The research of the Dept. of Immunology, ErasmusMC, deals in particular with the translation of basic immunology to the clinic. Apart from investigating basic immunological processes (e.g. the differentiation of monocytes, macrophages, dendritic cells, T cells and B cells from their precursors; cytokine and transcription factor networks) the department therefore focuses on the study of various autoimmune diseases (e.g. Hashimoto’s thyroiditis, type 1 diabetes, multiple sclerosis, psoriasis, the Guillain-Barré syndrome and Sjögren’s disease), of leukemia’s and lymphoma’s (e.g. immune tests for an early diagnosis) and primary immune deficiencies.
To fulfill its mission the Dept. of Immunology, Erasmus MC, is subdivided, regarding its organization, into 4 scientific units (Autoimmunity, Immune regulation, Leukemia/Lymphoma, Immune deficiencies), an outpatient department and a laboratory for routine immunological test.
The focus of the unit Autoimmunity is on the pathogenesis of endocrine autoimmune disease (e.g. Hashimoto’s thyroiditis, type 1 diabetes), the pathogenesis of major psychiatric diseases (e.g. bipolar disorder, major depression, schizophrenia and post partum psychosis), the relationship between endocrine autoimmune and major psychiatric diseases (so-called neuro-immuno-endocrine interactions) and the key role of abnormal pro-inflammatory monocytes, macrophages and dendritic cells in causing these diseases.
In this research the Dept of Immunology works closely together with the Dept of Psychiatry, which is in particular interested in depression and psychosis in the post partum period and disturbed mother-child relationships as consequence of these disorders.
Ludwig Maximillian University
The Psychoneuroimmunology research group of the Psychiatric Hospital of the Ludwig-Maximilian University, Munich, Germany, is exploring the role of the immune system during psychological processes and in psychiatric disorders since 1985. Schizophrenia, depressive disorders, anxiety disorders, Alzheimer’s disease, tic disorders and Tourette syndrome are of main interest. The influence of infectious processes and latent chronic inflammatory processes in certain regions of the CNS are in the focus of our research.
Our projects in the MOODINFLAME consortium will contribute to (1) the translation of basic immunology, neurobiology and pathophysiology to the clinic, (2) biomarker research in psychiatric disorders from the immune and neurochemical systems interaction and (3) development of new therapeutics through experimental and clinical studies. The research work bases on the immune activation induced by physical or infectious stress which in turn induces the imbalances in tryptophan catabolism and related glutamatergic and other neurochemical changes in mood disorders. The research group is composed of a clinical research unit and a laboratory unit with a neurochemical research section and an in vitro and animal experimental research section. The clinical research section emphasizes on phase II clinical studies; in collaboration with the clinical section and the experimental section, the neurochemical section emphasizes on biomarker research; and the experimental section emphasizes on investigating further basic pathophysiogical mechanisms and preclinical studies for new therapeutics and preventive measures.
In the MOODINFLAME project, the research group will (1) carry out basic and translational in vitro (glial and neuronal cultures) and in vivo studies (gestational stress or prenatal stress in mice) on the immune system and tryptophan metabolism related pathophysiology; additionally, on new therapeutic and preventive approaches using inhibitors of enzymes of the tryptophan/kynurenine metabolism, (2) participate in the standardization of tryptophan pathway biomarker analyses and the validation of these markers in clinical and experimental samples, (3) participate in multicentre clinical data and sample collection for biomarker studies in the consortium, and (4) coordinate a phase II clinical study on anti-inflammatory cyclooxygenase-2 therapy. Our centre will collaborate also with other non-EU collaborators from the University of New South Wales, Australia and the University of Illinois, United States of America.
www.pni-net.de ; psywifo.klinikum.uni-muenchen.de
University of Muenster
Department of Psychiatry, University of Münster
The Department of Psychiatry and Psychotherapy at the Münster University Hospital (Head: Prof. Volker Arolt, M.D., Ph.D.) is a clinical and research institution that was built to take care of patients with mental illnesses. The clinical unit has a longstanding tradition in the diagnosis and therapy of affective disorders. In addition, there are units for emergency psychiatry and mentally ill with severe somatic diseases, for intensive psychotherapy, and for the focused treatment of psychotic disorders. The 5 wards of the department supply 95 beds. Our day clinic can accommodate up to 18 patients, and we maintain a large outpatient service.
In a number of research programs, the relationship between affective and anxiety disorders and their neuronal, molecular, and genetic underpinnings are explored. Our research projects also aim to detect biological markers for pathogenesis, disease progression, and perpetuation. The research programs at the Department of Psychiatry and Psychotherapy focus on the following main topics:
- Molecular psychiatry employing genetic and epigenetic methods, but also exploring phenotypic aspects regarding receptor function and animal models of behaviour
- Clinical and experimental psychoneuroimmunology
- Brain imaging
- Neuropsychological research with a focus on emotion processing
- Psychotherapy research
- Clinical research (depression, anxiety disorders, schizophrenia)
In the Moodinflame project, a specially formed clinical research group is responsible for the recruitment of patients with mood disorders and for blood sample collections, according to the regulations of the EU consortium. To this aim, the collaborative research group relies on a network of 4 different psychiatry departments in Westphalia. We use samples of patients and of healthy controls for the development of biomarker tests in order to identify and characterize patients with mood disorders and individuals at risk more easily and with higher validity. In this context, one of our main research interests is the disturbed microglia-astrocyte-neuron interaction with a special focus on S100B and BDNF as potential biomarkers for the detection of mood disorders.
Silke Jörgens, PhD
Coordinator of Clinical Research Group
University Hospital Muenster
Department of Psychiatry and Psychotherapy
Tel ++49 251 8351802
University of Groningen
The clinical research program on affective disorders (mood and anxiety disorders) currently mainly encompasses bipolar disorders and (unipolar) depressive disorders and is embedded in the Interdisciplinary Center for Psychiatric Epidemiology (ICPE). In addition to the epidemiological studies of the ICPE mainly involving large cohorts form the general population including healthy controls, the Department of Affective Disorders of the University Center for Psychiatry (UCP) aims to perform clinical studies in which the patients of the department can participate. Moreover, several clinical studies are performed in combination with mental health institutes elsewhere, and with the Departments of General Medicine, Internal Medicine, Cardiology and Geriatrics of the University Medical Center Groningen ,(UMCG).
The main research projects are the Netherlands Study of Depression and Anxiety (NESDA), a multi-site naturalistic cohort study to describe the long-term course and consequences of depressive and anxiety disorders, and to integrate biological and psychosocial research paradigms within an epidemiological approach in order to examine (interaction between) predictors of the long-term course and consequences; MOODINFLAME, a multi-site study European study investigating inflammation, among other in patients with mood disorders (in Groningen bipolar disorders); studies of cognitive functioning of patients with bipolar disorders or depressive disorders; a multi-site RCT studying the effect of CBT and/or antidepressants in the prevention of recurrences in patients with recurrent major depression; a multi-site RCT studying the effect of a cognitive training to prevent the onset of a mood or anxiety disorder among children of a parent with a depressive or anxiety disorder; and various studies on the treatment of winter depression.
Within the UMCG/RuG collaborations have been established with several partners: the Neuroimaging Center (NIC) for fMRI studies; the Department of Nuclear Medicine for PET studies; the Department of Epidemiology, and the Department of Psychology of the Faculty of Behavioral and Social Sciences , and the Department of Chronobiology of the Faculty of Mathematics and Natural Sciences.
University of Innsbruck
Research in the Department of Biological Psychiatry at the Medical University Innsbruck focuses on the following main areas:
- quality of life and patient reported outcomes
- alcohol related psychiatric disorders
“Moodinflame” represents an important project in psychoimmunology research. The Laboratory of Experimental Alzheimer Research (Christian Humpel) studies the neurodegeneration of serotonergic neurons in organotypic brain slices of the dorsal raphe. We will study whether inflammation induces cell death in these neurons and if neurodegeneration can be counteracted by growth factors or anti-inflammatory molecules. We also aim to study co-expression of indoleamine-2,3-dioxygenase (IDO) in serotonergic neurons, microglia and astrocytes. This study is performed by a PhD student (Tanja Hochstrasser). In addition we are interested in the role of human monocytes and platelets in diagnosing major depression.
In the clinical part of “moodinflame” we investigate patients with major depression and bipolar affective disorder according to the study protocol. Furthermore, we explore three additional research topics on the same patient population:
- neurocognitive dysfunction in patients with affective disorders
- suicidality in patients with affective disorders and
- osteoporosis in patients with affective disorders.
University Psychiatric Centre KU Leuven
The University Psychiatric Centre KU Leuven has a long tradition in the field of scientific research in mood disorders and psychiatric epidemiology. More specifically, the GRASP (Genetic research about stress and psychiatry) research unit focuses on the genetic background underlying the different psychiatric diseases, using the role of the Hypothalamic-Pituitary-Adrenal gland – Axis (HPA-axis) in different psychiatric diseases as an endophenotype. The principal investigator leading GRASP is Stephan Claes, MD, PhD.
Currently, GRASP is involved in the several research project, such as endophenotypes of depression with focus on HPA-axis, prenatal stress and the link with the stress-reactivity of the newborn, chronic fatigue syndrome genetics, schizophrenia genetics focusing on the gamma-secretase pathway, and the Moodinflame project.
Our involvement in the Moodinflame project consists out of several aspects. First, we include patients with major depression and bipolar affective disorder according to the study protocol. Second, we will study HPA-axis abnormalities in patients with major depression and bipolar affective disorder by measuring cortisol-levels in saliva through a dexamethasone-suppresion test. Finally, we will study interrelations between the presence of the pro-inflammatory signature/ biochemical signs of an abnormal tryptophan catabolism, HPA-axis abnormalities and relevant gene polymorphisms. Therefore, we plan a SNP (single nucleotide polymorphism) based haplotype study on candidate genes related to the function of the Hypothalamic Pituitary Adrenal (HPA) axis and in candidate genes involved in immune function.
Section of Perinatal Psychiatry and the Stress, Psychiatry and Immunology laboratory (SPI-Lab)
The Section of Perinatal Psychiatry and the Stress, Psychiatry and Immunology laboratory (SPI-Lab), seek to understand the body’s response to stress and the mechanisms in relation to how it contributes to the manifestation of psychological symptoms. We have a strong emphasis on biological and molecular research relevant to mental health, using biological samples derived from patients’ populations and laboratory models. We focus particularly on the role of stress hormones and inflammatory responses in regulating behaviour, in the pathogenesis of depressive and psychotic symptoms, and in the therapeutic action of psychotropic drugs. Ultimately, our goal is to identify biomarkers that are clinically relevant and that have the potential to lead to the development of new and more effective treatments. The Section is led by Dr Carmine Pariante, Reader in Biological Psychiatry and Lead Consultant for the Liaison Perinatal Psychiatry Services at King’s College Hospital.
Scientifico Universitario Ospedale San Raffaele
Clinical research group Psychiatry and Clinical Neurosciences at the Division of Neurosciences of the Istituto Scientifico Universitario Ospedale San Raffaele
Our group works at the interface between neuroscience and behavioral disorders. We use genetics, in vivo imaging, clinical psychobiology, pharmacology, neuropsychology, neurophysiology, and clinical research instruments to increase knowledge and develop effective diagnosis and treatment options. People and structures encompass the clinical units of psychiatry, sleep medicine, and clinical psychology. The unit includes a fully equipped psychiatric genetics laboratory and is founding member of the C.E.R.M.A.C. (Center of excellence for high-field magnetic resonance imaging). Our scientific activity began in 1988, and has increased over time. In the field of psychiatry we ranked at the 1st place among psychiatric research structures in Italy, and at the third place in Europe in the field of mood disorders (2006, cumulative I.F. 417.0).
Foundation Biological Psychiatry
Foundation Biological Psychiatry (FBP) is an independent non-profit organization, working for public benefit, dedicated to research, education and other activities in preventing, improving and restoration of psychic health. It is specialized in stimulating and realizing scientific research, educational activities, spreading of new professional information and knowledge and international communications and cooperation with other organizations in the field of psychiatry and psychology.
FBP has involved in several national and international educational projects, as Prime coordinator or Technical Coordinator of the activities of the existing departments of psychiatry and psychology at the Universities and Medical Universities in the country and abroad (Spain – Madrid, UK – Manchester, France, Germany – Munich, Sweden, Austria – Vienna, Greece – Athens, Turkey – Bursa, Australia – Melbourne, Perth, etc.). The projects involved the issuing of education CDs.
At present the Foundation participates in an EU granted project on immunogenetics of patients with depression and bipolar disoder.
FBP is accredited by the Bulgarian Union of Physicians and the WFSBP to assure educational and consultancy missions.
FBP has focused its activities in the domain of modern educational and scientific services: mainly in the fields of biological psychiatry and biological psychology, measurement and testing of psychopathological rating scales, distributions of knowledge on modern diagnostic and treatment software/information technologies with medical applications dedicated to psychic health.
The educational and scientific services offered may be summarized as being:
- Development of new diagnostic and treatment abilities
- Expert evaluation and assessment
- Research tasks, including bibliography survey, epidemiological studies and technology watch services
- Psycho-education and information for the patients, doctors and the general population, supported by recent technical innovations
Some preplanned activities for 2009-2010:
- Continuing the work on MOODINFLAME project
- Organization of an epidemiological study on bipolar disorders
- Validation of international questionnaires on bipolar disorder
- Education of patients in social functioning abilities, development and distribution of patients’ diaries, informational services. Prevention of obesity
- Educational activities with psychiatrists and psychologists on different themes
- Organization of an epidemiological study on sleep disorders in the general population of Bulgaria
Dr Olya Mikova, President of FBP
8, Svilenitsa str
Tel/Fax: +359 2 8511740
Mobile: +359 888 897555
Trinity College Institute of Neuroscience (TCIN) in Dublin is participating in the collaborative, large-scale research project entitled “Early diagnosis, treatment and prevention of mood disorders targeting the activated inflammatory response system. [Acronym: MOODINFLAME] funded under FP7. In TCD the MOODINFLAME research team comprises, two lead academic researchers (Dr. Thomas Connor & Dr. Andrew Harkin), a post-doctoral researcher (Dr. Sinead Gibney) and two PhD students (Aine Daly and Eimear Fagan). Dr. Gibney is a graduate in zoology and holds a PhD with postdoctoral experience in anatomy/neuroscience. She brings extensive experience in glial cell biology, and in animal models of depression and visceral hypersensitivity to the MOODINFLAME project. Aine Daly holds a BSc in Pharmacology and an MSc in Neuroscience, and Eimear Fagan holds a BA (Mod.) in Neuroscience.
Our laboratory is an INSERM laboratory hosted at the Ecole Normale Supérieure. INSERM is the most important french governmental agency aimed at medical research. The Ecole Normale Supérieure, which is located in the historical center of Paris, is one of the leading french institution for research and teaching, providing an exceptionally wide framework of scientific excellency. The Institute
of Biology of the Ecole Normale Supérieure, comprises 30 independent teams mainly focussed on neurobiology and development.
We want to decipher the relationship between microglia and synaptic function in physiopathological contexts using animal models. We arecombining the most up-to-date approaches in imaging, histochemistry, electrophysiology together with a large repertoire of cell biology technologies. We already demonstrated that in mouse, prenatal inflammation is sufficient to impact synaptic function. Within the
consortium, we establish the impact of inflammation on synaptic function in adult and we describe the molecular and cellular mechanisms of these pathological interactions.
We have most exciting scientific discussions with our psychiatrist and immunologist colleagues that allows us to position our molecular and
cellular work in the context of mood disorders. In addition, the interactions within the “in vitro group” of the consortium has raised discussion and solutions about scientific and technical issues related to microglia and inflammation.
University of Uppsala
The department Genetics and Pathology at Uppsala University conducts advanced research and education in areas such as medical and clinical genetics, immunology, pathology, tumor biology and vascular biology. The research within the MoodInflame consortium is focused on the regulation of inflammatory genes in monocytes and their impact on monocyte function. The regulatory functions of inflammatory genes, defined through gene expression studies, are investigated using siRNA/shRNA knock-down and vector based expression strategies. The epigenetic mechanisms controlling transcription of the genes involved are studied in detail. The overall goal of the research within the MoodInflame project is to gain a clearer understanding of the regulatory network in monocytes that direct inflammatory gene expression in psychiatric disease.
Advanced Practical Diagnostics N.V. (apDia)
The mission of Advanced Practical Diagnostics n.v. Belgium is to develop technically advanced, user-friendly and cost-effective diagnostic materials in the area of safe blood banking, infectious diseases, inflammatory related markers for special profiles such as cardiac diseases, rheumatology and autoimmune diseases and psychiatric and neurodegenerative disorders.
The company is composed of a R&D section, a cell culture section, a production section and quality control section and practices according to the GMP, GLP and CE regulations. In the ‘MOODINFLAME’ project, as a sub-coordinating centre for tryptophan biomarkers studies, ApDia will coordinate the quality assurance of the laboratory analyses; establish the external quality assurance scheme for the laboratories participating in tryptophan biomarker assays and quality control, and develop and validate the diagnostic tools for a user-friendly and cost-effective tryptophan biomarker tests to be used in clinical practice.
Affectis is a biopharmaceutical company implementing novel concepts for the treatment of mental disorders, especially depression, schizophrenia, and anxiety. The Company has unique capabilities to discover and develop drugs based on pioneering findings in the field of mental disorders. These drugs address the increasing need for more comprehensive and faster-acting antidepressants with fewer side effects. Affectis started operations in January 2004 as a spin-off from the renowned Max-Planck-Institute of Psychiatry. A strong team of executives and scientists with long-term experience contribute to Affectis’ progress. The Company has obtained an exclusive license to a patent for the second medical use of coxibs for the treatment of psychiatric disorders. Beginning of 2007, it has in-licensed a novel, selective Cox-2 inhibitor. Affectis will develop the compound, named Cimicoxib, as a treatment for depression and schizophrenia. A Phase IIa trial with Cimicoxib in depression will be completed in early 2010.
Newron Pharmaceuticals SpA
Newron Pharmaceuticals is a clinical stage biopharmaceutical company focused on the discovery and development of novel therapies for diseases of the Central Nervous System and pain. It is headquartered in Bresso near Milan, Italy, with fully owned subsidiary in Basel, Switzerland.
The Company currently has two late stage product candidates in development and a pipeline of earlier compounds. Newron is undertaking phase III trials of its lead candidate, safinamide, for the treatment of Parkinson’s disease (PD) in conjunction with its partner, Merck Serono.
Newron is also conducting a pivotal study (SERENA) with ralfinamide in patients with neuropathic low back pain, a disease affecting more than 55m people with no approved drugs on the market. drug discovery programmes are focused on the ion channel target class with new compounds at various stages of preclinical development.
The Newron’s team is comprised of scientific, technical, and senior-level business professionals as well as a strong board of directors with a long experience in multinational big pharma.
The scientific staff has a strong background in electrophysiology, cell biology and in vivo pharmacology.
The Division of Psychopharmacotherapy (Head: Dietrich van Calker) investigates the mechanism of action of medications used in the treatment of psychiatric diseases, in particular mood stabilizers and antidepressants, and the neurobiological underpinnings of these illnesses. Major objectives of research are presently the analysis of the transcription of candidate genes such as components of the cellular signal transduction cascade in peripheral cells of bipolar patients and the regulation of their expression and function in neural cell cultures and in animal models.
The Division of Molecular Psychiatry (Head: Knut Biber) investigates role of microglia in the brain and in particular their function in the resilience against threatening neural damage by injury or overstimulation. To this end the expression, regulation and function of cytokines, chemokines and neurotrophins in microglia and their action on other brain cells is examined in cultured cells and tissue slices and in experimental animals.
Both divisions cooperate in the MOODINFLAME project to elucidate the role of purines (adenosine, ATP, acting as neuro- and gliotransmitters) in the synthesis of neuroimmune mediators such as cytokines and chemokines and in their function in the regulation of the neuron-astrocyte-microglia crosstalk.