Work Packages

The Eat2beNICE project is funded by the EU and is professionally organized into 10 different workgroups, called Work Packages (WP), which are staffed by highly experienced professionals, researchers, PhDs and MDs to bring this project to fruition by 2022. The details about the organization and distribution of responsibilities are listed in the table below:

• WP1

  Exploiting existing epidemiologic data sets to generate new knowledge on the effect of nutrition on impulsive, compulsive and aggressive/antisocial behaviour
  Lead beneficiary: UMCG

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  The aim of WP1 is to identify (combinations of) nutritional and lifestyle components that significantly affect the variation in impulsivity (i.e., emotional, cognitive, and behavioural) and compulsivity (repetitive behaviour, diminished ability to delay/inhibit thoughts or  behaviours and addictions). In this, we will consider different food cultures of most relevance to Europe. WP1 will study how individual-specific factors (age, gender, Socio-Economic Status (SES)) moderate such relationships. We will determine how nutritional/lifestyle  effects are modified/modulated by the genetic make-up (using twin modelling) identifying the molecular-genetic pathways involved.

  Objectives:

  1) To determine the dietary components and lifestyles related to impulsivity and compulsivity and their societal consequences (i.e. addiction and antisocial behaviours) including the effects of sex and SES.

  Specific aims:

  • To identify, which dietary components and lifestyle factors are associated with harmful or protective effects on impulsivity and compulsivity, stratified by developmental period n Swedish, Dutch, Norwegian, and United Kingdom samples
  • To determine dietary components and lifestyle factors that, when combined, strengthen harmful or protective behavioural effects or cancel each other out, stratified by developmental period

  2) To determine the extent to which effects of specific dietary components and lifestyles on impulsivity and compulsivity depend on a person’s genetic background.

  Specific aims:

  • To estimate the heritability of impulsivity and compulsivity conditional on lifestyle and food components by twin modelling
  • To determine gene-environment interactions relevant to impulsivity and compulsivity through gene, gene-set, and genome-wide approaches, conditional on nutritional and lifestyle components D
• WP2

  Nutritional interventions
  Lead beneficiary: KAR

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  WP2 will determine the effect of four nutritional interventions on reducing impulsivity, compulsivity, and antisocial behaviour/aggression on the short and long term in four comprehensive clinical trials.

  These interventions are:

  • Restrictive elimination diet (versus WHO health guidelines diet)
  • Broad spectrum supplementation
  • Probiotics
  • Mediterranean diet

  The interventions will cover much of the lifespan; we will test separate age groups, fitting the intervention such that they are most relevant (i.e. no prior studies available) and/or they are most appropriate for the characteristics of the age group (e.g., using easy  upplements in adolescents, which are notoriously treatment-incompliant). Participants (male and females) with high levels of impulsive behaviour, as defined by an >85th percentile score on the primary outcome UPPS-P scale (Urgency, Premeditation, Perseverance,   Sensation seeking, and Positive urgency) will be recruited amongst others through psychiatric hospitals.

  Objectives:

  1. To determine the short- and long-term effects of a personalized elimination diet (ED) versus a standardized diet according to WHO health guidelines on reducing impulsive, compulsive, and aggressive behaviour in children
  2. To determine the double-blind placebo controlled (10 weeks) and open label (10 weeks) effects of broad-spectrum supplementation on reducing impulsive, compulsive and aggressive behaviour in adolescents
  3. To determine the double-blind placebo controlled (10 weeks) and open label (10 weeks) effects of probiotics on reducing impulsive, compulsive and aggressive behaviour in adults
  4. To determine the short- and long-term effects of an energy-restricted Mediterranean diet with physical activity promotion and behavioural treatment versus an unrestricted caloric Mediterranean diet following usual care on reducing impulsive, compulsive, and  aggressive behaviour in adults/elderly with overweight (55-75 y)
  5. To identify demographic (gender, age, socio-economic status) and clinical predictors and mediators of response to nutritional interventions from data collected in all four clinical trials
• WP3

  Effects of physical activity and exercise in interaction with diet
  Lead beneficiary : GUF

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  It is well known that exercise and physical activity (PA), key lifestyle factors, have a major influence on impulsive and compulsive behaviours. Also, exercise interacts with dietary patterns and might even counteract negative effects of certain types of nutrition. Mechanisms behind these phenomena, especially regarding mental health, are largely unknown. Furthermore, there are few, if any, large studies that investigate the interaction of reliably measured PA and diet on impulsive and compulsive behaviours. WP3 will capitalize on the extension of three already funded studies to address these issues. To do so, we implement objective measures to monitor activity and behaviour (mHealth devices, accelerometers). Biomarker assessments will shed light on the mechanisms underlying effects of PA and exercise on impulsive/compulsive disorders and traits.

  Objectives:

  1. To investigate whether exercise and PA interact with diet to modify impulsive disorders and behaviours and whether other factors moderate or meditate effects of PA
  2. To study how exercise/PA influence the human gut microbiome and thereby the gut-brain-axis
  3. To test the hypothesis that PA and exercise, in interaction with diet, can buffer against stress and thereby contribute to resilience
  4. To generate insight into the (epi)genetic architecture that might orchestrate such interactions
• WP4

  Public health aspects, policy recommendations, and dissemination
  Lead beneficiary: UiB

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  Dissemination of our research findings is essential to induce changes in lifestyle and reduce impulsivity and compulsive behaviours of individuals in the general population as well as in groups at particularly high risk. For research results to change society, we need innovative ideas, going beyond what scientists are currently used to doing. The main goal of WP4 is therefore to use diverse and novel routes to disseminate evidenced-based information about nutrition, lifestyle, and modifiable behavioural factors to prevent maladaptation or reduce its consequences.

  Objectives:

  1. To develop content and strategies for dissemination of evidence-based information about the links of nutrition and lifestyle with behaviour to reach different target audiences, including the different sections of the general public, relevant patient groups, clinicians,  scientific networks, such as the European College of Neuropsychopharmacology (ECNP) and policy makers
  2. To translate findings from WP1, WP2, and WP5 into food solutions. We will create evidence-based food solutions for limiting impulsivity and reducing compulsive behaviour in novel ways, by working together with a celebrity chef. Together with him, we will be able to reach the most relevant sections of the general public as well as the food and supplement industries
  3. To train junior investigators in science dissemination through courses and involvement in the planning and implementation of our dissemination activities, which enables us to reach multiple countries and language groups
  4. To make Eat2beNICE known to the scientific community and the general public
• WP5

  Intestinal microbiota as a mechanistic link between nutrition/lifestyle and impulsivity and compulsivity
  Lead beneficiary: RUMC

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  The relationship between the bacterial communities in the gut (the microbiome) and the brain is bi-directional, the brain alters the gut microbiome, and the gut microbiome also modulates brain function. The main goal of WP5 is to understand the communication from the gut microbiome to the brain and its effects on behaviour. Studies conducted over the last decade in rodents show that gut microbiota can modulate brain development, neurotransmitter systems, signaling pathways, and synaptic proteins, converging in observable  behavioural changes. In humans, the microbiome may provide an important link between our genes and the exposure to diet (through nutrients and metabolites), that influence susceptibility to maladaptive behaviour and psychiatric disorders. Immune, neural, and/or entero-endocrine processes, as well as soluble factors and/or metabolites of commensal bacteria may enable the gut microbiome to influence the brain in utero and during and after birth. However, the specific effects on behaviour as well as the pathways and mechanisms underlying communication between the gut microbiome and the brain are poorly understood in humans.

  Objectives:

  1. To understand how diet in infancy (i.e. breastfeeding and solids) is related to the development of impulsive and compulsive behaviour, and how this process is mediated by the intestinal microbiota
  2. To understand the role of the gut-microbiota as a mechanistic link between diet/exercise and impulsive/compulsive behaviour in childhood, adolescence and adulthood
• WP6

  Effects of nutrition, lifestyle, and microbiota on the brain
  Lead beneficiary: RUMC

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  Nutrition, lifestyle, and microbiota may affect impulsivity, compulsivity, and aggression/antisocial behaviour, but it is unclear, whether they also affect the fronto-striatal and fronto-amygdalar brain systems that are involved in rational and emotional control processing,  and whether effects on these brain systems mediate effects on behaviour. It is also unclear whether (epi)genetic determinants mediate and/or moderate behavioural and neural effects of nutrition, lifestyle and microbiota.

  The overall aim of WP6 is to test the hypothesis that amelioration and prevention of impulsivity, compulsivity, and aggression/antisocial behaviour is mediated by effects on the brain substrates of cognitive control, reward processing, and emotion regulation, and study whether (epi)genetic variation interacts with nutrition and the microbiome to influence neural correlates.

  Objectives:

  1. Cost-effective mining of existing cohorts with data on nutrition, lifestyle, and microbiota, as well as with extensive MRI data and data on impulsivity, compulsivity, and/or antisocial behaviour
  2. To acquire MRI and microbiota data in two intervention studies described in WP2 (elimination diet, and broad-spectrum supplementation in high-impulsive adolescents), and examine effects of these interventions on brain measures, together with WP2 and WP5
  3. To examine in the intervention studies the links between effects on behaviour and the brain and moderation/mediation by microbiota and epigenetics, together with WP5 and WP7
  4. To examine effects of physical activity on brain measures in an RCT that examines the effects of physical activity on impulsivity
• WP7

  Epigenetic modification profiles for impulsivity and compulsivity
  Lead beneficiary: UKW

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  The overall goal of this WP is to investigate gene-by-environment (GxE) and gene-by-intervention (GxI) interactions and epigenetic regulation of genes relevant to impulsive and compulsive behaviours as well as addiction risk in both humans and model animals displaying enhanced impulsive/compulsive and addiction-related traits/behaviours.

  WP7 provides (i) a strong translational axis for epigenetic modification profiling of human impulsive, compulsive and addictive behaviours in a genetic and neurobiological context, (ii) a platform for the elucidation of epigenetic brain mechanisms in mice aimed at  amelioration and prevention of impulsive, compulsive, and addictive behaviour by nutrition, lifestyle, and/or microbiome components, and (iii) is strongly aligned with the core objectives of WP1-3 and WP6.

  Objectives:

  1. To identify and replicate GxE-moderated and epigenetically regulated candidate genes for impulsive, compulsive, and addictive behaviour in pre-existing selected human cohorts
  2. To investigate and validate epigenetic programming by nutrition, lifestyle, and/or microbiome components impacting neurobehavioural characteristics of human impulsive/compulsive behaviour and addiction risk
  3. To translate and validate novel epigenetically regulated genes associated with increased impulsivity/ compulsivity and addiction risk in gene-by-intervention (GxI) mouse models that exhibits enhanced impulsive, compulsive and/or addiction-related traits/behaviours
  4. To use results of 1-3 to determine the utility of observed gene regulation components as biomarkers for the effects of preventive strategies and therapies using nutrition, lifestyle, and/or microbiome components in ameliorating impulsive/compulsive and addictive  behaviour
• WP8

  Ethics and Training
  Lead beneficiary: RUMC

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  Eat2beNICE strives to accomplish the largest possible societal and scientific impact. This is to be achieved by combining the effective use of existing datasets, samples, and models with newly collected cohorts. These plans bring with them important responsibilities, both in  terms of ethical conduct as well as in the training of early career researchers.

  Objectives:

  1. To ensure ethical conduct of human and animal studies in Eat2beNICE
  2. To standardize data collection procedures and analyses through training and review
  3. To educate a new generation of scientists, who are capable of understanding and integrating research across different levels of investigation, from molecule to man and population. In addition, the scientists should learn how to effectively communicate their findings to  different types of audience (in collaboration with WP4).

  To enable such education, we will have the early career researchers develop portfolio’s with their training needs and wishes, establish mentorships, and offer different training modules, including master classes and e-learning.

• WP9

  Project management and implementation
  Lead beneficiary: RUMC

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  Effective project management is a central element of successful research. This is because large research projects entail a lot of administrative work.

  Objectives:

  1. To make Eat2beNICE achieve its objectives and to deliver in time, budget and quality its milestones and deliverables
  2. To establish a within-project communication infrastructure which enables the partners to communicate efficiently between them and to stay connected for the run-time of the project
  3. To help the consortium abide by the regulations and contractual obligations according to the grant agreement, its annexes and the consortium agreement
  4. To preserve the rights of the partners regarding intellectual property and to act as a mediator in case of disputes
  5. To look after the project`s finances and assist in the reporting process to the European Commission
• WP10

  Work package title Ethics requirements
  Lead beneficiary: RUMC

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  The objective is to ensure compliance with the ‘ethics requirements’ set out in this work package.