between gut microbials and the brain. It is thought that modification of gut microbiota via diet can alter neurotransmission and influence neuropsychiatric disorders such as depression.13
While research in the field continues, there is no need to delay implementing results of this meta-analysis into clinical practice. There are no drawbacks or downsides to recommending healthy dietary interventions such as the Mediterranean diet and/or avoiding pro-inflammatory foods when discussing depression or prevention of this disorder. On the other hand, the clear potential benefits in reducing the burden of depression or avoiding this disorder altogether by incorporating diet change into treatment is compelling. Patients experiencing severe depression may find it difficult to muster the energy needed to plan and modify a diet. Catching such patients (those at risk for depressive episodes) at early stages may help lower this barrier. Providers should discuss diet with patients and help them adopt such an intervention into an overall treatment and wellness plan.
Financial Disclosure: Integrative Medicine Alert’s Executive Editor David Kiefer, MD; Peer Reviewer Suhani Bora, MD; Relias Media Executive Editor Leslie Coplin; Editor Jonathan Springston; and Editorial Group Manager Terrey L. Hatcher report no financial relationships relevant to this field of study.