Bipolar Lithium Imaging Structure and Spectroscopy

Lead Research Organisation: Newcastle University
Department Name: Institute of Neuroscience

Abstract

Bipolar disorder is a common psychiatric illness characterized by periods of depression (low mood, loss of enjoyment, reduced energy) and mania (elevated mood, racing thoughts, disturbed behaviour). Relapses can occur frequently and many patients do not fully recover between episodes, struggling with mood fluctuations and poor concentration. Bipolar disorder is highly disabling, seriously disrupting health, family relationships, social circumstances and occupational status. Lifespan is reduced on average by 9 years and one third of patients attempt suicide. Stability in life is undermined by the threat of relapse, the risk of which increases with each episode of illness.

Numerous medications are effective in acute episodes but in patients with a recurrent illness, maintenance treatment is advisable. A goal of maintenance treatment is the prevention of relapse and drugs which are capable of this are called mood stabilisers. Lithium is a unique mood stabiliser, treating and preventing mania and depression whilst reducing suicidal behaviour. To be effective against relapse, patients must take lithium for a long time at an adequate dose. The dose is determined by the lithium level in the blood, aiming for a level which is known to be effective but lower than that at which toxicity occurs.

Whilst a substantial proportion of patients have a good response to lithium, the rest experience a partial or limited response, or are unable to tolerate the side effects, despite having blood levels within the therapeutic range. Potential responders may be identified clinically, having a higher age of onset and a pattern of illness in which mania is followed by depression. Those in whom depression precedes mania do poorly with lithium, as do patients with constant cycling or numerous hospital admissions. However, the ability of these observations to predict response to lithium is fairly poor. Further, they are of limited value for patients early in the course of their illness in whom a pattern of illness has not yet emerged. Reliance on such predictors could mean that lithium initiation is delayed well past the point at which it was first indicated.

Understanding the mechanism of action of lithium might lead to a better way of determining which patients would be most likely to benefit from taking it. Whilst much is known about what effects lithium has, we lack a satisfactory account of its mode of action in bipolar disorder. It regulates the transmission of signals in the mood circuits of the brain, altering the concentration of key chemicals and the tendency for nerve cells to respond to a stimuli. It has been shown that lithium protects the brain from the damaging effects of psychiatric illness, stimulating the regeneration of damaged nerve cells and possibly even the growth of new brain tissue. Recent advances in brain imaging techniques mean that many of these effects can be safely and non-invasively detected using a magnetic resonance scanner.

My research will explore the relationship between the clinical effects of lithium and magnetic resonance estimates of its actions on the brain. Using advanced scanning techniques I will examine brain structure and composition in a group of patients with bipolar disorder taking lithium and compare the results against a group of patients with bipolar disorder taking other long term medications (and naive to lithium). Having thus identified potential markers of the effects of lithium, I will explore the extent to which each magnetic resonance measure accounts for the degree of response to lithium or the severity of its side effects. I will also determine the distribution of lithium in the brain using a novel adaptation of our magnetic resonance scanner - currently only available in our University. I expect that direct measures of brain lithium concentration will inform our understanding of its actions and improve the prediction of response compared to routine blood monitoring.

Technical Summary

AIM: To better understand lithium response in bipolar disorder (BD).

OBJECTIVES:
1. Comprehensively evaluate the effects of lithium on the brain in BD.
2. Optimise and advance lithium multinuclear magnetic resonance (MR) techniques.
3. Characterise lithium response using clinical and biological data.

METHODS:
Euthymic adults with BD (type I or II) recruited from NE of England healthcare services, excluding patients with contraindications to MR scanning, current/recent harmful drug or alcohol use, comorbid diagnosis, impairment of capacity or current detention. Cross-sectional study of two groups: i) BD patients taking lithium for up to 5 years (n=80); ii) matched BD patients taking other mood stabilisers but naive to lithium (n=40). In a structured interview, diagnosis will be confirmed and a thorough clinical and archival assessment of each patient's BD undertaken. Blood samples will be taken for medication levels. Patients will complete tests of psychomotor processing speed and attention. MR sequences will include anatomical, quantitative relaxometry, diffusion tensor imaging, proton and phosphorous spectroscopy plus quantitative lithium spectroscopy and novel whole brain lithium imaging.

ANALYSIS
Complementary MR analyses to explore the influence of lithium within the frameworks of its actions on neuroprotection, cellular hydration and biophysical changes to the MR signal. With respect to lithium response, a new rating system will be developed; comparative and correlative analysis of MR, cognitive and clinical data will be performed; patients will also be clustered purely on the basis of their MR data before back-referencing to clinical characteristics.

NOVEL OUTPUT
1. A new clinical tool for rating lithium response, suitable for future prospective investigation of predictive factors.
2. High resolution 3D Li7 imaging.
3. Robust MR measures of lithium's effects (accounting for its actions on hydration and signal generation)

Planned Impact

As with all high quality clinical translational research, my work will impact positively on patients, clinicians and health service providers, and advance the global scientific knowledge base whilst simultaneously equipping the future generation of academics with the skills and tools necessary to investigate and address a breadth of health disorders.

The academic beneficiaries of this research have been outlined, but it is important to reiterate that the innovative methodologies and techniques that will arise from this project hold great potential to advance our capability to investigate the basis and treatment of many psychiatric and neurological conditions. The health of psychiatric and imaging disciplines will be enhanced and highly skilled researchers delivered into the field.

Research validating the biological basis of mental illness and its treatment reduces the stigma associated with these conditions. Evidenced by the keen support offered from BipolarUK, research leading to the ability to establish effective treatment at an early stage in bipolar disorder is highly desirable. A greater understanding of the effects of lithium on the brain, in particular its concentration and distribution with respect to response, will directly influence practice. The capacity to titrate lithium dose according to brain concentration may lead to better outcomes and fewer side effects compared to traditional serum monitoring. Unlike other mood stabilisers, lithium reduces suicidal behaviour - research raising the profile and guiding the effective use of lithium will improve health outcomes globally.

This research will have an economic impact directly on the NHS and in a wider sense for the UK. Bipolar disorder is a highly disabling condition associated with substantial direct and indirect socioeconomic costs, many of which are related to the duration of time spent unwell and the delay between presentation, diagnosis and the initiation of effective treatment regimes. Early intervention by specialist services improves outcomes and the ability to predict treatment response with confidence at, or near first presentation would substantially reduce the burden of bipolar disorder across all measures. Compared to lithium, prescription costs for atypical antipsychotics (commonly used in maintenance treatment) are an order of magnitude greater.

The UK is the only country in Europe, and one of a handful worldwide, actively researching multinuclear lithium magnetic resonance spectroscopy. Not only will this research ensure that we remain competitive, but in advancing from spectroscopic detection to true lithium imaging, the UK will be established as the leader in the field. The competitive advantage of my research has been embraced by colleagues in industry. In advertising the advanced capabilities of their magnetic resonance scanner systems at scientific and industry meetings, Philips (Best, The Netherlands) actively promote my methods and results. This mutually advantageous relationship will be developed and formalised during my proposed research.
 
Description FMS Engagement
Amount £2,000 (GBP)
Organisation Newcastle University 
Sector Academic/University
Country United Kingdom
Start 11/2014 
End 11/2015
 
Description H2020 SC1-PM-02-2017
Amount € 7,707,532 (EUR)
Funding ID 754907 
Organisation European Commission H2020 
Sector Public
Country Belgium
Start 01/2018 
End 12/2022
 
Description Newcastle University Summer Student Stipend
Amount £3,000 (GBP)
Organisation Newcastle University 
Sector Academic/University
Country United Kingdom
Start 06/2015 
End 09/2015
 
Description Royal College of Psychiatrists Small Project Funding
Amount £684 (GBP)
Organisation Royal College of Psychiatrists 
Sector Learned Society
Country United Kingdom
Start 04/2016 
End 11/2017
 
Title High resolution lithium imaging 
Description Advanced imaging technique for the assessment of brain lithium distribution using a commissioned birdcage head coil. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Initial results indicate that lithium is not evenly distributed in the brain, something previously not clear in humans. 
 
Title Lithium phantom 
Description Developed and constructed brain representative test objects for lithium imaging, permitting the harmonisation of lithium imaging across multiple research centres. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? No  
Impact Harmonisation of research centre imaging sequence development for lithium MRI. Notable impacts will develop through collaboration. 
 
Title SSFP Lithium MRI 
Description An improvement to the high resolution lithium imaging. Swifter acquisition and better resolution through the use of steady state free precession sequences. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact This technique has charted the distribution of lithium in the brain. Notably we have seen inhomogeneous distribution and strong signal from the eyes. This has opened a new preclinical line of investigation into the optic effects of lithium. 
 
Title BLISS-DB 
Description We are developing a database for the collection of data specific to clinical and neuropsychological assessment of bipolar disorder. This has been developed in house but will likely be formalised by internal University computing services or external consultants. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact This is the first relational database to be applied in our department and will likely be used widely by other groups once established. 
 
Title NetSCID 
Description We have joined NetSCID as approved alpha and beta testers. This tool allows us to undertake structured diagnostic interviews for psychiatric disorders using a secure web-based tool rather than cumbersome paper versions. It has dramatically improved the interview process and reduced data entry time. Local groups have since adopted this process. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact Shortened interview times. Removed need for manual data entry. 
URL https://netscid.telesage.com/alpha/Account/LogOn?ReturnUrl=%2falpha%2fHome%2fAdmin
 
Description NeuroSpin 
Organisation Neurospin
Country France 
Sector Private 
PI Contribution Advice on the development of lithium spectroscopy and imaging using MR techniques.
Collaborator Contribution Development of rating and monitoring of response to lithium in the long term treatment of bipolar disorder.
Impact Collaboration has resulting in our partners being awarded a high profile ANR grant.
Start Year 2014
 
Description R-LiNK 
Organisation ACOBIOM
Country France 
Sector Private 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Aix-Marseille University
Country France 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Alternative Energies and Atomic Energy Commission (CEA)
Country France 
Sector Public 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Brescia Fatebenefratelli
Country Italy 
Sector Hospitals 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation European Clinical Research Infrastructure Network
Country France 
Sector Charity/Non Profit 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Ludwig Maximilian University of Munich (LMU Munich)
Country Germany 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation National Center for Scientific Research (Centre National de la Recherche Scientifique CNRS)
Country France 
Sector Public 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation National Institute of Scientific Research (INRS)
Country Canada 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Poznan University of Medical Sciences
Country Poland 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Public Assistance - Hospitals of Paris
Country France 
Sector Hospitals 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation Technical University of Dresden
Country Germany 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation University of Barcelona
Department Psychiatry Barcelona
Country Spain 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation University of Copenhagen
Country Denmark 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation University of Gothenburg
Country Sweden 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description R-LiNK 
Organisation University of Milan
Country Italy 
Sector Academic/University 
PI Contribution Contributions to the design and development of an allocation for H2020 funding (SC1-PM-02-2017). Specifically the use and application of true lithium imaging in the brain of man. I coordinated the efforts of 5 centres developing this technique as part of a funding bid which was successful.
Collaborator Contribution The efforts of the partners related to the wider aspects of the proposal. The objectives of this proposal are: (i) to improve the outcome of individuals with bipolar I disorder (BDI) by optimizing the stabilization of their mental state through the application of stratified approaches; (ii) to improve the early prediction of response to the most widely recommended first line mood stabilizer (lithium/Li) using a set of multi-modal biomarkers; (iii) to develop a multidisciplinary international network of experts - Response to Li NetworK (R-LiNK) to undertake this project and to examine personalized diagnostics and personalized therapeutics of BD and (iv) to implement new and powerful technologies such as Magnetic Resonance Imaging (Li7-MRI) to characterise brain Li distribution or "omics" approaches (a term we use to refer to genetic, transcriptomic (total blood RNA, circulating miRNA), metabolomic, proteomic and kinomic studies) to characterize the molecular signature of Li in responders and non-responders.
Impact H2020 funding (SC1-PM-02-2017) awarded (€7.8M)
Start Year 2016
 
Description EPA conference Nice 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Symposium on the prediction of lithium response. Presented new findings from the development of 7Li-MRI
Year(s) Of Engagement Activity 2018
URL http://www.epa-congress.org/2018/Pages/default.aspx#.Wp6R0maZPeQ
 
Description ICNPT Crete 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation on lithium imaging to 4th International Congress on Neurobiology, Psychopharmacology and Treatment Guidance, Crete
Year(s) Of Engagement Activity 2015
 
Description ISBD SymposiumAmsterdam 2016 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lecture on the development of brain lithium imaging
Year(s) Of Engagement Activity 2016
 
Description International conference presentation Biological Psychiatry New York 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Symposium presentation outlining the development of lithium imaging and the colocalisation of brain lithium and its effects on white matter
Year(s) Of Engagement Activity 2018
 
Description Lecture to RCPsych General Adult Faculty meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation of General Adult Psychiatrist attending a national conference. Discussed the impact of diagnostic constructs with respect to response, together with a psychologist college.
Year(s) Of Engagement Activity 2017
 
Description NCMD inaugural lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Public lecture on bipolar disorder and lithium.
Year(s) Of Engagement Activity 2015
 
Description NCMD lecture 2017 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Northern Centre for Mood Disorders Conference
Year(s) Of Engagement Activity 2017
 
Description NCMD meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Lecture updating on the BLISS study to those consultants involved in referring patients
Year(s) Of Engagement Activity 2018
 
Description NCMD research network launch 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Laugh of coordinated research network for bipolar disorder
Year(s) Of Engagement Activity 2015
 
Description PCRN meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Study presentation to primary care research network
Year(s) Of Engagement Activity 2016
 
Description Poster and presentation to British Chapter ISMRM 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Poster and invited oral presentation at conference. First presentation of methods of lithium imaging.
Year(s) Of Engagement Activity 2016
 
Description Presentation to Manchester Psychiatrists 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Update to consultant colleagues on the treatment of bipolar disorder and the potential impact of lithium imaging on predicting response
Year(s) Of Engagement Activity 2017
 
Description RCPsych Adult Faculty conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation on dopaminergic antidepressants
Year(s) Of Engagement Activity 2015
 
Description RCPsych Adult Faculty conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation on the use of lithium in practice
Year(s) Of Engagement Activity 2015
 
Description RCPsych International Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Lecture on mechanisms of treatments in bipolar disorder
Year(s) Of Engagement Activity 2015
 
Description TEWV Update on Bipolar Disorder 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Update to consultant colleagues on the treatment of bipolar disorder and the potential impact of lithium imaging on predicting response
Year(s) Of Engagement Activity 2017