Kalisch et al., resilience perspective paper, R1 1
1
The resilience framework as a strategy to combat stress-2
related disorders 3
4
5
Raffael Kalisch
1,2
, Dewleen G. Baker
3,4
, Ulrike Basten
5
, Marco P. Boks
6
, George A. 6
Bonanno
7
, Eddie Brummelman
8,9
, Andrea Chmitorz
1,10
, Guillén Fernàndez
11
, Christian J. 7
Fiebach
5,12
, Isaac Galatzer-Levy
13
, Elbert Geuze
6,14
, Sergiu Groppa
1,15
, Isabella 8
Helmreich
1,10
, Talma Hendler
16,17
, Erno J. Hermans
11
, Tanja Jovanovic
18
, Thomas Kubiak
1,19
, 9
Klaus Lieb
1,10
, Beat Lutz
1,20
, Marianne B. Müller
1,10
, Ryan J. Murray
21,22,23
, Caroline M. 10
Nievergelt
3,4
, Andreas Reif
24
, Karin Roelofs
11,25
, Bart P.F. Rutten
26
, David Sander
22,23
, Anita 11
Schick
1,2
, Oliver Tüscher
1,10
, Ilse Van Diest
27
, Anne-Laura van Harmelen
28
, Ilya M. Veer
29
,
12
Eric Vermetten
14,30,31
, Christiaan H. Vinkers
6
, Tor D. Wager
32,33
, Henrik Walter
29,34
, Michèle 13
Wessa
1,35
, Michael Wibral
36
, Birgit Kleim
37
, International Resilience Allliance (intresa)*, DFG 14
Collaborative Research Center CRC1193 “Neurobiology of Resilience”** 15
16
1
Deutsches Resilienz Zentrum (DRZ), University Medical Center of the Johannes Gutenberg 17
University, Mainz, Germany 18
2
Neuroimaging Center (NIC), Focus Program Translational Neuroscience (FTN), Johannes 19
Gutenberg University, Mainz, Germany
20
3
VA Center of Excellence for Stress and Mental Health and VA San Diego Healthcare 21
System, San Diego, United States 22
4
Department of Psychiatry, University of California San Diego, San Diego, United States 23
5
Department of Psychology, Goethe University Frankfurt, Frankfurt am Main, Germany
24
6
University Medical Center Utrecht, Brain Center Rudolf Magnus, Utrecht, The Netherlands 25
7
Department of Counseling and Clinical Psychology, Teachers College, Columbia University, 26
New York, United States 27
8
Department of Psychology, Stanford University, United States
28
9
Research Institute of Child Development and Education, University of Amsterdam, The 29
Netherlands 30
10
Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes 31
Gutenberg University, Mainz, Germany
32
11
Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Centre, 33
Nijmegen, The Netherlands 34
12
IDeA Center for Individual Development and Adaptive Education of Children at Risk, 35
Frankfurt am Main, Germany
36
13
Department of Psychiatry, New York University School of Medicine, New York, United 37
States 38
14
Military Mental Healthcare - Research Centre, Ministry of Defence, The Netherlands 39
15
Department of Neurology, University Medical Center of the Johannes Gutenberg
40
University, Mainz, Germany 41
16
Tel Aviv Center For Brain Functions, Wohl Institute for Advanced Imaging, Tel Aviv 42
Sourasky Medical Center, Israel 43
17
School of Psychological Sciences, Tel Aviv University, Israel
44
18
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 45
Atlanta, United States 46
19
Department of Health Psychology, Institute of Psychology, Johannes Gutenberg University, 47
Mainz, Germany
48
20
Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg 49
University, Mainz, Germany 50
21
Developmental Clinical Psychology Research Unit, Faculty of Psychology and Educational 51
Sciences, University of Geneva, Switzerland
52
22
Laboratory for the study of Emotion Elicitation and Expression (E3 Lab), Department of 53
Psychology, University of Geneva, Switzerland 54
23
Swiss Center for Affective Sciences, University of Geneva, Switzerland 55
24
Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University
56
Hospital Frankfurt, Frankfurt am Main, Germany 57
25
Behavioural Science Institute (BSI), Radboud University, Nijmegen, The Netherlands 58
Kalisch et al., resilience perspective paper, R1 2
26
Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, 59
School for Mental Health and Neuroscience, Maastricht, The Netherlands 60
27
Health Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, 61
Belgium 62
28
Department of Psychiatry, University of Cambridge, United Kingdom 63
29
Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin, Berlin, 64
Germany 65
30
Leiden University Medical Center, Leiden, The Netherlands 66
31
Arq Psychotrauma Research Group Diemen, The Netherlands 67
32
Department of Psychology and Neuroscience, University of Colorado, Boulder, United 68
States 69
33
Institute of Cognitive Science, University of Colorado, Boulder, United States 70
34
Berlin School of Mind and Brain, Humboldt University, Berlin, Germany 71
35
Department of Clinical Psychology and Neuropsychology, Institute of Psychology, 72
Johannes Gutenberg University, Mainz, Germany 73
36
MEG Unit, Brain Imaging Center (BIC), Goethe University Frankfurt, Frankfurt am Main, 74
Germany 75
37
Department of Psychiatry, Psychotherapy and Psychosomatics, University of Zurich, 76
Switzerland 77
78
79
80
Kalisch et al., resilience perspective paper, R1 3
Acknowledgement 81
*Members of intresa: Contributing authors: EB, AC, GF, TH, IH, EH, BK, RK, TK, KL, RJM, 82
AR, KR, DS, AS, OT, IVD, IMV, HW, MWe; Non-author collaborators (supporters not 83
meeting standard ICMJE authorship criteria, but having proof-read and approved the 84
manuscript): Dirk Hermans, Filip Raes, Johan Vlaeyen (all University of Leuven, Belgium) 85
**Members of CRC1193 “Neurobiology of resilience to stress-related mental dysfunction: 86
from understanding mechanisms to improving prevention”, based at Johannes Gutenberg 87
University Mainz, with its University Medical Center, Goethe University Frankfurt, Max 88
Planck Institute for Brain Research Frankfurt, and Institute for Molecular Biology Mainz, 89
Germany: Contributing authors: UB, CJF, SG, KL, BL, MBM, RK, AR, OT, MWe, MWi; Non-90
author collaborators (supporters not meeting standard ICMJE authorship criteria, but having 91
proof-read and approved the manuscript): Benedikt Berninger, Heiko Luhmann, Robert 92
Nitsch, Konstantin Radyushkin, Soojin Ryu, Mathias Schreckenberger, Susann Schweiger, 93
Albrecht Stroh, Ulrich Zechner (all University Medical Center of the Johannes Gutenberg 94
University Mainz), Amparo Acker-Palmer, Sevil Duvarci, Jochen Roeper, Torfi Sigurdsson 95
(all Goethe University), Johannes Letzkus, Erin Schuman (all Max Planck Institute for Brain 96
Research), Vijay Tiwari (Institute for Molecular Biology). CRC1193 is funded by the 97
Deutsche Forschungsgemeinschaft (DFG). 98
In preparing this article, UB was supported by the Deutsche Forschungsgemeinschaft (DFG 99
CRC 1193, subproject C06); GAB by the United States-Israel Binational Science Foundation
100
(project 2013067), David and Maureen O’Connor, and the Rockefeller Foundation (2012-
101
RLC 304); AC by DFG CRC 1193, subproject C04; EB by the European Union's Horizon
102
2020 Programme (EU H2020 /705217); CF by DFG CRC 1193, subprojects C02 and C06,
103
DFG FI 848/5-1, and the European Research Council (ERC-CoG 617891); IG-L by the
104
National Institute of Mental Health (K01MH102415); SG by DFG CRC 1193, subproject B05;
105
EJH by the ERC (ERC-CoG 682591); RK by DFG CRC 1193, subprojects B01 and C01, and
106
the State of Rhineland-Palatinate (project 1080, MARP); KL by DFG CRC 1193, subproject
107
Z03, and the State of Rhineland-Palatinate (project 1080, MARP); BL by DFG CRC 1193,
108
subprojects A02, B03, and Z02; MBM by DFG CRC 1193, subprojects A03 and Z02; RJM by
109
the Swiss National Science Foundation (SNF 100014-143398; project n° un 8306); AR by
110
DFG CRC 1193, subprojects C07 and Z03, and EU H2020/2014-2020 (643051 (MiND) and
111
667302 (CoCA)); KR by the ERC (ERC_StG2012_313749) and the NWO (NWO VICI #453-
112
12-001); BPFR by the NWO (NWO VENI #916-11-086); DS by the SNF (SNF 100014-
113
143398, project n° un 8306); OT by DFG CRC 1193, subproject C04, and the State of
114
Rhineland-Palatinate (project 1080, MARP); ALVH by the Royal Society (DH150176); CHV
115
by the Netherlands Brain Foundation (Fellowship F2013(1)-216) and the NWO (NWO VENI
116
#451-13-001); TDW by the National Institute of Health (NIH); MWe by DFG CRC 1193,
117
subprojects C05 and C07; MWi by DFG CRC 1193, subproject C04.
118
The authors than Anna Kline and Jessica L. Jenness for providing unpublished results.
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Conflict of Interest
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All authors report to have no financial and non-financial actual or perceived competing interests.
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AR has received a research grant from Medice and speakers honoraria from neuraxpharm
123
and Boehringer.
124
HW has received a speakers honorarium from Servier.
125
All other authors report no financial relationships with commercial interests.
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Kalisch et al., resilience perspective paper, R1 4
ABSTRACT
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Consistent failure over the past decades to reduce the high prevalence of stress-
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related disorders has motivated a search for alternative research strategies. Resilience
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refers to the phenomenon that many people maintain mental health despite exposure
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to psychological or physical adversity. Instead of aiming to understand the
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pathophysiology of stress-related disorders, resilience research focuses on protective
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mechanisms that shield people against the development of such disorders and tries to
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exploit its insights to improve treatment and, in particular, disease prevention. To
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fully harness the potential of resilience research, a critical appraisal of the current
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state of the art – in terms of basic concepts and key methods - is needed. We
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highlight challenges to resilience research and make concrete conceptual and
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methodological proposals to improve resilience research. Most importantly, we
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propose to focus research on the dynamic processes of successful adaptation to
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stressors, in prospective longitudinal studies.
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Kalisch et al., resilience perspective paper, R1 5
MAIN TEXT
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Each year, more than half a billion people around the globe suffer from a mental
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disorder such as anxiety, post-traumatic stress disorder (PTSD), depression, or
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addiction that can to some extent be traced back to the influence of exogenous or
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endogenous stressors. Such stressors include traumatic events, challenging life
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circumstances or life transitions, or physical illness (1). Together, stress-related
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disorders in the broadest sense annually cause a hundred million years lived with
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disability (YLD). In 2013, major depression was the second leading cause of
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disability world-wide, while anxiety disorders ranked 9
th
(1). Not only do these
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numbers imply much individual suffering; they also indicate tremendous negative
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consequences for society. In Europe, for instance, the direct and indirect economic
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costs incurred by stress-related conditions have been estimated to be over €200
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billion per year (2).
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The high incidence of stress-related disorders is not new, and a worrying aspect of
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the epidemiological findings is that there has, on average, been no relevant decrease
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in numbers over the past decades (1). This is despite huge efforts spent on
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investigating the pathophysiology of these disorders and despite remarkable
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successes that have been made in understanding disease mechanisms and in
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developing effective treatments. A recent survey that attempted to identify reasons
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for the failure to reduce disease prevalence found that the lack of improvement can
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neither be attributed to an increase in risk factors, i.e., stressors, nor to greater public
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awareness of mental disorders or greater willingness to disclose (3). More likely
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reasons are that the provided treatments frequently do not meet minimal quality
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criteria (“quality gap”) and that there are virtually no attempts to prevent disorders
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(“prevention gap”). In the four English-speaking countries included in the study,
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resources allocated to prevention and prevention research were found to be very
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small, and prevention efforts were somewhat provocatively characterized by the
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authors as “piecemeal” (3).
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Resilience research as an alternative strategy to promote mental health
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We here argue that resilience research is a promising strategy to help close the
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prevention gap and thereby to complement traditional disorder-focused research. The
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science of resilience is based on the well-documented observation that many people
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maintain mental health despite exposure to severe psychological or physical
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adversity - a pattern that has been observed across different populations and types of
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adversities (4–6). Resilience research aims to understand why some people do not, or
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only temporarily, develop stress-related mental dysfunction, in spite of being subject
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to the same kind of challenges that cause long-term dysfunction in other people. This
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approach is naturally linked to the question of how to prevent stress-related
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disorders, rather than attempting to treat them at a later stage when significant
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individual suffering and societal and economic costs have already occurred (7).
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Resilience research, thus, is effectively a paradigm shift away from disease-focused
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towards health-focused research and from investigating pathophysiology towards
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investigating the mechanisms that can protect individuals against stress-related
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disease.
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We therefore posit that resilience research is an important, or even necessary,
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complement to traditional pathophysiological research and has great potential for
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improving public health. We have reason to believe that this view is shared by many
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