GRADUATESCHOOL of LIFE SCIENCES
content Introduction 4 Introduction prof. E.R. de Kloet
History of BIC
Committee of Advice and Recommendation
Prof. dr. Stafford Lightman
Prof. dr. Ruut Veenhoven
Dr. Onno Meijer
Dr. Harm Krugers
Hans van Maanen
Prof. dr. Paul Lucassen
Dr. Erno Hermans
Mitzy Kennis, MSc
Marc Molendijk, MSc
Dear guest, Welcome to the Biomedical Interfacultary Congress (BIC) 2014 about Stress-Related Disorders! We open the day by introducing you to two influential individuals in the field of Stress-Related Disorders. First of all, prof. dr. Stafford Lightman will give a seminar about stress hormone regulation in the brain. He is an expert in this field as he is head of the Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology. Lightman’s lecture will provide you with a basic biomedical conception of stress. Second, prof. dr. Ruut Veenhoven, alias ‘godfather of happiness studies’, is going to introduce us to the terms of human happiness. Both gentlemen represent a different point of view in the field of stress related research, which makes this congress quite valuable in my opinion. The mixture of contrasting perspectives is the guideline of the day. The first parallel session is composed of lectures about mental and fundamental bases of stress. The second parallel session consists of a workshop, a lecture of a down-to-earth 4
outlook on stress and lectures about stress from a more clinical perspective. Finally, the contrasting perspectives are gathered in the career market, where present and future – study and work – mingle. BIC 2014 will be concluded with a debate about stress and I cordially invite you to have a drink with us or one of the companies at the end of the day. The first drink is on us! Last but not least, I would like to thank the Committee of Advice and Recommendation and our sponsors for their cooperation and their confidence in BIC 2014. BIC minds have no time for worries! Sincerely, Sophia van Ghesel Grothe Chairman BIC 2014
introduction prof. E.R. de Kloet Welcome and wonderful that you participate today in de 8th edition of the ‘Biomedische Interfacultair Congres’ about stress-related disorders! Indeed stress affects everyone. Stress is essential for life and for adaptation to a changing world. Stress helps you to cope with difficult situations and is preparing you for the future. As its discoverer said “Stress is the spice of Life”. Yet you are told that work stress and uncertainty increase vulnerability for disease. How is this possible that the action of stress and stress hormones can change from protective to harmful? This cardinal question is at the heart of BIC 2014. In two plenary lectures stress is considered from two totally different angles. Is the first lecture focused on the science of regulation and function of the neuroendocrine system, the second one highlights a real human aspect: happiness. Subsequently, two parallel sessions are dedicated to a deeper understanding of the function of the stress response in emotion and cognition during health and disease from genes to the whole organism. How can stress hormones program baby brains for later life? Are these hormones important for healthy ageing? Is there
a future for an anti- or pro-stress medicine? These and other questions will be discussed for sure in a tough final debate with an audience of brand-new stress experts. On behalf of the congress committee I wish you an inspiring day full of happiness. Ron de Kloet
Em. Professor of Medical Pharmacology, University of Leiden, LUMC Committee of advice and recommendation
Sophia van Ghesel Grothe Chairman
Romy Meier Public Relations
Anouk Verboven Secretary
Merlin Weeda Supporting Member
Coen Mulders Treasurer
Ernst Bank Supporting Member
Marit Melssen Program
Gittan Blezer Supporting Member
Iris Pijtak Logistics
Nienke Koopman Supporting Member
Olga Buslenko Sponsors
history of bic
The first Biomedical Interfacultary Congress was held on May 13, 2000 in Leiden and was organized by the Medical Faculty Society, M.F.L.S. The focus was to present the diversity within the (bio)medical field and specialisms within the different (bio) medical professions to medical students from all over the Netherlands. The second congress was also held in Leiden and was presented with a theme for the first time: ‘Welcome to your Future’. Other universities were involved as well in the organization in order to create a diverse audience. In 2004, the board was officially extended with members from other universities, namely M.B.V. Mebiose (Utrecht University) and MIK punt (University of Amsterdam).
In 2010, the board was enlarged with study associations Gyrinus Natans (VU University) and Soos (Nijmegen University). That year, BIC was held in Leiden with the theme: ‘BIC: start of the future’. In the course of time, BIC grew to be a congress for students in Biomedical Sciences and related studies in the Netherlands, and in 2012 the board consisted of members from Amsterdam, Leiden and Utrecht. That year the congress took place once again at VU University Amsterdam.
In 2006, the interfacultairy character was truly honoured and BIC was hosted by M.B.V. Mebiose in Utrecht. Study association Congo (University of Amsterdam) was involved in that edition of the congress for the first time. In 2008, BIC was held at the VU University in Amsterdam, with yet another theme: ‘Big, bigger, BIC: how big do you want to become’. 7
Committee of Advice and Recommendation Prof. Dr. P.R. B채r (UU) School Director of Biomedical Sciences, Utrecht University en vice-chairman of the Graduate School of Life Sciences
Prof. Dr. Paul Lucassen (UvA) Professor of Structural and Functional Plasticity of the Nervous System at Swammerdam Institute for Life Sciences
Prof. Dr. Sabine Spijker (VU) Endowed professor on the Fenna Diemer-Lindeboom chair and team leader at the Center for Neurogenomics and Cognitive Research
Prof. Dr. E.R. de Kloet (LUMC) Professor Medical Farmacology, academic professor at Leiden University and Leiden University Medical Center.
Prof. Dr. Bauke Oudega (VU) Former Dean Faculty of Earth and Life Sciences VU University Prof. Dr. Stanley Brul (UvA) Director Biomedical Sciences (FNWIAMC) and head of the department Molecular Biology & Microbial Food Safety
Prof.dr. P.C.W. Hogendoorn (LUMC) Dean Leids Universitair Medisch Centrum, professor of pathology at the Leiden University Medical Center
09.45 - 10.15
Registration and Introduction
10.15 - 11.15
Keynote speaker 1
Stafford Lightman (UK)
Foyer laag 0 Keynote speaker 2
Lunch break 13.00-14.10
Roze Foyer laag 0
Parallel session 1 Onno Meijer
Harm Krugers Hans van Maanen
Paul Lucassen 14.15 - 15.25
Parallel session 2 Erno Hermans
ZonMw Mitzy Kennis
Marc Molendijk 16.00-17.00
Drinks and Career market
Foyer laag 0
Prof. dr. Stafford Lightman University of Bristol, United Kingdom
Biomedical concepts of stress major stressful activation of the HPA, The hypothalamic-pituitary-adrenal there is a marked remodelling of the (HPA) axis is critical for life. It has pituitary-adrenal interaction. In man a circadian rhythm that anticipates we have looked at pituitary-adrenal the metabolic and cognitive needs dynamics during coronary artery of the active portion of the day, and grafting both “on” and “off” bypass. retains an ability to react rapidly The link between ACTH and glucoto perceived stressful stimuli. The corticoid pulses is maintained but circadian variation in glucocorticoids there is a massive increase in the is very ‘noisy’ as it is made up from adrenal responsiveness to the ACTH an underlying approximately hourly signals. We have now gone on to ultradian rhythm of glucocorticoid look at the mechanisms underlying pulses which increase in amplitude this sensitisation using an experiat the peak of circadian secretion. mental model. We have shown that these pulses emerge as a consequence of the feedforward:feedback relationship between the actions of ACTH on the adrenal cortex and endogenous glucocorticoid on pituitary corticotrophs. The adrenal gland itself has adapted to respond preferentially to a digital signal of ACTH and has its own feedforward:feedback system which effectively amplifies the pulsatile characteristics of the incoming signal. Glucocorticoid receptor signalling in the body is also adapted to respond in a tissue specific manner to oscillating signals of glucocorticoids, and gene transcriptional and behavioural responses depend on the pattern – constant or pulsatile – of glucocorticoid presentation. During 12
Prof. dr. Ruut Veenhoven Erasmus University Rotterdam
Hapiness and stress Stress is often seen as antithetical to happiness, both in the public discourse and in academic writings. In the public discourse stress is typically seen as external ‘pressure’, in particular social pressures, such as for success. In that context the ‘rat race’ and ‘time stress’ are seen to lower happiness in modern society. Yet contrary to such critical views, people appear to be quite happy in nations where market competition prevails and the pace of life is high. In the scientific community stress is rather seen as an internal state of mobilization, sometimes called ‘general adaptation syndrome’. That kind of stress is also seen to work out negatively on happiness. The state itself is indeed unpleasant at the moment, but on the longer term stress can work out positively on happiness, such as by learning. Avoidance of stress will not make for a happy life, the point is to avoid chronic stress.
Dr.Onno Meijer O.C. Meijer, Dept Endocrinology, Leiden University Medical Center, Leiden, The Netherlands
In praise of hormones: stress adaptation from head to toe â€˜Stressâ€™ is a state that we (and other animals) enter when we face demands that go beyond usual homeostatic conditions. A number of neurotransmitters and hormones act to induce and control this state, including brain corticotropin releasings factor, the adrenergic mediators of the sympathetic nervous system, and the adrenal cortex hormone cortisol. As any organ can be involved as either the cause or as the solution of stress, receptors for these mediators are found everywhere in the body. This ensures both optimal capacity for adaptation, but also confers vulnerability to excess stress hormone exposure. The receptors for stress mediators steer a cellular response. Cortisol receptors (of which there are only two types) bind to thousands of loci in the genome to change expression of target genes. Remarkably, there seems to be very modest overlap in the target genes between different cell types. Yet, somehow the genome-wide changes that occur in all these cell types make up an adaptive response to stressors. The data presented in the talk will illustrate 14
how the two types of cortisol receptors can achieve such a sophisticated diversity of action, and how we may use this diversity to influence stress responses in case they turn out to be not so adaptive.
dr. Harm Krugers Stress, memory and vulnerability
Stress is believed to have negative consequences for individuals: â€œpeople suffer from stressâ€?. However, is that negative reputation correct? Emotionally arousing and stressful experiences are remembered well in general. From the evolutionary point of view this is highly beneficial: it is important to acquire and remember important information which enables adaptation to comparable situations in the future. In some individuals however these memories are vividly and inappropriately expressed, such as seen in post-traumatic stress disorder (PTSD). In addition, stress is an important risk factor for depression. The interaction between genes and environment is important for the vulnerability to develop stress-related psychopathology. In this lecture I will discuss show stress affects the brain and in particular memory formation. How does stress enhance memory? Why do some individuals remember (fearful) events better than others? Do experiences during the early postnatal period affect brain structure and brain function? Does this impact memory formation?
Hans van Maanen Care and feeding of science journalists
Many scientists cannot help but mistrust journalists and newspapers. Like the famous saying goes: ‘I believe everything the press writes, except when it’s about my own field of expertise.’ There are many good reasons to be wary of the media, but it cannot be too difficult for a scientist to understand what they do, why they do it, and what they want. In this talk, I will try to give some examples of science communication gone wrong and done right. Journalists are always very eager to hear something really new, they are not so easily fooled - at least not all of them, all of the time. A bit like fellow scientists, really.
PROf. DR. PAuL LuCA SSEn Effects of early life stress and nutrition on later brain plasticity
Exposure to stress during early life (ELS) is associated with an increased vulnerability to develop psychopathology and with lasting cognitive impairments later in life. The underlying mechanisms, however, remains unclear. A potent early-life stressor for the offspring is a deficit in the parent-offspring relationship. This relationship comprises several neurobiological components. A first component of the quality of maternal care is the extent of sensory stimulation, i.e. the amount of licking and grooming a pup receives from its mother. This already influences important parameters of later brain plasticity in a lasting manner. In addition, powerful corticosteroid hormones are released when the mother is stressed that can be transmitted to her pups via her milk, where they can lastingly modulate brain development and behavior of the pup. For instance, neurogenesis, i.e. the birth of new neurons in the adult hippocampus, is reduced by stress and correlates well with the performance in hippocampal dependent cognitive tasks. In addition to these components, also early nutrition is important in â€˜programmingâ€™ the brain and mediating effects of ELS. Both quantity and
quality/composition of the mother milk are important elements while also epigenetic processes have been implicated in maintaining lasting effects of ELS. Thus, determining to what extent sensory stimuli, stress hormones, nutrition and epigenetic mechanisms interact and how they contribute to the lasting effects of ELS on later brain structure and function, is critical for our understanding of optimalâ€™ early life conditions as well as for developing possible (nutritional) intervention strategies.
Dr. Erno Hermans The brain under stress: dynamic shifts in large-scale brain network function in response to acute stress
How does acute stress affect brain function? The standard view in human research has been that acute stress has a detrimental effect: it impairs our ability to think clearly. However, recent findings from animal research paint a more complex picture: stress-related neuromodulators released during stressful experiences exert spatially and temporally specific effects on neural excitability and plasticity. I will argue that these changes trigger comprehensive, brain-wide shifts in neural functioning and enable us to reallocate neural resources according to environmental demands. I will present a model of how stress-sensitive neuromodulatory systems dynamically balance activity across two distinct large-scale neural systems that support attentional vigilance and executive control, respectively. Finally, I will show how this model explains conflicting findings reported in human studies into stress and cognition
Progress requires research and development. ZonMw funds health research and stimulates use of the knowledge developed to help improve health and healthcare in the Netherlands. ZonMwâ€™s main commissioning organisations are the Ministry of Health, Welfare and Sport and the Netherlands Organisation for Scientific Research. In our view, two things are needed to improve health and healthcare in the Netherlands: knowledge, and actual use of knowledge. With a range of grant programmes, ZonMw stimulates the entire innovation cycle, from fundamental research to the implementation of new treatments, preventive interventions and improvements to the structure of healthcare. In selecting grant proposals, ZonMw always looks for a combination of innovation and quality, since this is the only way to deal with the complex challenges we face in society today, and ensure that clients receive affordable care of a high standard. ZonMw always strives for the best result. Workshop During the workshop, all ins and outs about scientific funding and grant application will be mentioned. What 20
can you expect from an organisation like ZonMw? What are the opportunities for an internship? How does an average day at the ZonMw office look like? Next to the answers on these questions, we will discuss some topics about the research landscape in the Netherlands. We hope to welcome you at our workshop. Feel free to ask questions, or visit us at the information market.
Mitz y Kennis, MSc Treatment effects on neural networks in posttraumatic stress disorder (PTSD)
Exposure to severe stress can induce psychiatric disorders such as posttraumatic stress disorder (PTSD). During deployment to war zones soldiers are frequently exposed to potential traumatic events and are therefore at risk for developing PTSD. PTSD is characterized by re-experiencing symptoms, avoiding reminders of the traumatic event, emotional numbing, and hyper arousal. With structural and functional magnetic resonance imaging (MRI) brain abnormalities have been demonstrated in PTSD in the hippocampus, amygdala and prefrontal cortex. Little is known about the effect of treatment on the neurobiology of PTSD. Recent findings indicate that there are some stable neural markers of PTSD, such as ACC volume, and that other brain abnormalities recover, such as the hyperactivation of the amygdala. However, it is yet uncertain whether or not (structural and functional) neural network alterations recover after successful treatment. Novel findings on treatment effects on the emotional brain circuit in PTSD will be presented from the BETTER study protocol, investigating veterans with and without PTSD before and after treatment. 21
Marc Molendijk, MSc Stress/trauma, depression and the neurotrophin hypothesis
Stress- and trauma exposure are intrinsically related to the pathophysiology of mood disorders. Numerous hypothesis have been formulated aiming to explain this evident relation but none of these are satisfactory for a 100 percent. Back in 1997, the neurotrophin hypothesis of depression has been formulated towards this end. It states that pathological conditions such as depression may (partly) be secondary to a stress-induced altered expression of Brain-Derived Neurotrophic Factor (BDNF), a regulator of neuronal plasticity and integrity. This hypothesis has offered a rich framework to study the psychopathology of depression and a number of pre-clinical findings have emerged that clearly favor its predictions. Studies on human subjects, however, present a less clear picture and the translation of this promising hypothesis into human depression and clinical utility has proven to be difficult. In my talk I will first present the state of the art literature (both pre-clinical and clinical) on the relation between stress/trauma exposure and depression-like behavior/mood disorders. After this I want to critically evaluate the correspondence between 22
pre-clinical and clinical findings, with a specific emphasize on psychological functioning in relation to stress/trauma exposure and the neurotrophin hypothesis of depression. A final discussion will balance and close the talk.
Graduate School of Life Sciences, Utrecht University Â Â Scientific Volume Imaging ZonMw Faculty of Science, University of Amsterdam Faculty of Earth and Life Sciences, VU University Amsterdam Departement of Biochemistry and Cell Biology, Utrecht University UMC Utrecht Hersencentrum Biomedisch Studenten Overleg (BMSO) Landelijk Overleg Biologie Studenten (LOBS)
Note: The debate will be in Dutch and therefore the propositions that will be discussed are also mentioned in Dutch in this booklet. Stelling 1 – Stress is goed Zoals Professor de Kloet al aanhaalde in zijn introductie is stress essentieel voor leven. Stress helpt je omgaan met moeilijke situaties en bereid je voor op de toekomst. Toch gaat stress ook gepaard met een verhoogde vatbaarheid voor ziekte en kan het dus slecht zijn voor de gezondheid. Wat is uiteindelijk het eindoordeel; is stress goed of slecht, dat is de vraag. Stelling: Stress is goed. Stelling 2 – Financiering van PhD Vele afgestudeerde Biomedische wetenschappers starten hun loopbaan met een promotietraject. De markt wordt dunner en niet altijd is het mogelijk een promotieplek te vinden die volledig naar je eigen smaak is. Een probleem hierbij is vooral de financiering. Om er voor te zorgen dat de PhD’s in Nederland gemotiveerd blijven, is het belangrijk dat zij zelf achter hun financiering moeten aangaan om het onderzoek dat zij willen uitvoeren te kunnen financieren. 24
Stelling: Een promovendus moet zelf de financiering voor het PhD-traject regelen. Stelling 3 –Biologische factoren bij misdaad Tijdens stressvolle situaties zal ieder mens op zijn eigen manier de afweging maken tussen goed en kwaad. Echter deze manier zal bij personen met bepaalde biologische factoren meer richting kwaad zijn dan bij anderen. Hierbij kan gedacht worden aan personen die vatbaarder zijn voor post-traumatic stress disorder (PTSD). Als deze personen in een stressvolle situatie komen herinneringen opwekt kan er kortsluiting ontstaan in hun hersenen wat tot onverwachte en niet bedoelde reacties kan leiden. Personen zonder deze biologische kenmerken zullen minder snel last van hebben. De vraag is of er hierom verzachtende omstandigheden zouden moeten gelden voor deze personen. Stelling: Biologische kenmerken moeten meegenomen worden in het proces van misdadigers.
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