AMBROSIAC - A Menu for Brain Responses Opposing Stress-Induced Alterations in Cognition

Lead Research Organisation: King's College London
Department Name: Psychological Medicine

Abstract

Diet and nutritional habits significantly impact on brain fitness, mental and cognitive health throughout life. The relative abundance of specific dietary nutrients, depending on intake, bioavailability and metabolism, affects mental health and cognitive ability via direct and indirect mechanisms that modulate neuronal function and synaptic plasticity. Optimum nutrition is a key determinant in the well-being of the healthy ageing population world-wide, as ageing is characterized by a decline in metabolism and homeostatic processes as well as age-related cognitive impairment over time, leading to functional decline and increased risk for disease. Chronic stress has been shown to negatively impact brain plasticity and cognitive performance, in particular in the ageing brain. Interestingly, the aged brain resembles the stressed brain on both behavioural and cellular levels and stress-induced cognitive alterations are likely to be more marked in the elderly. Likewise, poor nutritional habits are hypothesized to correlate with a heightened stress reactivity and susceptibility and greater cognitive decline in elderly, supporting the notion that interactions between nutritional factors and stress susceptibility represent critical determinants of cognitive performance and age-related cognitive decline.

Technical Summary

This proposal investigates how diet through stress-related mechanisms affects cognition across the lifespan using preclinical and clinical approaches. Particular focus will be on the influence of nutrition on increased susceptibility for stress-induced cognitive deficits in memory and executive functioning from adulthood to old age (aim 1) and the impact of a nutritional intervention on cognitive ability, stress vulnerability and stress perception (aim 2). Next, the molecular mechanisms by which targeted nutritional interventions can improve stress-induced vulnerabilities in cognition will be investigated using preclinical models (aim 3). Throughout the 3 aims, the gut microbiota will be investigated as a novel critical signalling mediator between nutritional intake, stress susceptibility and maintenance of cognitive health in ageing (using samples from aims 1, 2 and 3). Elucidating the cellular and molecular mechanisms and pathways through which nutrition can promote the resistance of neurons to insults and enhance mental fitness will help us to determine how best to modulate diet composition in order to attenuate stress vulnerability, reduce susceptibility to metabolic disorders, and ultimately promote brain health during healthy ageing.

Planned Impact

In line with the vision of the JPI to strengthen Europe's competiveness, AMBROSIAC aims to positively impact population health, society and the economy though influencing industry (food, pharma, biotechnology) via the project outcomes. AMBROSIAC will provide a platform to uncover the interactions between diet and targeted nutritional interventions with stress vulnerability and cognitive performance throughout life. The cooperation between several of the partners of the AMBROSIAC project is already existent, as collaborative efforts have already been initiated in the context of different research projects investigating the relationship between metabolic, nutritional and inflammatory processes and mental health, including the relationship between stress and cognition.

Publications

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Barnes J (2017) Genetic Contributions of Inflammation to Depression. in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

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Caraci F (2017) A new nomenclature for classifying psychotropic drugs. in British journal of clinical pharmacology

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Cattaneo A (2018) Integrating 'Omics' Approaches to Prioritize New Pathogenetic Mechanisms for Mental Disorders. in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

 
Title For all sad words 
Description Developed in collaboration with Prof Carmine Pariante, this work is a metaphorical blood exchange. It draws from Prof Pariante's research at King's College on blood inflammation in patients with depression, Stanford University's studies that show transfusion of young blood in old mice reversed aging, and Lund University's proposition that a protein found in beetroot (incidentally an anti-inflammatory food) could substitute human blood. The artist, Lynn Lu, invited participants to tell her about a significant personal regret. Then she pricked their finger and place a drop of blood in a petri dish. In exchange, she offers them a shot of anti-inflammatory beet juice. Over the weekend, the petri dishes fill with blood "inflamed" with lament, while vials of detoxifying beetroot empty one by one. 
Type Of Art Performance (Music, Dance, Drama, etc) 
Year Produced 2017 
Impact Engagement with the Science Gallery and other artistic organisation interested in using art to disseminate science 
URL https://lynnlu.info/for-of-all-sad-words-of-tongue-and-pen-the-saddest-are-these-it-might-have-been/...
 
Description Biomedical Research Centre - Affective Disorder and Interface with Medicine Theme
Amount £50,000,000 (GBP)
Funding ID NIHR Biomedical Research Centre at the South London and Maudsley NHS Trust and King's College London 
Organisation National Institute for Health Research 
Department NIHR Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 04/2017 
End 03/2022
 
Description Distinguished Investigator Award
Amount $100,000 (USD)
Organisation Brain & Behaviour Research Foundation 
Sector Charity/Non Profit
Country United States
Start 07/2018 
End 06/2019
 
Description NIHR Senior Investigator
Amount £45,000 (GBP)
Funding ID NF-SI-0616-10074 
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 04/2017 
End 03/2020
 
Description The Impact of Early Adversity on Trajectories of Brain Maturation and Mental Health in Young Adolescents
Amount £100,144 (GBP)
Funding ID MR/S003444/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2018 
End 09/2022
 
Description Understanding the role of gender, inflammation and sex hormones in the prevention and treatment of affective disorders Psychiatry Research Trust
Amount £83,444 (GBP)
Funding ID Psychiatry Research Trust 
Organisation King's College London 
Department Psychiatry Research Trust
Sector Charity/Non Profit
Country United Kingdom
Start 10/2018 
End 09/2021
 
Description Antidepressants may not be perfect, but they DO save lives: Expert reveals how life-changing the drug can be when used in the right way 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact Professor Carmine Pariante has treated thousands of patients with depression Despite expert claims the pills have devastating side-effects, he stands by them
They work when used correctly, especially alongside psychological therapy

Read more: http://www.dailymail.co.uk/health/article-4243156/Antidepressants-not-perfect-save-lives.html#ixzz4awYvDP2Q
Year(s) Of Engagement Activity 2017
URL http://www.dailymail.co.uk/health/article-4243156/Antidepressants-not-perfect-save-lives.html
 
Description Article for The Independent 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact An opinion piece defending the safe use of antidepressants. As a psychiatrist, I know that Johann Hari is wrong to cast doubt on antidepressants
Suggesting that prescribing antidepressants to a patient who suffers from clinical depression is the equivalent of treating them as a 'machine with malfunctioning parts' is wrong, unhelpful and even dangerous

Carmine Pariante Wednesday 10 January 2018 14:00 GMT
Year(s) Of Engagement Activity 2018
URL http://www.independent.co.uk/voices/johann-hari-depression-anti-depressants-psychiatrists-pills-ther...
 
Description Blog on the Huffington Post 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A regular blog entry that I have on the Huffington Post on topics of mental health
Year(s) Of Engagement Activity 2012,2015,2016,2017
URL http://www.huffingtonpost.co.uk/author/carmine-pariante
 
Description Inspire the Mind - a new online publication on mental health 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact InSPIre the Mind is new online publication on the Medium Platform, directed by Carmine Pariante. It will bring the point of view of a group of clinicians and researchers working in mental health. In this new publication, we want to complement people's accounts by discussing the clinical and the scientific evidence underpinning these personal experiences, while also sharing with the readers our research, our clinical work, and or our cultural and societal considerations. We are the members of the Stress, Psychiatry and Immunology (SPI) Lab at the Institute of Psychiatry, Psychology and Neuroscience, at King' College London, and these are our stories.
Year(s) Of Engagement Activity 2019
URL https://medium.com/inspire-the-mind
 
Description Interview for BBC Radio 4 Programme 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Media (as a channel to the public)
Results and Impact BBC health reporter James Gallagher explores the increasing body of evidence that a dysfunctional immune system is responsible for the depression or psychotic illness experienced by hundreds of thousands, perhaps millions, of people in the UK. James talks to the psychiatrists investigating this new understanding of mental illness and to people who may benefit from treatments aimed at the immune systems rather than their brain cells.

"I believe this is one of the strongest discoveries in psychiatry in the last twenty years", says Professor Carmine Pariante of his and other research on the immune system and depression. "It allows us to understand depression no longer as just a disorder of the mind and not even a disorder of the brain, but a disorder of the whole body. It shifts conceptually what we understand about depression."

James also talks to New York journalist Susannah Cahalan. She began to experience paranoid delusions and florid hallucinations when her immune system made damaging antibodies against part of the molecular circuitry in her brain. Treatment to eliminate the antibodies prevented her committal to psychiatric hospital. Psychiatrist Professor Belinda Lennox at the University of Oxford says she has evidence that a significant proportion of people presenting for the first time with psychotic symptoms are victims of a similar autoimmune problem.

Producer: Rachael Buchanan and Andrew Luck-Baker.
Year(s) Of Engagement Activity 2016
URL http://www.bbc.co.uk/programmes/b07pj2pw
 
Description Plenary Lecture at the Conference of Forensic Psychiatry of the Royal College of Psychiatrists 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A plenary lecture on my research on depression and inflammation
Year(s) Of Engagement Activity 2017
 
Description Plenary Lecture at the Italian Society for Psychopathology 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A plenary lecture on my research on depression and the immune system
Year(s) Of Engagement Activity 2017
 
Description Visit of HRH The Duchess of Cambridge to Professor Pariante's laboratory 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The Duchess of Cambridge visits King's College London's IoPPN and the Mother and Baby Unit at Bethlem Royal Hospital

The Duchess of Cambridge visited Professor Pariante's laboratory at the Maurice Wohl Clinical Neuroscience Institute at King's College London to find out more about the Institute of Psychiatry, Psychology & Neuroscience's (IoPPN) pioneering 'bench to bedside' mental health research and to meet leading scientists in the area. The Duchess continued to the Mother and Baby Unit, Royal Bethlem Hospital, South London and Maudsley NHS Foundation Trust, to meet clinicians and patients.
Year(s) Of Engagement Activity 2018
URL https://www.kcl.ac.uk/ioppn/news/records/2018/january/duchess-of-cambridge-visits-kings-college-lond...