Hello!
This Is The Blog For The Resilience Research Community

17-20 September 2018, Hirschegg, Austria

The second PhD and Postdoc Retreat in Hirschegg, Austria, was a great success. 23 PhD students, 6 post-docs, 3 PIs, 6 master’s students, 1 coordinator and 3 guests came together in the beautiful and sunny landscape, lodging in the very friendly Haus Bergkranz to discuss stress resilience and various other scientific themes, and to facilitate networking within the members of CRC 1193.

Two excellent keynote presentations by our guests Professor Stefan Reber from the University Medical Clinic in Ulm, Professor Jörg Bock from the Otto-von-Guericke University in Magdeburg gave new insights into mechanisms underlying stress-induced pathologies, such as inflammation, and epigenetic mechanisms underlying early life stress-induced behavioral alterations, respectively. Due to cancellation of the 3rd keynote speaker, we were lucky that Dr Michael van der Kooij stepped in as a worthy replacement and presented his latest research on stress-induced hyperglycemia.

PhD candidates and post-docs presented their progress during two lively poster sessions. Professor Susanne Gerber and Dr Torfi Sigurdsson (2 PIs of the CRC 1193) and Dr Tina Zimmermann, as an expert from pharma industry, discussed their career choices and potential challenges throughout their education and (non-)academic career. The so-called Unconference was a rather unusual but exciting session where all participants were asked to proactively suggest and lead short sessions of 30 min on topics they were interested in. Thus, we had discussion groups on publishing, translational research, methods, soft skills, reproducibility of research, but also gaming, meditations and yoga. Everybody was enjoying the social events, such as the very passionate and engaging scientific pub quiz, hiking trips through the Kleinwalsertal, a BBQ, and socializing in the evening.

The overall feedback was very positive, and participants will come back to Hirschegg for a third retreat next year.

Thanks also to the organizers Sandra Zurborg & Sabrina Meister, Kathrin Kachel, and the PhD spokespersons Anya Dietrich, Laura Meine, and Katja Schüler.

Cognitive reappraisal is the volitional reinterpretation or reframing of emotional situations with the intention to change their emotional impact. Cognitive reappraisal has long been considered a particularly adaptive form of emotion regulation, based on cross-sectional positive associations with desirable psychosocial outcomes and negative associations with depression, anxiety and other mental health problems. The idea, of course, is that reappraisal is protective because it reduces the negative impact of stressors on mental health. But is that truly the case? In other words, is reappraisal a resilience factor?

In an early cross-sectional study, Troy and colleagues (2010) showed that, in healthy female subjects with a good ability to positively reappraise sad film clips, the well-known relationship between perceived stress from recent negative life events and current depressive symptoms was abolished – a first indication that reappraisal is good for mental health because it protects against the negative influence of stressors. Then, in 2016, Jenness and colleagues reported a similar relationship in prospective-longitudinal data from adolescents exposed to intense media coverage of the 2013 Boston Marathon terror attack. Subjects’ frequency of engaging in reappraisal when challenged, as measured by self report before the attack, moderated the effects of media coverage exposure on PTSD symptoms measured several weeks after the attack.

A new study by Zahniser and Conley (2018) from Loyola University Chicago makes another very strong case. Here is the story: if you enter college with high levels of internalizing symptoms (IS), i.e., anxiety and depression, you are very likely to also have high symptoms at the end of your first college year. Taken. If you find your stress levels to increase from college entry to the end of your first semester (increased perceived stress), this also enhances chances you will have high IS another semester later, at the end of your first year. Thus, an increase in perceived stress early in your college career is something like a stressor in its own right, contributing to deterioration of mental health. Also taken. Comes in cognitive reappraisal, measured here at the end of students’ first semester (midway between the two IS assessments) in the form of a questionnaire looking at how frequently and habitually one uses reappraisal relative to a supposedly maladaptive form of emotion regulation, expressive suppression. The data show: if you are particularly stressed by your first semester (if your increase in perceived stress from college entry to the end of your first semester is high) and if at the same time you frequently use cognitive reappraisal, you are less likely to develop more IS than infrequent reappraisers. In other words, cognitive reappraisal beneficially moderates the negative effects of perceived stress on mental health. The study is remarkable because of its longitudinal design and the large sample of over 1000 volunteers.

Cognitive reappraisal being a resilience factor confirms predictions of positive appraisal style theory of resilience (Kalisch et al., 2015). It will be important to see if the existing longitudinal results extend to other, including to more severely stressed, populations. And also whether the key variable is how often or automatically one uses reappraisal or how effective and efficient one is in regulating one’s emotions by reappraisal. The latter would require experimental tasks along the lines of the Troy et al. study. Two currently ongoing studies (MARP and LORA) by the CRC1193 and the Deutsches Resilienz Zentrum in Mainz (DRZ) will hopefully tell us more.

Recent research on cognitive emotion regulation will also figure prominently among the topics of this year's International Symposium on Resilience Research in Mainz (Sept 26-28).

By Sarah Ayash, Mainz

After arriving at the beautiful venue of ‘Seeon abbey’, participants had the chance to introduce themselves and their research to each other. It became quickly clear that we were a very heterogeneous group in terms of education, research background, and even cultures, adding to the richness of the spring school experience.

We started our first day by an introduction on stress research and on how its accumulated literature can help pave the way for resilience research. The talk was given by Professor Isabelle Ouellet-Morin from the University of Montreal, who focused on the experience of victimisation and its association with indicators of cortisol secretion. However, she also made clear that there is still a need to make sense of the fragmented findings, starting by testing systematically the impact of severity, timing, and chronicity, including potential nonlinear relationships. Genetically informed research designs, looking for processes promoting resilient functions as opposed to the vulnerability framework, and mobilising the knowledge into action are all needed steps for further development.

Our first day ended with a delicious BBQ on the lake, offering the participants and the speakers the chance to network in a friendly atmosphere.

The second day started with a talk by Professor Oliver Tüscher from Deutsches Resilienz Zentrum (DRZ) Mainz, who addressed the issue of not having yet an agreeable conceptual framework for resilience. The talk initiated an interesting discussion between the participants as well as other speakers about how to define resilience (Is it a trait some people are born with and others not? Or is it a learning and memory phenomena? Is it the lack of any reaction to a stressor? Or is it active mechanisms shaping a functional reaction?) Such questions and more triggered deep thoughts and reflection.

From human models in resilience, Professor Ulrich Schmitt from University Medical Centre Mainz picked up the thread and presented the first talk on animal models in general, and mice in particular. The crucial criterion for defining resilience in mice is the ability to avoid some or all of the deleterious behavioural effects following chronic stress. The development of the chronic social defeat model in mice has enabled the examination of stress and, recently, by employing a novel measure of social interaction resulting in a striking heterogeneity in the readout, the robust distinction of stress resilient and non-resilient (socially avoidant) mice. As the large majority of our participants worked on human models, participants were encouraged to make the talk an interactive one, in order to understand the importance and the possibilities of mouse models and eventually to challenge those models in a constructive manner.

As the spring school was intended to be educational, a large proportion of time especially during the second and the third days was dedicated to practical sessions. Participants were asked to split into different groups, each composed of an equal number of human and animal researchers. Each group had to develop a scientific question concerned with resilience and to create the experimental setup for answering this question. Half of the groups had to use an animal model for that, whereas the second half a human model. The groups working on the human model were supervised by Oliver Tuescher and Professor Rajita Sinha from Yale University, whereas the groups working on the animal model were supervised by Ulrich Schmitt and Professor Soojin Ryu (DRZ). Finally, each group had to prepare a presentation for the last day, assessed by the speakers to eventually identify the best group.

Poster sessions spanned three straight days, and each participant had the chance to present his/her poster to an equal number of animal and human researchers. Researchers had to rate each poster according to its content and appearance on a scale of 1 to 5, to eventually award the highest scorer an honorary certificate.

Our second day ended with celebrating differences, with a cultural evening full of bright traditional clothes as well as national beverages and deserts.

The third day started with a talk by Soojin Ryu on zebrafish as an animal model for resilience. Soojin Ryu talked about the advantages of using this animal model to investigate resilience: fast reproduction, relatively easy genetic manipulations, and most importantly a conserved stress response system. However, this model is not devoid of challenges, many of which were discussed during the talk.

Rajita Sinha gave the second talk for the day, which revolved around the clinical question “Can we build brain resilient networks for adaptive coping and primary and secondary disease prevention?” Based on interesting functional magnetic resonance data, the answer seems to be in the direction of yes! But further research is still needed to say this conclusively.

The fourth day was intended to be a day full of talks and discussions. The day started with a talk on the identification of resilience factors in human risk populations by Professor Karin Roelofs from Radboud University Nijmegen, who presented a longitudinal study that followed participants since infancy up to 20 years later. The following talk by Professor Birgit Kleim from the University of Zurich was complementary to the first, by addressing the novel methodological approaches for investigating those resilience factors in humans. Professor Erno Hermans from the Donders Institute for Brain, Cognition, and Behaviour talked about the large-scale neural network dynamics that underly stress and resilience. Finally, Professor Gal Richter-Levin from University of Haifa ended the day with translational approaches to resilience research using rats as an animal model.

So far, our participants were introduced to zebrafish, mice, and rats as animal models. The picture would not be complete without an introduction to the same type of research in non-human primates. To that end, the last talk of the spring school was given by Professor David Lyons from Stanford University. Non-human primate research was not the only novel aspect of the talk. David Lyons also questioned our perception of stress as always being negative. He made us aware of an imbalance in stress research, with the large majority of researchers focusing on its detrimental effects and very few addressing its positive effects, referred to as “post traumatic growth” and “stress inoculation”, both of which build on the conceptual idea that stress resilience is a learning mechanism. This imbalance could be attributed to different reasons. However, one reason David Lyons pointed out recently became apparent in the revelations that the father of stress research, Hans Selye, had been funded by the tobacco industry, providing the industry with arguments that smoking is not the main cause behind various illnesses but stress is and that smoking works as a relaxing agent in stressful situations, thereby having positive health effects. Regardless of the different opinions, the idea was to educate participants to pay attention to the funding sources and not to be naive about conflicts of interest. The talk ended with a long discussion on how the public can be educated on the positive effects of stress, as the final aim of science should be improving lives and further progress of societies.

The last day ended with best poster awards as well as a presentation by the honored working group.

Overall, it was a great experience and indeed an educational one that we hope will become a regular annual event.

Note: The CRC1193, intresa (International Resilience Alliance), Deutsches Resilienz Zentrum (DRZ), and the EU Horizon project DynaMORE thank the organizers Daniel Turner, Jessica Fritz, Anna Gerlicher, Ilya Veer, Martina Diehl and last but not least Sarah Ayash for their great job!

Find infos on

John Cryan, University College Cork
Isaac Galatzer-Levy, Mindstrong Health, Palo Alto
Ethan Kross, University of of Michigan, Ann Arbor
Klaus Lieb, DRZ Mainz
Christopher Lowry, University of Colorado, Boulder
Carmen Morawetz, Free University Berlin
Carla Nasca, Rockefeller University
Stefan Reber, University of Ulm
Soojin Ryu, DRZ Mainz
Mathias V. Schmidt, Max Planck Institute of Psychiatry, Munich
Gal Sheppes, Tel Aviv University
Michael Ungar, Dalhousie University
Michael van der Kooij, DRZ Mainz

at our symposium website (www.drz-mainz.de/symposium)

We have all learned that social support is an important resilience factor. We have also all become aware of the distinction between perceived and objective social support, perceived social support (how you feel supported) being said to actually matter for mental health. Finally, we have learned to distinguish between positive social support (where we are encouraged by others, or feel cared about) and negative social support (your friends or family members making demands, criticizing you, or arguing with you). So, what else could we wish than a) perceived b) positive social support (PPSS)? Sounds like a magic bullet.

Unfortunately, as pointed out by Nickerson et al. in their recent very elegant paper in Psychological Medicine, studies investigating the relationship between PPSS and PTSD symptoms have yielded rather mixed results. If anything, it looks like PTSD symptoms may lead to reductions in PPSS, while there is less evidence that PPSS might protect against the development of PTSD symptoms (i.e., that PPSS is a resilience factor).

To shed light on the issue, Nickerson and colleagues collected a unique prospective-longitudinal data set from injury survivors (N=1150 at study inclusion), who reported on their PTSD symptoms (CAPS) and their PPSS and PNSS (perceived negative social support) immediately as well as 3, 12, 24, and 72 months after the trauma.

These data allowed the authors to ask, among others: does a score on one of the three variables at time point t statistically affect the change in the scores on the other two variables from t to t+1. Meaning, for instance: if I enjoy high PPSS now, is this making it likely my PTSD symptoms will subsequently decrease (a cross-lagged bivariate change)?

The result? Subjects with high PTSD symptoms at t were likelier to perceive their NSS to subsequently increase (more PNSS at t+1 than at t - bad news 1). Such subjects also tended to find their PSS to decrease (less PPSS at t+1 than at t - bad news 2). And: neither PNSS nor PPSS predicted PTSD symptom changes. While it is perhaps relieving to see that negative social support perceptions (PNSS) do not enhance subsequent PTSD symptoms, it is clearly a disappointment for a resilience researcher that perceived positive support (PPSS at t) is not related to PTSD symptom reduction (from t to t+1 - very bad news 3). In other words: positive support perceptions do not protect against post-traumatic symptoms. This questions whether PPSS can be considered a resilience factor.

The authors are careful enough to discuss the limitations of their study, including a sample of subjects having experienced only a specific type of trauma and not living in apparently instable social environments, where social support might play a more important role; the focus on PTSD symptoms as single outcome measure; their lack of information on other potentially important factors, such as offered vs. experienced support, source of support, emotional vs. instrumental support, or moderating personality traits. Hence, the question clearly warrants further research.

Nevertheless, the study by Nickerson et al. reminds us that we should be cautious in the interpretation of cross-sectional associations between assumed resilience factors and mental health outcomes after adversity. After all, the cross-sectional correlation analyses also reported in the paper showed significant negative associations between PPSS and PTSD at all measurement time points (as well as positive associations between PNSS and PTSD). Hence, at first sight, a good reason to conclude that PPSS is a resilience factor. Unfortunately, it is still mostly these types of cross-sectional analyses that most of our information on resilience factors is derived from. The study therefore is a very nice example of the importance to conduct prospective-longitudinal studies in resilience research, as recently highlighted by a large international consortium of authors (Kalisch et al.). The study also highlights the value of advanced statistical methods for the analysis time-variant multivariate data, such as latent difference score (LDS) structural equation modelling used here.

Like every year, speakers at our 3^rdInternational Symposium on Resilience Research (taking place end of September 2017 in Mainz, Germany) showed lots of unpublished data, some of which have meanwhile made it into high-profile journals. One of those data sets, presented by Scott Russo from Mount Sinai, has recently come out in Nature Neuroscience (Menard et al.).

Like many studies on mouse resilience, the study used the Chronic Social Defeat Stress (CSDS) paradigm, in which a mouse is exposed once a day over ten days to the attacks of a much heavier, aggressive “resident” mouse, whose cage it is forced to enter. CSDS induces long-lasting social aversion (reduced social interaction with other, non-aggressive mice) and anhedonia (e.g., reduced sucrose preference) in the intruder mouse, behavioral dysfunctions reminiscent of some of the symptoms of human depression. Hence, CSDS is considered by many an interesting depression model. However, CSDS does induce these dysfunctions in all intruder mice. Already in 2007, Krishan et al. could show in Cell that a substantial fraction of the intruders (the “resilient” ones) show social and reward-related behavior comparable to non-stressed control mice. This finding was probably a key moment for resilience research in rodent models and has since led to many important insights into the neurobiological underpinnings of resilience.

Many of those studies focussed on the brain, but there have also been intriguing findings about a role for the peripheral immune system in resilience (e.g., Hodes et al., in PNAS, 2014). Now, Menard et al. find that CSDS induces loss of expression of the protein claudin 5 (Cldn5) specifically in intruder mice susceptible to the detrimental behavioral long-term effects of CSDS – but not in the resilient mice. Cldn5 lives in tight junctions, the cellular structures that knit together the endothelial cells that line the blood vessels in the brain. Tight junctions are crucial components of the so-called Blood-Brain Barrier (BBB) that keeps molecules from the blood from freely entering the brain. Cldn5 reduction in the present study was mainly observed in blood vessels in the nucleus accumbens (a key region of the reward system, dysfunctions of which have been linked to depression) and was also accompanied by ultrastructural vessel abnormalities and permeability of the BBB in this brain area even for large blood proteins, in susceptible mice. Interestingly, post-mortem patient data indicated a similar loss of Cldn5 in depression.

When the authors knocked down Cldn5 in the accumbens, this exaggerated the effects of a milder variant of social stress into full-blown social aversion and anhedonia, and when Cldn5 expression was allowed to recover in these animals, this also rescued the behavioral deficits. Hence, Cldn5 expression might have a pro-resilience, protective function.

Enters the immune system. The authors (see Hodes et al.) had previously observed a drastic increase in blood levels of the pro-inflammatory cytokine IL-6 after CSDS in susceptible mice. They now extend this finding to IL-6 levels in the accumbens, and they provide evidence that stress-induced accumbal IL-6 is most likely derived from the blood, not produced locally. Downregulation of Cldn5 expression is apparently crucial for allowing the passage of IL-6 into the accumbens. Finally, they show that infusion of IL-6 into the accumbens before a mild variant of social stress is sufficient to induce marked social aversion.

Hence, inflammatory processes play a key pathogenic role in a mouse model of depression, in line with an increasing number of findings of inflammatory processes in depressed patients. For resilience research, the data indicate an important role for an intact Blood-Brain Barrier in protecting against detrimental influences of peripheral inflammatory processes. It will be interesting to see whether future research can identify methods to preserve or repair BBB integrity, which should have preventative effects in chronically stressed individuals.

From a broader perspective, the study is important because it finally provides a bridge between the immune system, whose role in stress-related pathology has aroused much interest in recent years (not least by the work of the Russo lab), and the brain in explaining the effects of chronic stress. This bridge seems to be the vasculature of the accumbens. What this also means is: if it turns out impossible to find ways to dampen peripheral inflammation of entry of cytokines into the accumbens, other ways of protecting or improving accumbal function might as well also help. In any way, the brain is back on center stage.

This blog is a service for the international resilience community by researchers of the DFG-funded Collaborative Research Center CRC 1193 “Neurobiology of Resilience“,  based in Mainz and Frankfurt; the International Resilience Alliance (www.intresa.org); the EU project DynaMORE; and the Deutsches Resilienz Zentrum in Mainz (www.drz.uni-mainz.de). We hope to develop this place into a true virtual home for all those interested in promoting this fascinating  and flourishing field of research.

New blog entries are announced via Twitter (ResilienceResearch@ResilienceRes, #resilience). Follow us and share!

And please comment and discuss with us. Or provide us with news and  information you feel might be interesting for everyone. Suggestions for blog entries  can be sent to rkalisch@uni-mainz.de and will be assessed by the editorial team.

Greetings from the team. And hope to see you again here.

Raffael Kalisch, Beat Lutz, Michèle Wessa, Oliver Tüscher, Klaus Lieb, Marianne B Müller