 Good afternoon, ladies and gentlemen. Thank you, Mr. Chairman. Our brains, ladies and gentlemen, do not seem to be optimally designed for living in the densely populated metropolises of our world. It's quite plausible to all of us that urbanization is associated with increased stress exposure, and it also does not need many explanations to understand that stress can have an impact on our health and on our lives. Yet, and however, it's also clear that and shown that urban populations do, in average, live under improved conditions. They are wealthier, have better sanitation, better contraception, and generally, better general healthcare. So what is stress? Let's clarify some facts. Stress is an unspecific, physiological, and psychological response of the organism to a challenge lying ahead of us, and it is enormously impactful on our well-being. The World Health Organization has declared stress to be one of the major health challenges of the 21st century. But how, and that's a major question, how does stress, and particularly, urban stress get under the skin? How does it get virulent, and how can we prevent stress-associated mental ill health in the urban population? The stress response is modulated by a variety of factors, such as our personality traits and subsequent stress coping strategies, our genes, the responsibility of our stress hormone system, but also our living and upbringing conditions, such as whether we were raised or live in urban, or in rural environment. City living has long been known, at least in psychiatry, to be a risk factor for some major psychiatric diseases. The risk of schizophrenia is about twice as high in cities with a dose-response relationship, both for the amount of time grown up in cities, but also for the size of the city we currently live in. A Dutch group has recently shown in a meta-analysis, was the first meta-analysis of that sort ever made, that the pooled urban prevalence rate for common mental disorders was higher in urban areas compared with rural environments, as for example, with a 39% higher risk for mood disorders, as for example, depression for urban dwellers. But interestingly, no difference for the prevalence of substance abuse disorders between rural and urban. I've been asked this several times today. The effect remains stable even after controlling for important confounders indicating that the difference we see here are only partly explained by population characteristics. This is important evidence pointing to what is called the causation hypothesis that states that urbanicity increases the risk of mental ill health as opposed to the selection hypothesis, which states that high-risk individuals rather seek urban environments. But that does still not mean that city living is harmful per se. Let me make this very clear. It rather means that living urban or not interacts with other risk factors such as, for example, a genetic risk for mental disorders. It has recently been published to give you an example in nature that city living is a factor with a similar effect as cannabis consumption in individual with a high genetic risk for schizophrenia. Studies have also shown that the risk for schizophrenia changes if we move from an urban to a rural environment or the other way around. Now, urbanicity rather represents proxy, which for a stress-related mediator which requires further identification and research. So what is particularly stressing in urban environments? From neuroscience, we know that social stress is the most powerful stressor as far as mental illnesses are concerned. And that feeds out of these, basically out of these two sources, social density and the stress that brings about and social isolation. Social density can mean a constant threat for the social order we live in, overcrowding, that's well shown, can induce stress and illnesses in many species ranging from insects to rodents to primates and also to humans. Social isolation is associated with excess mortality and is presented in this meta-analysis even stronger than smoking, than obesity, or than alcohol. So is it increased stress exposure in crowded urban environments that drives us crazy when the environment becomes less controllable for us? A recent study from Germany, from my colleague Andreas Meyer-Lindenberg from Mannheim nicely contributed to understanding stress as a significant mediator. The authors used functional magnetic resonance imaging to investigate the specific human areas that are affected by stress and urban living. Participants had lived or currently lived in rural areas in small cities or in larger cities. The authors measured regional brain activity while participants performed a social stress task that meant solving heart arithmetic problems with constant negative feedback by the experimenter. Of the activated brain regions, two were of particular interest which are important in the context of stress and emotions. Activation in the amygdala, this is a region which signals negative environmental and environmental threat, correlated with the size of the city which the individual currently resided. And activation of the singulate cortex, that's another region which plays an important role in the limbic system for our stress regulation, correlated with how long a participant had lived in a large city during childhood. And interestingly, urban upbringing also affected the functional coupling between these two areas which meant that those who had spent larger amounts of time in large cities showed a reduced functional coupling of these two brain areas that I just showed. So what is the consequence for stress research and I'm coming to my conclusions. First of all, I want to say that the readout of this and other studies do not suggest that cities or mega cities cause mental problems per se, not at all. We should be really aware of that. It rather shows that city living affects stress issue, associated emotional processing and that can have a risk for those people that carry an increased risk, for example, in the form of a genetic risk for mental diseases. And we urgently need to know more about these inter-individual differences in the context of city living. We need also more information about the specifics of the different stressors, the different degrees of stressors within the urban context, and by which means they translate into brain disorders. And we need to increase our understanding, of course, about the stress protective factors in cities. And certainly we need to know much more about the long-term effects of urban stressors on the developing brain during childhood and which living conditions put the kids at risk. On the action side, three points. Firstly, I would say, as far as we would now base on our neuroscientific knowledge, minimize experience of density in cities, but provide opportunities for social contexts in order to reduce stress vulnerability. But also minimize social isolation, especially in those who have a higher risk for mental ill health. And finally, and probably most importantly, provide information to the population, provide information on stress and stress recovery strategies for urban dwellers just as we provide information about the negative effects of smoking in order to increase awareness and preventative behavior. And just let me add one personal slide that I put together today after different conversations. I think we should and we must move towards a new neurourbanism. What does that mean? It means further exchange between urban planning and architecture on the one side and neuroscience psychiatry on the other to investigate the neurobiological impact of the different modes of today's city living. And what we urgently need to know is to identify the right metrics to see what is stressful, what is not stressful, and what is stress protective. And also we psychiatrists need much more understanding on the strategies, on the options and limits of shaping our environments as we know that mental health is a product of gene environment or inner-factor biological factors and environment interaction. That's enormously important with regard to preventative strategies. And for architects and city planners, it could be useful or helpful or an idea to use some of the methodology that neuroscience has already developed to assess the health impact, the stress impact, and the quality of life and housing and urban planning. Thank you very much for your attention. Thank you.