Nutritional psychiatry on the move: the activities of the <scp>ECNP</scp> Nutrition Network to leverage nutrition for brain health

Brain health is a pressing global concern1. Neurodevelopmental and mental disorders are leading causes of disability. As the population continues to grow and age, the number of individuals affected by dementia worldwide is expected to rise significantly. While evidence-based interventions for mental disorders are available, challenges persist, particularly as not all patients respond to current pharmacological or psychological treatments. Our limited understanding of psychiatric conditions and their treatment stems from major gaps in knowledge of the underlying neurobiological mechanisms. Emerging research suggests that the pathophysiological underpinnings of mental disorders can extend beyond the central nervous system. Compelling evidence indicates that disorders such as major depression should be viewed as whole-body conditions that entail both central processes, such as changes in neurotransmitter systems and reduced neuroplasticity, and peripheral factors resulting from the involvement of the immune and neuroendocrine systems. Immune activation interacts with metabolic and endocrine systems that control energy homeostasis, as shown by significant associations between inflammatory markers (C-reactive protein, interleukin-6) and higher body mass index, fat mass, triglycerides, as well as lower HDL cholesterol in large-scale studies. Thus, metabolic and immune dysregulation are intertwined, prompting research to explore biomarkers of this combined dysregulation2. We are beginning to recognize that nutrition might help close the prevention and treatment gap in mental disorders. Poor diet quality is a major environmental risk factor for brain disorders and one of the few that are modifiable3. While evidence continues to grow on the impact of nutrition across the life course, we are still far from fully harnessing its potential to improve mental health conditions. The field of nutritional psychiatry has recently gained momentum, driven by a surge in observational and intervention studies supporting a role for diet in managing psychiatric symptoms4. At the same time, epidemiological research highlights unhealthy eating as a growing risk factor for metabolic and brain health. Additionally, data indicate that obesity and metabolic conditions deriving from the use of medications, such as antipsychotics, present challenges for clinicians, reinforcing the need for an approach to mental disorders that considers brain and body health as a unique integrated system. Individual nutrient needs are shaped by physical and psychological health, habitual diet and lifestyle, and differ across the life course and in response to environmental factors. One of the main challenges that nutritional psychiatry currently faces is the lack of conclusive evidence that diet and nutrition impact mental health. Overall, randomized controlled trials (RCTs) investigating dietary change in treatment of mental disorders remain limited, although some report significant improvements in mood and reduced anxiety in adults5. Not all studies reproduced these findings, underscoring the need to replicate, refine and scale-up dietary intervention research for prevention and treatment. The Nutrition Network of the European College of Neuropsychopharmacology (ECNP) was established with the main mission to better understand the bidirectional links between mental health and nutrition, including the mediating systems, to inform novel neuropsychological and neuropharmacological interventions4, 6. The Network fosters interdisciplinary research and strengthens connections with relevant stakeholders across Europe, including health and food policy makers. Founded in 2016 by researchers at the intersection of nutrition and mental health, it brings together experts from academia and industry, mainly neuroscientists, nutritionists, psychiatrists, psychologists and geneticists. The Network’s key areas of expertise include gut-brain signalling (hormones, vagal afferents, gut microbiota, inflammatory signals), neuroendocrine regulation, metabolites/nutrients, and the relevant neural systems (revealed through genetics, epidemiology, functional brain imaging, behavioral models in rodents, and morphological, biochemical and molecular neuroscience tools). The Network’s main areas of action include: a) identifying new strategies (dietary, lifestyle, pharmacotherapy) to improve mental health in individuals with mood and other mental disorders; b) exploring neural substrates and pathways linking diet to psychological constructs such as mood and neurocognition (e.g. impulsivity, reward sensitivity); c) investigating afferent signaling systems (hormones, genes, immune modulators, gut microbiota) connecting diet to these psychological constructs; d) clarifying interactions between diet and pharmacotherapy (including side effects) for mental health and metabolic diseases, combining dietary advice with pharmacotherapy to enhance efficacy; e) providing evidence to support dietary policies and guidelines for mental health improvement and for treatment of eating disorders; f) establishing strong collaborations with health and food policy makers, patient advocacy groups, and pharmaceutical and food industry stakeholders. One of the key achievements of the Network to date has been its participation, as the BRAINFOOD cluster, in the European Union-funded EBRA (European Brain Research Agenda) project. EBRA was established as a catalyst for brain research, bringing together stakeholders, researchers, clinicians, patients, governments, funders and public institutions to streamline and better coordinate brain research across Europe while fostering global initiatives. In 2021 and 2022, expert and policy meetings were held with relevant stakeholders, culminating in a position paper emphasizing the need for public investments to unlock the full potential of nutrition for brain health. A core principle of EBRA is that all relevant stakeholders – clinicians, patient advocates, and public and private research institutions – must collaborate in a coordinated, non-fragmented manner to identify knowledge gaps and research strategies that will drive meaningful progress in improving brain health through nutrition. Our Network has taken on the role of coordinating research and policy in nutrition and mental health, identifying the most urgent research priorities in this field. Although dietary interventions appear to influence mood through various mechanisms, including the gut microbiome, inflammatory modulation, oxidative stress reduction, and hypothalamic-pituitary-adrenal axis regulation7, 8, more extensive RCTs are necessary to establish clear causal relationships, and to address the current variation in how diet interventions are implemented. Health care professionals and policy makers should prioritize food and nutrition education9, since significant misunderstandings persist among both the general public and health professionals regarding the role of nutrition in brain health, exacerbated by misleading and exaggerated messages in popular media. Given the vast potential of nutrition to support brain health, we advocate for greater research investment to strengthen the relevant evidence base, increasing awareness among health professionals and the public, so that this critical topic becomes a priority in policy agendas4, 9.