The Clinical Psychology Research Program: Stress-regulation, cognition and psychopathology

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1 The Clinical Psychology Research Program: Stress-regulation, cognition and psychopathology The clinical program aims to improve assessment, causal understanding and treatment of a specified number of stress-related mental disorders. It does so by developing and testing theoretical models, and by developing and testing therapeutic interventions derived from behavioral science. The primary methodological approach is experimental. The clinical program investigates how distant, recent and current stressors interact with cognitive processes (e.g., attention, memory, thought, reasoning), behavioral processes (e.g., approach and avoidance), and biological processes (e.g., HPA-axis or monoaminergic functioning). In this way the dynamic and complex interaction of motivated cognition with various non-cognitive factors is investigated. Research into this interaction uncovers an underlying vulnerability for mental disorders. Background During the past decade, the Clinical research program has acquired a strong clinical infrastructure. More facilities have become available to conduct both experimental and longterm clinical research in clinical settings. The program now has a formal collaboration with two large mental health institutes (Psycho-Medical Center Parnassia in The Hague, and Rivierduinen in Leiden). The collaborations with the department of Psychiatry of Leiden University Medical Center and with the VALK foundation are also very important. The VALK foundation is a joint enterprise of Leiden University, KLM and Schiphol Airport. Philip Spinhoven and the president of Leiden University are members of the board of this foundation. The program currently has a stable infrastructure for basic and clinical research, which is generally not easy to acquire for a clinical psychology department: many research groups in the world have to find clinical populations ad hoc in order to answer their research questions. These clinical facilities have also provided a basis for the successful application of research grants. The methodological emphasis is on executing experiments. Firstly, fundamental research seeks to isolate psychological or biological mechanisms or processes that are involved in the causation or maintenance of anxiety, depressive and somatoform disorders. Secondly, clinical outcome studies (in particular, randomized controlled trials) aim to reduce psychopathology through specific and well-controlled psychological (or pharmacological) interventions. Because research methods are dependent on the questions asked, sometimes research is non-experimental or quasi-experimental. Although the emphasis is on behavior and on cognitive processes, some of the most interesting research takes place at the interface of psychological and biological approaches and this multi-disciplinary perspective has become more prominent in the program during the last years.

2 Research Areas The Clinical Research Program has four main content areas. The program focusses on three types of disorder: 1. Anxiety disorders 2. Mood disorders 3. Somatoform disorders and the methodology to study these: 4. The trans-diagnostic approach The three common mental disorders constitute a rather unified research topic. All three are stress-related conditions. In clinical practice, the co-morbidity among these conditions is high, and there are also similarities in known causative and maintaining factors, and in preferred psychological and pharmacological treatments Of course, there are also notable differences Within this focus, the program adopts a transdiagnostic approach. The aim is to understand the complex interplay among cognitive, behavioral and biological processes across these three stress-related disorders. This knowledge may contribute to improved treatments and (secondary) prevention measures of mental disorders. Anxiety disorders Cognitive and neurobiological aspects of trauma-related memory (Van der Does, Elzinga, Moorman, Health anxiety among victims and care providers of the Bijlmermeer aviation disaster (Spinhoven, Verschuur) The prevalence of trauma-related symptoms in refugee minors (Eurelings-Bontekoe, The efficacy of cognitive-behavioral and pharmacological treatments of panic disorder, social anxiety disorder and fear of flying ( The role of repetitive behaviors in Gilles de la Tourette and obsessive-compulsive disorder ( The role of attentional bias in panic disorder (Van der Does, Kroeze) Publications within this area can be found here The following PhD-students completed their thesis: Ismay Kremers (UL), Danielle Cath (UL), Lucas van Gerwen (UL), Bram Bakker (UvA), Desiree Oosterbaan (UvA). The theses of the following PhD students are still in progress: Anne Giezen (UL), Nicole Oei (UL), Marieke Tollenaar (UL), Margot Verschuur (UL), Tammy Bean (Centrum 45). Projects 1,2, 3 and 6 will be continued. In project 1, emphasis will be on the effects of stress on prefrontal functions in posttraumatic stress. Three major projects can be differentiated. The first involves the NWO-funded VENI project of Bernet Elzinga entitled The role of prefrontal inhibition on conditioned fear The major aims of this study are to investigate the role of the medial prefrontal cortex in the inhibition of conditioned fear and the role of the stress-hormone cortisol on prefrontal inhibitory dysfunctions. The second project is entitled The role of stress hormones in the extinction of conditioned fear. The third project is the NWO-funded study entitled Accessibility of emotional memories, investigating the role of stress hormones on the retrieval of recent and remote (autobiographical) memories.

3 Clinical research Our new program member Anold van Emmerik has previously demonstrated that structured writing therapy is effective in preventing chronic PTSD and in the treatment of chronic PTSD. With the aid of the program Linguistic Inquiry and Word Count (LIWC) memory for trauma and emotional processing of trauma will be investigated and further experimental and clinical studies in emotional processing during writing about trauma will be pursued. In collaboration with the University of Amsterdam (department of clinical psychology) and Delft University of Technology (department of mediamatics) research into the effectiveness and mechanisms of change in virtual reality exposure therapy for fear of flying will be continued, after having obtained promising results in a pilot study. Mood disorders Cognitive and neurobiological aspects of vulnerability for depression (Van der Does) The effectiveness of cognitive-behavioral treatment of deliberate self-harm (Arensman, Garnefski, Cognitive-behavioral treatment in the prevention of depression (Engels, Hoencamp, The effectiveness of interpersonal therapy in depressed outpatients (Hoencamp,. The effectiveness of outreach consultation, diagnostic assessment and short-term treatment of emotional disorders (especially depression) in general practice compared to care as usual (Hoencamp) The role of negative life events in depression (Garnefski, Kraaij) Determinants and correlates of suicidal behavior (Arensman, Garnefski, de Wilde) Determinants and correlates of homesickness (Eurelings-Bontekoe, Verschuur) Bereavement and depression (Cleiren) The following PhD-students completed their thesis: Vivian Kraaij (UL); The theses of the following PhD students are still in progress: Linda Booij (UL), Nadja Slee (UL), Sachlan Apil (UL), Rimke Haringsma (UL), Wendelien Merens (UL), Ingeborg Pieper (Rivierduinen), Kosse Jonker (Parnassia), Marc Blom (Parnassia), Mirjam van Orden (Parnassia), Claudi Bockting (UvA), Michael Boogaard (GGZ Rotterdam). The research theme of vulnerability to depression of Willem van der Does (project 1) will be intensified. The overall aim is to investigate whether psychological and biological vulnerability profiles can be found, and if treatments can be tailored on the basis of these profiles. The cognitive project, in collaboration with Oxford University, involves measurement and modification of cognitive vulnerability to depression, using mood induction and other experimental paradigms. The biological project, in collaboration with Maastricht, Oxford and McGill, involves investigating cognitive and symptomatic effects of manipulations of monoamine function (e.g. tryptophan depletion, alphalactalbumin or MDMA). The next phases of this research will be: to investigate cognitive and symptomatic effects of short-term manipulations of other neurotransmitters (noradrenaline, dopamine); to investigate the effects of treatments (medications, psychotherapy) on biological and cognitive vulnerability markers; and to investigate brain mechanisms involved in cognitive dysfunctions in depression, using functional neuroimaging. Clinical research The subprogram participates in the Netherlands Study of Depression and Anxiety (NESDA), together with the Department of Psychiatry and the Department of General Practice and

4 Nursing Home Medicine of Leiden University Medical Center. This is a ZonMw-funded largescale longitudinal research project of psychiatrists, general practitioners and psychologists from VU University, University of Groningen, and peripheral research groups (Nivel, Trimbos- Institute, WOK) and several mental health institutions in The Netherlands. Philip Spinhoven is member of the Board of the NESDA consortium. Within NESDA epidemiological, psychological and biological data will be collected in patients during the next 10-years. Moreover, the prevention of depression in elderly subjects will be investigated using a stepped-care framework (Zon-MW-funded, in collaboration with Parnassia, Trimbos-Institute, VU University (Departments of Psychiatry and General Practice) and University of Groningen (Departments of Psychiatry, Internal Medicine and Geriatrics)). Finally, a collaborative research project with Rivierduinen and Parnassia in a ZonMw-funded project on the prevention of recurrent deliberate self-harm in younger adults will be continued. In these studies the clinical relevance of cognitive vulnerability for depression will be explicitly addressed. Somatoform disorders The efficacy of cognitive-behavioral and pharmacological treatment of unexplained chest pain (Van der Does, The efficacy of cognitive-behavioral and pharmacological treatment of hypochondriasis (Van der Does, The efficacy of self-hypnosis in the treatment of conversion disorder (Roelofs, The role of control in pain perception (Janssen, The role of trauma and dissociation in medically unexplained somatic symptoms (Roelofs, Information processing in conversion disorder (Roelofs) Epidemiology and treatment of somatoform disorders in general practice ( A population-based study of chronic daily headache (CDH) and abuse of headache drugs ( The following PhD-students completed their thesis: Anke van Peski-Oosterbaan (UL), Franny Moene (APZ De Grote Rivieren), Ellert Nijenhuis (APZ Drenthe), Jarl Kuyk (SEIN). The theses of the following PhD students are still in progress: Eduard van Dijk (UL), Anja Greeven (UL), Jacobien Peer (UL), Ingrid Arnold (LUMC), Margot de Waal (LUMC), Patricia Bakvis (SEIN), Miranda Swinkels (SEIN). A new research project involves the role of stress and prefrontal functions in somatoform disorders. Three major projects can be differentiated. The first involves the NWO funded VENI project of Karin Roelofs entitled Stress and Prefrontal Motor Control in Conversion Paralysis It is a study in which neuroimaging (fmri) and neuroendocrinological (cortisol) measures are applied to study freezing, approach and avoidance reactions in patients with conversion paralysis. The second project is entitled: The Neurological Underpinnings of Approach and Avoidance Behavior, an ERP study on the influence of endogenous cortisol and trait avoidance on electrophysiological markers of approach-avoidance behavior. The third project is entitled Stress and Prefrontal Functioning in Patients with Psychogenic Pseudo-Epileptic Attacks (PPEAs) (funded by a Teding van Berkhout Fellowship), investigating several markers of the HPA-axis and its relation to the failing integrative prefrontal functions in patients with PPEAs.

5 Clinical research In collaboration with the Department of General Practice and Nursing Home Medicine and the Department of Psychiatry of Leiden University Medical Center a research project investigating the effectiveness of an integrated cognitive-behavioral treatment for major depressive disorder with co-morbid pain or fatigue will be conducted. A systematic collaboration of the general practitioner with community psychiatric nurses will be part of the treatment protocol. This proposed study now under review by ZonMw is part of the ZonMw Netherlands Study on Depression and Anxiety (NESDA), a multicenter longitudinal study on the prognosis of depression and anxiety (see above). Transdiagnostic issues During the last seven years some additional research was directed at improv ing description, classification and assessment of phenomena relevant for the under standing and treatment of the spectrum f anxiety, mood and somatoform disorders. For executing the studies mentioned above it is important to develop and test various diagnostic, process and evaluation instruments: The assessment of personality disorders, traits and profiles (Duijsens, Eurelings- Bontekoe, Moorman) The assessment of the use of cognitive emotion regulation strategies to cope with the sequelae of stress (Garnefski, Kraaij) Anxiety, depressive and somatoform disorders show a high overlap with dysfunctional personality traits and disorders. These personality problems may be related to vulnerability for the development and maintenance of these disorders. Liesbeth Eurelings-Bontekoe will continue her research activities into the assessment of personality traits and profiles with special emphasis on anxiety, depressive and somatic complaints. Besides a further validation of a profile interpretation of dimensional assessments of personality, the predictive value of personality problems and disorders for treatment outcome in somatoform disorders (e.g. chronic RSI and pelvic pain) will be studied. After developing a valid and reliable new questionnaire (the Cognitive Emotion Regulation Questionnaire (CERQ)), to measure cognitive emotion regulation strategies after the experience of negative life stress or trauma, results of studies in various clinical, at risk and general population samples have shown that cognitive emotion regulation strategies play an important role in the relationship between the experience of negative life stress or trauma and the reporting of symptoms of psychopathology. In order to extend these findings new research projects of Nadia Garnefski will focus on the moderating role of cognitive emotion regulation strategies in specific samples (traumatized people, people with chronic illness, adolescents, adults, elderly, clinical populations, general populations), with various research methods (written questionnaires, interviews, experimental studies), and in longitudinal designs. By linking research traditions of trauma processing, emotion regulation and models of stress-coping, this line of research is on the interface of the two subprograms of the division of Clinical and Health Psychology.

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