Stress-related psychiatric disorders across the life span

• Research programme: Stress-related psychiatric disorders across the life span
• Department: Psychiatry
• Programme leader: Prof. Dr. A.M. van Hemert
• Principal investigators: Prof. Dr. R.C. van der Mast, Prof. Dr. N.J. van der Wee, Prof. Dr. R.R.J.M. Vermeiren, Prof Dr. E.E. van Furth, Prof. Dr. J.M.A. van Gerven

Aim and focus

The aim of our research is to better understand the onset and continuity of stress-related psychiatric disorders across the life span and to translate our findings into  personalised treatment and prevention for our patients and their families. 

As a general background for our research we assume that the broad categories of mood- and anxiety-related and disruptive disorders share a dysregulation of  psychobiological stress-regulation systems.  The capacity to adapt to psychological stressors shows a considerable variation from one person to another. This is partly due to skills and experiences that are acquired in a caring and structured upbringing and partly due to biological vulnerability or resilience of the stress-regulation systems. Disorders that are commonly considered separately in the DSM- and ICD-classification systems are likely to share similar dysregulations. 

In our programme we focus on this group of “stress-related disorders”, which include mood (depressive and bipolar), anxiety, and somatoform disorders, trauma and stressor related disorders, obsessive-compulsive disorders, eating disorders and severe behaviour disorders in children. We study these disorders across the life span from early adolescence into adulthood and old age. Over the lifespan, different disorders from this stress-related spectrum may alternate within the same person, shifting from behaviour disorders in early adolescence towards alternating affective and anxiety disorders in adulthood and sometimes mainly apathy in old age. In addition to frequent co-morbidity, there is considerable overlap in treatment approaches between these disorders and often simultaneous improvement. 

In our Centre for Mood and Anxiety disorders, we connect clinical and neurobiological research with top clinical care. We share working alliances in clinical research with the Regional Mental Health providers Rivierduinen, Parnassia  and Curium-LUMC. In these clinical settings we develop and apply techniques of Routine Outcome Monitoring to evaluate and improve personalised patient care. 

In the Centre for Child and Youth Psychiatry, we focus on the early identification of stress related disorders within community mental health centres and (forensic) youth care centres, in order to optimise referral and accurate personalised intervention. We are partner in the regional Academic Workplace SAMEN (‘Together’) and Risk Youth. Next, the Centre focusses on monitoring outcome and improving personalised patient care in specialist child mental health services, which is done in close collaboration with the Knowledge center Child and Adolescent Psychiatry (Kenniscentrum Kinder- en Jeugdpsychiatrie) and other child mental health institutes as part of the e-KJP (expert network Child and Adolescent Psychiatry.

In our neurobiological research, we aim to elucidate the shared biological underpinnings of vulnerability and resilience for stress and “trauma” related psychiatric disorders, using a translational and multidisciplinary lifespan approach. To translate fundamental findings into personalised approaches, we collaborate locally with various groups in the LUMC profile area ‘Translational Neuroscience’ , Biomedical imaging and in the university profile areas ‘Brain function and dysfunction across the life span’ and ‘Health, prevention and the human life cycle’. 

In our Centre for Neuropsychiatry and Ageing, we focus on research and clinic of stress-related psychiatric disorders and the complex relation between ageing, the brain, circulation, neurodegeneration , and psychopathology. Aetiology and manifestations of stress related psychiatric disorders at old age are particularly influenced by age related characteristics such as incident neurodegenerative and cerebrovascular diseases, other somatic morbidity, functional decline and social isolation. The Centre is affiliated to the LUMC Profile Area ‘Ageing’ and the Leyden Academy for Vitality and Ageing (LAVA). 

Position in international context

Partnership in research is increasingly important to address tomorrow’s research questions and for state-of-the-art strategies involving larger and deep (endo)phenotyped samples. Our transdiagnostic approach has a strong international alignment as is illustrated by the Research Domain Criteria (RDOC) strategy that has been developed by the National Institute of Mental Health and by the European Roadmap for Mental Health (ROAMER) initiatives. We are in a strong position to remain competitive in this new international context, based on our local strengths and potential, and on our national and international research collaborations.  We maintain strong and longstanding collaborations with other expert groups in Amsterdam and Groningen in the internationally renowned NESDA-consortium (www.nesda.nl).  Also, LUMC psychiatry is partner in or coordinator of a number of international research networks, including the world-wide Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) initiative (enigma.ini.usc.edu), the European College of Neuropsychopharmacology (ECNP) research networks ( www.ecnp.eu/initiatives) and  innovative research projects like the EU Innovative Medicine Initiative  Psychiatric Ratings using Intermediate Markers (PRISM) (www.imi.europa.eu/content/prism). Child Psychiatry is part of an international research Network InForSANA on clinical assessment of conduct disordered youth in juvenile justice institutes. Related to work on disruptive behaviour disorders, Olivier Colins has an appointment at the Orebro University, Sweden. Further, the biobank is part of a international genetic consortium as part of the FP7 ACTION project.

Content / highlights / achievements

Collecting pertinent data for psychiatric research is a major challenge. Access to sufficient numbers of patients and the collection of valid data on symptoms, relevant characteristics and outcome can be extremely cumbersome. One of our pivotal achievements has been that together with the psychiatry departments of VUMC Amsterdam (VUMC) and Groningen (UMCG) we have created a national collaboration in a research infrastructure, that allows for the accumulation of a number of large and well defined patient cohorts that are used to realize our research aims. NESDA includes 2981 adults with depressive and anxiety disorders (www.nesda.nl), NESDO includes 510 subject with similar disorders at old age (www.nesdo.nl) and NOCDA aims at obsessive-compulsive disorders. We supplement this strategy with the collection of Routine Outcome Monitoring (ROM) in clinical care both in adult and in child and adolescent psychiatry. Our ROM-database is supplemented with a biobank, the MASH-bank, which includes cortisol and DNA material. This combined approach of research and clinical data has been very actively exploited to explore our research themes, together with our partners in Amsterdam and Groningen. In the period 2011 – 2016 the NESDA-study alone resulted already in more than 400 papers in peer reviewed journals. 

Our findings in both in the clinical studies and in the genetic and neuroimaging studies confirm the importance of shared aetiological mechanisms between the major psychiatric disorders. Vulnerability for stress-related psychiatric disorders may have common roots in neurodevelopmental differences. In line with the growing evidence in this respect is a recent study where we could demonstrate that the number of repeats in patients with Huntington’s disease is correlated to depressive disorders, also in the subclinical range of repeats.

Furthermore, the major role of early adverse events and trauma in the stress related disorders across the life span has been clearly demonstrated in a multitude of complementary findings in clinical, neuroendocrinology and neuroimaging studies. Data suggest that genetic vulnerabilities interact with (early) adverse events to produce a life-long vulnerability to the stress-related psychiatric disorders. These findings fit well with detrimental effects on brain structures and emotion regulation we observed in patients with Cushing’s disease. 

Our findings from fundamental studies fit well with the clinical studies that demonstrate the frequent co-morbidity and the general protractive course of the stress-related disorders. These finding are of major importance for the development of clinical interventions, as effort should not only be directed towards cure of symptoms, but also towards dealing with the lifelong vulnerabilities that some of our patients will have to face.

In 2016 the research programme of the department of psychiatry merged with the programme of the department of Adolescent and Child Psychiatry. The two departments already shared a similar approach in studying stress related psychiatric disorders. The merge allows for further alignment of research topics towards the future.

Future themes

We will continue and extent our general strategy of collecting detailed clinical and biological data in shared cohort studies. Together with the Parnassia Groep and Erasmus University Rotterdam, and with support of the Cella Durksz foundation, we recently started data collection for patients with first episode bipolar disorders (www.bincostudie.nl). We intent to continue the successful NESDA-cohort, including innovative biological measures (e.g. microbiome) and to extent the approach to siblings and offspring of patients. Together with the new head of the Erasmus child psychiatry department (Manon Hillegers), the department of Child Psychiatry is developing studies on the use of new technologies in clinical populations. 

We will complement our strategy of the more fundamental genetic, neuroimaging and neuroendocrinological studies with personalized clinical and preventive intervention approaches. Our findings thus far have implications for the clinical strategy of the treatment of stress-related disorder. Together with our partners we intent to focus among others on the rational use of antidepressant and on early recognition of patients with chronic trajectories who could benefit from specific personalized rehabilitation or treatment approaches. Another line of exploration is the potential of dietary intervention in the containment of aggression. Finally, we do intent to broaden our focus to clinical patients. Together with the department of Adolescent and Child Psychiatry we intent to increase our effort in  population mental health approaches in the LUMC Campus in The Hague. As part of the activities in the AW SAMEN, collaboration is expanded with the department of PHEG on community based health care (H2020 fund submitted) and on the use of clinical data for personalised care (big data project with TNO). As part of the AW, projects directed at goals that are important for communities are being conducted; for example on triage of child mental health disorders in first line services (youth teams and general practicioners). 

Our research approaches match well with Dutch National Research Agenda and the Dutch National research agenda for Mental Health (GGZ) and  the Dutch National Research Agenda (Personalized Medicine, NeurolabNL).

Cohesion within LUMC

LUMC Medical Research profile:  Translational Neuroscience, Innovation in Health strategy and Quality of Care, Aging, Biomedical Imaging

The Department of Psychiatry fosters close collaborations with a multitude of other departments in the LUMC-community, including Child and Adolescent Psychiatry, Endocrinology, Radiology, Public Health and Primary Care, Geriatrics, Neurology, the Centre for Human Drug Research, Medical Decision Making and Clinical Epidemiology. The department collaborates actively, both in profile areas of LUMC and of Leiden University, together with research groups in the Faculty of Social Science.