REVIEW OF RELATED LITERATURE

Mental illnesses including depression and anxiety are leading causes of morbidity, disability and
mortality(Reference Patel, Chisholm and Parikh1,Reference Rehm and Shield2) . Dietary patterns may
influence mental health. For example, poor dietary patterns which lack essential nutrients, have a high
glycemic index and are high in added sugars may lead to adverse mental health symptoms(Reference
Rahe, Unrath and Berger3–Reference Molendijk, Molero and Ortuño Sánchez-Pedreño6). In addition, in
animal models, poor diets dysregulate brain insulin which affects mood, decreases neuronal levels of
serotonin and dopamine and increases neuroinflammation as measured by inflammatory
cytokines(Reference Kaplan, Rucklidge and Romijn7–10). Poor diets and the consumption of non-nutrient
additives in animal models can also adversely affect the intestinal microbiome which, in turn, can lead to
systemic and neuroinflammation(Reference Melo, Santos and Ferreira11) To be eligible for inclusion,
studies met the following criteria: written in English, conducted in humans of any age (clinical and general
populations); observational by design; investigated the association between ultra-processed food intake
and mental disorders; and compared different levels of ultra-processed food consumption (e.g., lower
versus higher) or ultra-processed food versus unprocessed or minimally processed food. Studies were
excluded if the NOVA food classification system was not used or if the direct consumption of ultra-
processed food was not investigated (e.g., household availability, access to, price of and purchase of ultra-
processed food).

To provide the most comprehensive overview of the relationship between ultra-processed food
consumption and mental disorders, we included studies that modelled ultra-processed food consumption
as either the exposure or outcome. In addition, we included studies where mental disorder parameters were
derived from either clinician-rated or self-reported assessments and definitions varied (e.g., presence of
common mental disorders, depressive symptoms, depressive mood, diagnosis of depression, anxiety
symptoms, anxiety-induced sleep disturbance, etc.). We aimed to synthesize these definitions and
maximize the generalizability of our findings by grouping together mental disorder categories based on the
Diagnostic and Statistical Manual of Mental Disorders—5th Edition [34], and listing whether mental disorder
diagnoses or symptoms that align with mental disorders were investigated. That is, mental disorder
categories make up the major themes of our review and results are presented as such. These themes
include the common mental disorders (e.g., depression and anxiety, which we assessed together given
their common comorbidity [35] as well as separately), trauma and stress-related disorders (e.g., post-
traumatic stress disorder and perceived stress), addiction-related disorders (e.g., food addiction and alcohol
use disorder) and eating disorders (e.g., anorexia nervosa, bulimia nervosa and binge eating disorder).
(21 JUNE 2022)

Unhealthy diets are recognized as a major determinant of the occurrence of NCDs. With the increasing
trend of NCDs, a steady rise in the share of processing foods has been seen. In the last half century food
processing has evolved greatly as a consequence of the industrialization and globalization of foods system.
Negative effects on nutritional dietary quality emerged subsequently, such as higher content in free sugar,
saturated fats, energy density and sodium, and less content in protein, fiber and micronutrients by changes
in diet patterns. It is believed that most NCDs can be reconsidering the synergistic health-related effects It
of foods, it is of great importance to study dietary patterns instead of single foods or nutrients. UPFs
consumption is increasing dominantly across the globe, especially in Western countries. It is consistent
with the increased burden of NCDs attributable to unhealthy diets. The role of some specific UPFs has
been assessed, such as processed meats and sweetened beverages, showing positive associations with
NCDs [52, 53]. In line with our findings, previous studies reported an inverse association between higher
diet quality and risk of all-cause, cardiovascular disease, and cancer mortality [54,55,56]. Adherence to
healthier diet patterns, which are characterized by a high consumption of unprocessed or minimally
processed foods, was promoted to prevent NCDs. Decrease of cardiovascular disease burden with a
healthier food system was observed in two modelling studies [57, 58]. A review of systematic reviews found
that grain products and tea were protective, while processed meats and soft drinks tended to increase the
risk [59]. Existing meta-analyses demonstrated that an optimal intake of several food groups could decrease
the risk of coronary heart disease, stroke and heart failure [60]. Overall, UPFs consumption should be
limited in prevention of Incented. (20 august 2020)

[2]. Depression etiology implies complex interactions between various factors including social,
psychological, and biological factors. Some treatments are effective but their limitations, as well as the
detrimental effect of any depressive episode on the future course of the disease, make prevention crucial
[3]. Among large-scale preventive interventions, acting on modifiable factors such as diet is a good
candidate for public health action. Large-scale epidemiological studies have consistently documented an
association between a healthy diet or dietary indexes reflecting the holistic quality of the diet and a lower
risk of depression [4,5,6,7]. For instance, in the NutriNet-Santé study, we have observed that several dietary
indexes reflecting nutritional recommendations were prospectively and inversely associated with the risk to
develop depressive symptoms [8]. On the opposite, a western dietary pattern or pro-inflammatory diet
characterized among other things by more processed foods has been associated with poor mental health
[5, 6, 9]. Previous studies that reported associations between these diets and depression considered
nutritional characteristics of the diet and interaction within the food matrix. However, some of those diets
integrate a large part of ultra-processed food (UPF) (i.e., industrial recipes that are practical, ready to eat,
and palatable [10]) which consumption has drastically increased over the past decades [11, 12]. For
instance, a recent American study reported that, between 2007 and 2012, about 60% of the overall energy
intake was provided by UPF [13]. In the French NutriNet-Santé study, UPF contributed to 35.9% of the daily
energy intake and the proportion of UPF (%UPF) in the diet has been associated with a poor overall quality
of the diet [14]. While processing ensures improvement of food availability, digestibility, short-term safety,
transportability, and storage life [15], UPF are often energy-dense; mostly very rich in fat, sugar, and salt;
and poor in micronutrients; thus, they may have a potential deleterious role on health. Beyond their
unfavorable nutritional composition, they also contain other components generated during transformation
such as neo-formed molecules produced during heating, food additives used in manufacturing, and
molecules migrated from packaging, some of which might have a detrimental role for gut microbiota [16],
involved in the development of several diseases characterized by an inflammatory component (including
depression) [17]. The investigation of the association between UPF consumption and health is therefore
important. (15 APRIL 2019)