MICA: Immuno-psychiatry: a consortium to test the opportunity for immunotherapeutics in psychiatry
Lead Research Organisation:
University of Cambridge
Department Name: Psychiatry
Abstract
Depression is a very common and potentially severe disorder. There are some treatments already available for depression, like the SSRI ("Prozac") class of anti-depressants. However, not all patients respond well to SSRI treatment: about a third of patients remain depressed. This is an area of medicine where there is a strong need to do a better job therapeutically. But there has been relatively slow progress in delivering new medicines in the last 15 years.
We propose to explore and test a radically innovative approach to finding new drug treatments for depression (and potentially other psychiatric disorders). In this project, we will focus on the idea of using anti-inflammatory drugs (like aspirin) to treat depression, especially in patients who have not responded well to SSRI treatment.
Recent scientific research has highlighted that inflammation is a major risk factor for depression. Some degree of depression is very common among patients with medical inflammatory disorders, like rheumatoid arthritis. Patients who are primarily depressed, and do not have a medical inflammatory disorder, generally have somewhat higher blood levels of inflammatory markers than non-depressed people. There is already some evidence that inflammation can block the therapeutic effects of SSRI anti-depressant drugs. And there have been some reports that anti-inflammatory drugs can have anti-depressant effects, at least in some patients with depression.
On this basis, we will address 4 key questions that need to be answered more clearly and completely before we can consider potentially more serious investment in clinical development of new anti-inflammatory drugs for depressive symptoms linked to abnormal states of the immune system.
1) Is inflammation linked to SSRI treatment resistance? 2) Do anti-inflammatory drugs have anti-depressant effects? These questions will be addressed mainly by analysis of several, large, prior datasets. For example, we will use anonymised NHS data as well as clinical trial data released by the industrial partners (GlaxoSmithKline and Johnson & Johnson) to look for new evidence linking inflammation to depressive symptoms that respond poorly to SSRI treatment. To test a particular mechanistic reason why inflammation might cause SSRI treatment failure, we will also do a number of small lab experiments, using blood samples from healthy volunteers (University of Edinburgh and GSK).
3) Can we validate immune biomarkers for depression and treatment resistance? 4) Can we use biomarkers of depression to predict which anti-inflammatory drugs are most likely to be anti-depressant? Essentially what we mean by these questions is can we develop a blood test that we can use to predict which patients with depressive symptoms are most likely to benefit from which anti-inflammatory drug? To address these questions we will again priortise analysis or re-analysis of existing data including several large biomarker collections (released by GSK) and major studies conducted by the academic partners (University College London, King's College London). We will also conduct some additional lab experiments on human blood samples.
We aim to complete this project within 2 years and then review the case for further investment in direct clinical trials of new anti-inflammatory drugs for treatment of depression in patients who have a blood test result indicating that they are inflamed and unlikely to respond well to existing anti-depressant drugs.
We propose to explore and test a radically innovative approach to finding new drug treatments for depression (and potentially other psychiatric disorders). In this project, we will focus on the idea of using anti-inflammatory drugs (like aspirin) to treat depression, especially in patients who have not responded well to SSRI treatment.
Recent scientific research has highlighted that inflammation is a major risk factor for depression. Some degree of depression is very common among patients with medical inflammatory disorders, like rheumatoid arthritis. Patients who are primarily depressed, and do not have a medical inflammatory disorder, generally have somewhat higher blood levels of inflammatory markers than non-depressed people. There is already some evidence that inflammation can block the therapeutic effects of SSRI anti-depressant drugs. And there have been some reports that anti-inflammatory drugs can have anti-depressant effects, at least in some patients with depression.
On this basis, we will address 4 key questions that need to be answered more clearly and completely before we can consider potentially more serious investment in clinical development of new anti-inflammatory drugs for depressive symptoms linked to abnormal states of the immune system.
1) Is inflammation linked to SSRI treatment resistance? 2) Do anti-inflammatory drugs have anti-depressant effects? These questions will be addressed mainly by analysis of several, large, prior datasets. For example, we will use anonymised NHS data as well as clinical trial data released by the industrial partners (GlaxoSmithKline and Johnson & Johnson) to look for new evidence linking inflammation to depressive symptoms that respond poorly to SSRI treatment. To test a particular mechanistic reason why inflammation might cause SSRI treatment failure, we will also do a number of small lab experiments, using blood samples from healthy volunteers (University of Edinburgh and GSK).
3) Can we validate immune biomarkers for depression and treatment resistance? 4) Can we use biomarkers of depression to predict which anti-inflammatory drugs are most likely to be anti-depressant? Essentially what we mean by these questions is can we develop a blood test that we can use to predict which patients with depressive symptoms are most likely to benefit from which anti-inflammatory drug? To address these questions we will again priortise analysis or re-analysis of existing data including several large biomarker collections (released by GSK) and major studies conducted by the academic partners (University College London, King's College London). We will also conduct some additional lab experiments on human blood samples.
We aim to complete this project within 2 years and then review the case for further investment in direct clinical trials of new anti-inflammatory drugs for treatment of depression in patients who have a blood test result indicating that they are inflamed and unlikely to respond well to existing anti-depressant drugs.
Technical Summary
The project will build on recent evidence that activation of the innate immune system is often associated with depressive states, and that some anti-inflammatory drugs may have anti-depressant effects, at least in some patients. It is also known that inflammatory states can modify peripheral and central monoamine signalling, and this might explain preliminary clinical data indicating that peripheral inflammation predicts resistance to monoaminergic anti-depressants.
To explore and test the therapeutic implications of these observations, we will analyse or re-analyse large prior clinical, epidemiological or experimental datatsets. NHS data will be accessed by an ethically approved system for anonymizing electronic health records in two NHS mental health trusts linked to academic partners (KCL and Cambridge). Longitudinal datasets on general population samples, including biomarker measurements, will be available through partnership with the Whitehall II and ELSA epidemiological studies (UCL). Data on randomized placebo-controlled clinical trials of anti-inflammatory drugs for medical disorders will be re-analysed with a focus on mental health questionnaire scores completed as safety endpoints (GSK and J&J). Genetic and biomarker (PBMC microarray, proteomic) case-control collections on patients with depression and other psychiatric and medical disorders will also be released by GSK. Pharmacogenetic effects will be tested by analysis of genetic and microarray data in partnership with the GENDEP study (KCL).
We will also conduct a small number of new lab experiments to measure gene expression changes in human macrophages and other PBMCs in response to pro-inflammatory and pharmacological challenges ex vivo (Edinburgh, GSK).
There will be a strong underpinning technical focus on bioinformatics and advanced statistical methods for systems or network-level analysis and visualization of complex immunophenotypes and their relationships to genetic variation (BSU).
To explore and test the therapeutic implications of these observations, we will analyse or re-analyse large prior clinical, epidemiological or experimental datatsets. NHS data will be accessed by an ethically approved system for anonymizing electronic health records in two NHS mental health trusts linked to academic partners (KCL and Cambridge). Longitudinal datasets on general population samples, including biomarker measurements, will be available through partnership with the Whitehall II and ELSA epidemiological studies (UCL). Data on randomized placebo-controlled clinical trials of anti-inflammatory drugs for medical disorders will be re-analysed with a focus on mental health questionnaire scores completed as safety endpoints (GSK and J&J). Genetic and biomarker (PBMC microarray, proteomic) case-control collections on patients with depression and other psychiatric and medical disorders will also be released by GSK. Pharmacogenetic effects will be tested by analysis of genetic and microarray data in partnership with the GENDEP study (KCL).
We will also conduct a small number of new lab experiments to measure gene expression changes in human macrophages and other PBMCs in response to pro-inflammatory and pharmacological challenges ex vivo (Edinburgh, GSK).
There will be a strong underpinning technical focus on bioinformatics and advanced statistical methods for systems or network-level analysis and visualization of complex immunophenotypes and their relationships to genetic variation (BSU).
Planned Impact
The consortium is designed to have impact on decision making about new drug development in psychiatry. The recent track record of commercial R&D investment in new drugs for depression or psychosis is poor and overall industry spend on neuroscience R&D is reducing as decision-makers prefer less risky investments.
In this context, immuno-psychiatry is potentially attractive for a number of reasons. Almost all pharmaceutical and biotech companies have expertise and assets in immunology, inflammation or biopharmaceuticals. So demonstrating that mental health disorders are immunologically tractable moves an otherwise marginal therapeutic area closer to the industry's scientific centre of gravity. More specifically, immuno-psychiatry also addresses one of the principal special risks of drug development in psychiatry - the lack of quantitative, mechanistic biomarkers of disorder or therapeutic effect. By refocusing on the immune system (not the nervous system) as the target tissue for treatment of mental health symptoms, there is an opportunity to develop peripheral blood biomarkers of immune states; blood tests that could be used, for example, to stratify depressed patients most likely to respond to an anti-inflammatory drug, and/or least likely to respond to a monoaminergic anti-depressant. If such peripherally accessible and mechanistically specific biomarkers could be validated (initially for depression) that would represent a major step toward derisking the path of clinical drug development in psychiatry.
The consortium includes two major pharmaceutical companies (Johnson & Johnson and GlaxoSmithKline) as partners. If the results of the research, which has been planned explicitly to test the promise of immuno-psychiatry, are considered positive this is likely to have immediate impact on the planning and conduct of clinical studies of new drugs for psychiatric indications. Most optimistically, the research could have commercial and social impact by catalysing industrial re-investment in areas of major unmet clinical need, associated with massive personal, social and economic costs.
In this context, immuno-psychiatry is potentially attractive for a number of reasons. Almost all pharmaceutical and biotech companies have expertise and assets in immunology, inflammation or biopharmaceuticals. So demonstrating that mental health disorders are immunologically tractable moves an otherwise marginal therapeutic area closer to the industry's scientific centre of gravity. More specifically, immuno-psychiatry also addresses one of the principal special risks of drug development in psychiatry - the lack of quantitative, mechanistic biomarkers of disorder or therapeutic effect. By refocusing on the immune system (not the nervous system) as the target tissue for treatment of mental health symptoms, there is an opportunity to develop peripheral blood biomarkers of immune states; blood tests that could be used, for example, to stratify depressed patients most likely to respond to an anti-inflammatory drug, and/or least likely to respond to a monoaminergic anti-depressant. If such peripherally accessible and mechanistically specific biomarkers could be validated (initially for depression) that would represent a major step toward derisking the path of clinical drug development in psychiatry.
The consortium includes two major pharmaceutical companies (Johnson & Johnson and GlaxoSmithKline) as partners. If the results of the research, which has been planned explicitly to test the promise of immuno-psychiatry, are considered positive this is likely to have immediate impact on the planning and conduct of clinical studies of new drugs for psychiatric indications. Most optimistically, the research could have commercial and social impact by catalysing industrial re-investment in areas of major unmet clinical need, associated with massive personal, social and economic costs.
Publications
Amasi-Hartoonian N
(2022)
Understanding treatment-resistant depression using "omics" techniques: A systematic review.
in Journal of affective disorders
Barnes J
(2017)
Genetic Contributions of Inflammation to Depression.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Bell JA
(2017)
Repeated exposure to systemic inflammation and risk of new depressive symptoms among older adults.
in Translational psychiatry
Biaggi A
(2016)
Identifying the women at risk of antenatal anxiety and depression: A systematic review.
in Journal of affective disorders
Boorman E
(2016)
Crosstalk between endocannabinoid and immune systems: a potential dysregulation in depression?
in Psychopharmacology
Borsini A
(2021)
The role of soluble epoxide hydrolase and its inhibitors in depression.
in Brain, behavior, & immunity - health
Borsini A
(2019)
The role of circulatory systemic environment in predicting interferon-alpha-induced depression: The neurogenic process as a potential mechanism.
in Brain, behavior, and immunity
Borsini A
(2018)
Interferon-Alpha Reduces Human Hippocampal Neurogenesis and Increases Apoptosis via Activation of Distinct STAT1-Dependent Mechanisms.
in The international journal of neuropsychopharmacology
Borsini A
(2020)
Pro- and anti-inflammatory properties of interleukin (IL6) in vitro: relevance for major depression and for human hippocampal neurogenesis.
in The international journal of neuropsychopharmacology
Borsini A
(2022)
Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms
in Molecular Psychiatry
Borsini A
(2020)
Characterizing anhedonia: A systematic review of neuroimaging across the subtypes of reward processing deficits in depression.
in Cognitive, affective & behavioral neuroscience
Bullmore Edward
(2018)
The Inflamed Mind: A radical new approach to depression
Cattaneo A
(2016)
Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-ß mRNA Levels Accurately Predict Treatment Response in Depressed Patients.
in The international journal of neuropsychopharmacology
Chang JP
(2020)
Cortisol, inflammatory biomarkers and neurotrophins in children and adolescents with attention deficit hyperactivity disorder (ADHD) in Taiwan.
in Brain, behavior, and immunity
Chang JP
(2021)
Cortisol and inflammatory biomarker levels in youths with attention deficit hyperactivity disorder (ADHD): evidence from a systematic review with meta-analysis.
in Translational psychiatry
Di Benedetto MG
(2020)
Nutritional and immunological factors in breast milk: A role in the intergenerational transmission from maternal psychopathology to child development.
in Brain, behavior, and immunity
Drevets WC
(2022)
Immune targets for therapeutic development in depression: towards precision medicine.
in Nature reviews. Drug discovery
Du Preez A
(2016)
Inflammatory insults and mental health consequences: does timing matter when it comes to depression?
in Psychological medicine
Dutcher E
(2020)
Early-life stress and inflammation: A systematic review of a key experimental approach in rodents
in Brain and Neuroscience Advances
Egeland M
(2015)
Molecular mechanisms in the regulation of adult neurogenesis during stress.
in Nature reviews. Neuroscience
Genel O
(2021)
The role of AQP4 in the pathogenesis of depression, and possible related mechanisms.
in Brain, behavior, and immunity
Giacobbe J
(2020)
The innate immune system and neurogenesis as modulating mechanisms of electroconvulsive therapy in pre-clinical studies.
in Journal of psychopharmacology (Oxford, England)
Giacobbe J
(2021)
A systematic, integrative review of the effects of the endocannabinoid system on inflammation and neurogenesis in animal models of affective disorders.
in Brain, behavior, and immunity
Hastings CN
(2017)
Does Diet Matter? The Use of Polyunsaturated Fatty Acids (PUFAs) and Other Dietary Supplements in Inflammation-Associated Depression.
in Current topics in behavioral neurosciences
Hepgul N
(2016)
Transcriptomics in Interferon-a-Treated Patients Identifies Inflammation-, Neuroplasticity- and Oxidative Stress-Related Signatures as Predictors and Correlates of Depression.
in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Hodgson K
(2016)
Transcriptomics and the mechanisms of antidepressant efficacy.
in European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
Huang F
(2022)
From dried bear bile to molecular investigation: A systematic review of the effect of bile acids on cell apoptosis, oxidative stress and inflammation in the brain, across pre-clinical models of neurological, neurodegenerative and neuropsychiatric disorders.
in Brain, behavior, and immunity
Innes S
(2019)
Microglial-driven changes in synaptic plasticity: A possible role in major depressive disorder.
in Psychoneuroendocrinology
Leday GGR
(2018)
Replicable and Coupled Changes in Innate and Adaptive Immune Gene Expression in Two Case-Control Studies of Blood Microarrays in Major Depressive Disorder.
in Biological psychiatry
Lynall ME
(2020)
Peripheral Blood Cell-Stratified Subgroups of Inflamed Depression.
in Biological psychiatry
Lynall ME
(2021)
B-cells are abnormal in psychosocial stress and regulate meningeal myeloid cell activation.
in Brain, behavior, and immunity
Mariani N
(2021)
Can (immune and other) gene expression help us to treat depression?
in Brain, behavior, & immunity - health
Marx W
(2022)
Diet and depression: future needs to unlock the potential.
in Molecular psychiatry
McLaughlin AP
(2022)
The influence of comorbid depression and overweight status on peripheral inflammation and cortisol levels.
in Psychological medicine
Mondelli V
(2015)
On the heart, the mind, and how inflammation killed the Cartesian dualism. Commentary on the 2015 Named Series: Psychological Risk Factors and Immune System Involvement in Cardiovascular Disease.
in Brain, behavior, and immunity
Nirmal AJ
(2018)
Immune Cell Gene Signatures for Profiling the Microenvironment of Solid Tumors.
in Cancer immunology research
Otte C
(2016)
Major depressive disorder.
in Nature reviews. Disease primers
Pariante CM
(2018)
Thirty years of Brain, Behavior, and Immunity and counting: How is the journal preparing for the future?
in Brain, behavior, and immunity
Pariante CM
(2018)
Too Much Is Still Not Enough, When Talking About Cortisol.
in Biological psychiatry. Cognitive neuroscience and neuroimaging
Pariante CM
(2018)
A parallel universe where psychiatry is like the rest of medicine.
in Epidemiology and psychiatric sciences
Pariante CM
(2016)
Neuroscience, mental health and the immune system: overcoming the brain-mind-body trichotomy.
in Epidemiology and psychiatric sciences
Pariante CM
(2015)
Psychoneuroimmunology or immunopsychiatry?
in The lancet. Psychiatry
Pariante CM
(2022)
Depression is both psychosocial and biological; antidepressants are both effective and in need of improvement; psychiatrists are both caring human beings and doctors who prescribe medications. Can we all agree on this? a commentary on 'Read & Moncrieff - depression: why drugs and electricity are not the answer'.
in Psychological medicine
Raison CL
(2018)
Interleukin (IL)-6: A good kid hanging out with bad friends (and why sauna is good for health).
in Brain, behavior, and immunity
| Description | Citation in MRC Mental Health Research Strategy |
| Geographic Reach | National |
| Policy Influence Type | Citation in other policy documents |
| URL | https://www.mrc.ac.uk |
| Description | Treasurer, Academy of Medical Sciences |
| Geographic Reach | National |
| Policy Influence Type | Influenced training of practitioners or researchers |
| Impact | The Academy of Medical Sciences (AMS) is the learned society that represents biomedical science in the UK with extensive portfolios of activity in policy, public engagement, and career development for clinical scientists. I have served as a member of Council of AMS since 2017 and as Treasure since 2019. |
| URL | https://acmedsci.ac.uk/about/governance/honorary-officers |
| Description | Wellcome Trust Strategy Award: Neuroimmunology of mood disorders and Alzheimer's disease |
| Amount | £5,000,000 (GBP) |
| Funding ID | 104025 |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2015 |
| End | 12/2020 |
| Description | Janssen, GSK and MRC ImmunoPsychiatry |
| Organisation | GlaxoSmithKline (GSK) |
| Country | Global |
| Sector | Private |
| PI Contribution | The academic partners (Cambridge, MRC BSU, KCL, UCL, Southampton, Edinburgh) have provided expertise in affective disorders, bioinformatics, macrophage biology, health informatics and epidemiology; as well as access to existing microarray and epidemiological datasets. The academic partners have also substantively contributed to analysis of microarray datasets from case-control studies of depression previously collected by the industry partners. It is notable that the Janssen collaboration initiated and supported by the MICA consortium has endured and strengthened since the end of the award, with Janssen being the major industrial partner in the Wellcome Trust funded NIMA consortium that is currently running two clinical studies of novel anti-inflammatory drugs as potential therapeutics for Alzheimer's disease and mood disorders. The total investment in immuno-psychiatry from Janssen, triggered by the MICA consortium, is now in excess of £5M. |
| Collaborator Contribution | Janssen has contributed expertise in clinical trial data analysis, bioinformatics and neurobiology of mood disorders. Specifically, Janssen has commissioned in-house re-analysis of 12 phase II/III clinical trials of anti-inflammatory drugs for non-psychiatric disorders (eg rheurmatoid arthritis) that have included mental health questionnaires as safety endpoints. These data have been re-analysed to test the hypothesis that anti-inflammatory drugs have anti-depressant effects in patients with comorbid depressive symptoms in the context of medical disorders. Janssen has also commissioned in-house re-analysis of microarray data collected as part of a prior case-control study of depression (N~100 per group). GlaxoSmithKline has contributed project management skills to support the overall organization of the consortium including regular scheduling of teleconferences and face-to-face meetings, legal negotiation of the consortium agreement between parties, and routine monitoring of work package delivery against timeline and budgetary milestones. GlaxoSmithKline has also contributed expertise in clinical trial data analysis and has commissioned in-house re-analysis of 8 phase phase II/III clinical trials of anti-inflammatory drugs for non-psychiatric disorders (eg rheurmatoid arthritis) that have included mental health questionnaires as safety endpoints. These data have been re-analysed to test the hypothesis that anti-inflammatory drugs have anti-depressant effects in patients with comorbid depressive symptoms in the context of medical disorders. The analysis of these data has been closely coordinated with the parallel effort by Janssen with the intention of producing a single joint publication. GlaxoSmithKline has also contributed expertise in bioinformatics and has enabled access to a microarray dataset collected as part of a prior case-control study of depression (N~100 per group). Analysis of these data has been led by Cambridge and MRC Biostatistics Unit and closely coordinated with the parallel effort by Janssen with the intention of producing a single joint publication. |
| Impact | In total 39 papers have been generated by the MICA consortium. Of note, in 2020, with major input from Janssen colleagues, we published a meta-analysis of published case-control studies of gene expression in major depressive disorder. The MICA consortium laid the foundations for academic-industrial partnership through the Wellcome Trust-funded NIMA consortium which is currently active with two ongoing clinical studies of novel Janssen molecules with anti-inflammatory mechanisms of action. The MICA team continues to consult with Janssen concerning identification of peripheral blood biomarkers of inflammation for use in Janssen's ongoing in-house programme of neuro-immunology and drug development. |
| Start Year | 2014 |
| Description | Janssen, GSK and MRC ImmunoPsychiatry |
| Organisation | Janssen Research & Development |
| Country | Global |
| Sector | Private |
| PI Contribution | The academic partners (Cambridge, MRC BSU, KCL, UCL, Southampton, Edinburgh) have provided expertise in affective disorders, bioinformatics, macrophage biology, health informatics and epidemiology; as well as access to existing microarray and epidemiological datasets. The academic partners have also substantively contributed to analysis of microarray datasets from case-control studies of depression previously collected by the industry partners. It is notable that the Janssen collaboration initiated and supported by the MICA consortium has endured and strengthened since the end of the award, with Janssen being the major industrial partner in the Wellcome Trust funded NIMA consortium that is currently running two clinical studies of novel anti-inflammatory drugs as potential therapeutics for Alzheimer's disease and mood disorders. The total investment in immuno-psychiatry from Janssen, triggered by the MICA consortium, is now in excess of £5M. |
| Collaborator Contribution | Janssen has contributed expertise in clinical trial data analysis, bioinformatics and neurobiology of mood disorders. Specifically, Janssen has commissioned in-house re-analysis of 12 phase II/III clinical trials of anti-inflammatory drugs for non-psychiatric disorders (eg rheurmatoid arthritis) that have included mental health questionnaires as safety endpoints. These data have been re-analysed to test the hypothesis that anti-inflammatory drugs have anti-depressant effects in patients with comorbid depressive symptoms in the context of medical disorders. Janssen has also commissioned in-house re-analysis of microarray data collected as part of a prior case-control study of depression (N~100 per group). GlaxoSmithKline has contributed project management skills to support the overall organization of the consortium including regular scheduling of teleconferences and face-to-face meetings, legal negotiation of the consortium agreement between parties, and routine monitoring of work package delivery against timeline and budgetary milestones. GlaxoSmithKline has also contributed expertise in clinical trial data analysis and has commissioned in-house re-analysis of 8 phase phase II/III clinical trials of anti-inflammatory drugs for non-psychiatric disorders (eg rheurmatoid arthritis) that have included mental health questionnaires as safety endpoints. These data have been re-analysed to test the hypothesis that anti-inflammatory drugs have anti-depressant effects in patients with comorbid depressive symptoms in the context of medical disorders. The analysis of these data has been closely coordinated with the parallel effort by Janssen with the intention of producing a single joint publication. GlaxoSmithKline has also contributed expertise in bioinformatics and has enabled access to a microarray dataset collected as part of a prior case-control study of depression (N~100 per group). Analysis of these data has been led by Cambridge and MRC Biostatistics Unit and closely coordinated with the parallel effort by Janssen with the intention of producing a single joint publication. |
| Impact | In total 39 papers have been generated by the MICA consortium. Of note, in 2020, with major input from Janssen colleagues, we published a meta-analysis of published case-control studies of gene expression in major depressive disorder. The MICA consortium laid the foundations for academic-industrial partnership through the Wellcome Trust-funded NIMA consortium which is currently active with two ongoing clinical studies of novel Janssen molecules with anti-inflammatory mechanisms of action. The MICA team continues to consult with Janssen concerning identification of peripheral blood biomarkers of inflammation for use in Janssen's ongoing in-house programme of neuro-immunology and drug development. |
| Start Year | 2014 |
| Title | Sirukumab Phase 2 trial for Major Depressive Disorder |
| Description | Sirukumab is an anti-IL6 antibody in development for inflammatory disorders by GSK and Janssen. In 2015, Janssen initiated a phase 2 trial of sirukumab for patients with MDD suboptimally responsive to conventional anti-depressants and with baseline C-reactive protein greater than 3mg/L. MRC ImmunoPsychiatry consortium members contributed to the protocol for this study, including provision of supporting data from re-analysis of mental health endpoints from clinical trials on sirukumab and other anti-inflammatory drugs in non-psychiatric indications. The study is currently recruiting and is expected to read out in 2017. To the best of our knowledge, this is the first immunologically stratified phase 2 study of an anti-inflammatory drug for depression (or any other psychiatric disorder). |
| Type | Therapeutic Intervention - Drug |
| Current Stage Of Development | Early clinical assessment |
| Year Development Stage Completed | 2016 |
| Development Status | Under active development/distribution |
| Clinical Trial? | Yes |
| Impact | The study is currently recruiting and will read out in 2017 |
| URL | https://clinicaltrials.gov/ct2/show/NCT02473289?term=sirukumab+depression&rank=1 |
| Description | Annual Psychoneuroimmunology Research Society (PNIRS) Conference |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | PNIRS is the leading research society internationally dedicated to understanding bidirectional interactions between immune and nervous systems, and past and current members of PNIRS have been responsible for generating much of the empirical data and conceptual framework now being built on by immunopsychiatry. The conference is organised by Dr Neil Harrison (MRC Consortium collaborator) and will feature presentations of the consortium's work. |
| Year(s) Of Engagement Activity | 2016 |
| URL | http://pnirs.org/meetings/index.cfm |
| Description | Festivale dell Mente |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Ed Bullmore was invited to give a presentation at Festivale delle Mente, Italy's leading book festival, on "The Inflamed Mind", 25 August 2019 |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.festivaldellamente.it/it/festival-della-mente-16-edizione-dal-30-agosto-al-1-settembre-2... |
| Description | Hexham Book Festival, invited talk |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | This was a talk about the ideas in my book "The Inflamed Mind" |
| Year(s) Of Engagement Activity | 2019 |
| Description | Interview fo regional TV news |
| Form Of Engagement Activity | A broadcast e.g. TV/radio/film/podcast (other than news/press) |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | BBC Look East, regional news programme, interviewed me about a new study starting in Cambridge to test anti-inflammatory drugs for efficacy in patients with depression. |
| Year(s) Of Engagement Activity | 2018 |
| URL | https://www.neuroimmunology.org.uk |
| Description | Nature Medicine feature on anti-inflammatory drugs as anti-depressants |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I was interviewed and quoted in a feature article on immuno-psychiatry in Nature Medicine |
| Year(s) Of Engagement Activity | 2017 |
| URL | http://www.nature.com/articles/nm0917-1009 |
| Description | RCPsych ImmunoPsych Symposia |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Professional Practitioners |
| Results and Impact | Royal College of Psychiatrists Annual Meeting - symposia presentations to practitioners on status of inflammation as a cause / predictor of treatment resistant depression (Prof C Pariante) |
| Year(s) Of Engagement Activity | 2015 |
| Description | The Inflamed Mind |
| 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 | Public/other audiences |
| Results and Impact | In 2018, I published a book - "The Inflamed Mind" (Short Books, London) - which was written to communicate some of the background science about neuro-immunology and immuno-psychiatry to a general readership. The book has been highly successful and was listed as a best-seller by the Sunday Times. I participated in many media opportunities to promote the book and to discuss the issues it raised, including: BBC Radio 4, Today programme BBC Radio 2, Jeremy Vine Show BBC Radio 4, Start the Week |
| Year(s) Of Engagement Activity | 2018 |
| URL | http://www.theinflamedmind.co.uk |