Christian Rück

Purpose and aims: There is so much comorbidity among psychiatric conditions that one can combine them into a single general psychopathology index. Although general psychopathology predicts adverse outcomes, it remains unknown if it responds to intervention. Therefore, we will estimate the causal effect of psychosocial interventions and psychotropic medications on general psychopathology. Method: We will apply casual inference designs (children-of-siblings design

co-twin control/within-individual design

instrumental variable

and front-door criterion) to data from the Swedish Twin Register and Swedish population registers to estimate the effect of childrearing conditions (year 1), psychotherapy (years 2-3), and psychotropic medication (years 1-5) on general psychopathology (derived from self/parent-reported symptoms and psychiatric diagnoses). The principal investigator will devote 50% of his time to this project, and he is supported by experts in epidemiology, psychotherapy, and psychiatry. Importance: Even though comorbidity is the rule rather than exception in psychiatry, most randomized clinical trials exclude individuals with several disorders. Therefore, there is a lack of knowledge of the effect of treatment on comorbidity. By applying innovative causal inference designs to large observational data, we aim to study the effect of treatment on general psychopathology in the best conceivable way. This could open a new area of research into transdiagnostic treatments.

Exhaustion disorder (ED, utmattningssyndrom) is one of the most common and costly mental disorders in Swedish primary care. However, the validity of ED is debated and there are no evidence-based treatments. The core of ED - fatigue - is common across a range of disorders. Recent advances in international research indicate that fatigue is best understood as a transdiagnostic symptom dimension rather than a diagnosis-specific pathology. This paves the way for new, potentially more effective, approaches to assessment and treatment.The purpose of this project is to increase knowledge of fatigue as a transdiagnostic symptom in primary care patients and to build evidence for a highly accessible transdiagnostic treatment for fatigue. Consecutively recruited primary care patients (N=500) with fatigue will be included in a multicenter randomized controlled trial and receive internet-delivered transdiagnostic cognitive behavioral therapy adjunct to care as usual, or care as usual only. Primary outcome will be change in fatigue severity (pre-post treatment) with controlled follow-ups up to 2 years from baseline. Moderators and mechanisms of treatment effect, and cost-effectiveness, will be analyzed.This project has the potential to build solid evidence for an accessible, cost-effective treatment of fatigue that can be readily implemented in primary care. Results will contribute to development of guidelines for assessment and treatment of fatigue, and better use of healthcare resources.

Research problem and specific questionsObsessive-compulsive disorder (OCD) is a serious anxiety disorder affecting about 2% of the population which is associated with substantial disability across a range of domains, including educational attainment and participation in the labour market. According to data from the Swedish national registers, 44% of individuals with a diagnosis of OCD will be receiving disability pension, be in long-term sickness absence or be long-term unemployed at some point during their employable years. The overarching purpose of this project is to implement and evaluate the efficacy and cost-effectiveness of Individual Placement and Support (IPS), a person-centred return-to-work program, which has an extensive evidence base in other serious mental disorders but has yet to be evaluated in individuals with OCD.Data and methodThis will be the first evaluation of IPS for OCD anywhere in the world. We propose to partner with service users, interest organisations, clinicians, employment specialists, and clinic managers to first pilot IPS in specialist OCD services (n=20

AIM 1). With lessons learnt from the pilot, we will then optimise the delivery of IPS in this clinical context and conduct a fully powered randomised controlled trial of IPS plus standard specialist OCD treatment, compared standard specialist OCD treatment alone (N=110

AIM 2). Finally, we will evaluate the cost-effectiveness of the intervention from a societal perspective, including a 2-year follow-up in the registers (AIM 3). Societal relevance and utilisationThis proposal originated as a direct response to a demand from service users who struggle to get on with their lives, even after having received a good treatment for their OCD . Many service users wish to return to work but are unable to. If successful, this project could represent a new model for the reintegration of individuals with OCD in the labour market, which will not only contribute to the holistic recovery of the individual, but also have clear socioeconomic benefits for society.Plan for project realisationThe project brings together a multidisciplinary team of researchers with a track record in OCD research, clinical trials, return-to-work interventions, biostatistics, health economics, and implementation science. The team also includes service users and interest organizations that will contribute with their lived experience, as well as health professionals.

Research problem and specific questionsExhaustion disorder (ED, utmattningssyndrom) is one of the most common and costly mental disorders in Sweden, but the validity of ED is debated and there are no evidence-based treatments. The core of ED - fatigue - is common across a range of disorders, associated with work-disability and excess mortality. There is mounting evidence from international research supporting that fatigue should be conceptualized as a transdiagnostic symptom dimension rather than a diagnosis-specific pathology. Cognitive behavioral therapy (CBT) is effective in reducing fatigue across a range of medical conditions by the same change mechanisms. This speaks for a transdiagnostic treatment approach. The purpose of this project is to increase knowledge of fatigue as a transdiagnostic symptom in primary care patients and to evaluate the effect of a highly accessible transdiagnostic CBT for fatigue on symptom reduction and long-term work disability. We also aim to investigate moderators and mediators of treatment effect and treatment cost-effectiveness.Data and method Consecutively recruited primary care patients (N=500) with fatigue (independent of primary diagnosis) will be included in a multicenter randomized clinical trial and receive internet-delivered transdiagnostic CBT adjunct to care as usual, or care as usual only. Primary outcome will be change in fatigue severity (pre-post treatment). Secondary outcomes include self-rated symptoms, functional ability, and objective measures of cognitive impairment. Registry data will be used for analysis of healthcare consumption and sickness absence to the 1-year follow-up. Societal relevance and utilization  Fatigue is associated with suffering, work-disability, and high societal costs. This project can build solid evidence for an accessible, cost-effective treatment for fatigue with the potential to improve functional ability and prevent long-term sickness absence. Results can contribute to development of guidelines for assessment and treatment of fatigue, evidence-based recommendations for sick-leave prescription, and more efficient use of healthcare resources.Plan for project realization:Patients will be recruited from at least 3 primary care centers in Stockholm, using existing infrasturctures for care. The project group is a multidisciplinary team of researchers and clinicians from Karolinska Institutet, Stockholm University, and Amsterdam University Medical Center, Netherlands.

Background: Cardiovascular diseases (CVD) are responsible for almost one third of the deaths worldwide. Individuals with mental disorders have shown to be a group particularly vulnerable to suffer from CVD. For example, using data from the Swedish registers, our team has established that individuals with obsessive-compulsive disorder (OCD), an impairing disorder affecting about 2% of the population, have an increased risk of obesity, type 2 diabetes, circulatory system diseases, and specific CVDs, with the subtypes venous thrombo-embolism and heart failure being the most relevant. We have also established that these risks in OCD are likely to be a consequence of the disorder itself, rather than attributable to familial factors or medication. Given this, it is crucial to consider lifestyle habits (e.g., physical activity, diet) which may be responsible for the observed CVD risks and are known to be amenable to modification. Objectives: This project is a collaboration between Karolinska Institutet, the Department of Cardiology at Karolinska Universitetssjukhuset, and the specialist OCD and related disorders clinic at Psykiatri Sydväst, Region Stockholm. With the help and support of the Swedish OCD association (Svenska OCD-förbundet), we have developed a lifestyle intervention to reduce metabolic and cardiovascular risk factors in individuals with OCD, which we aim to evaluate in this project. Workplan: We will follow a two-step approach. First, we will conduct a pilot study to test whether our lifestyle intervention, including physical exercise, modification of dietary habits, and other behavioural changes is feasible, safe, and acceptable for the participants. Second, we will conduct a fully powered randomized controlled trial to establish the efficacy of this intervention, compared to medical advice and treatment as usual. We will also evaluate whether this intervention is cost-effective from a societal perspective. Meaning: Our results have the potential to prevent and reduce the cardiometabolic outcomes observed in individuals with OCD. If the lifestyle intervention program proves to be successful in reducing this risk and does so in a cost-effective manner, we will aim to implement the intervention in routine clinical care. Additionally, the intervention could be expanded to individuals with other common mental disorders, such as anxiety and depression, as well as other groups at risk.

Obsessive-compulsive disorder (OCD) is a prevalent and impairing mental disorder associated with an increased risk of metabolic and cardiovascular diseases (CVD) and death due to cardiovascular causes. However, the mechanisms underlying this association are unknown. Moreover, it is unknown if lifestyle modification interventions can reduce cardiometabolic risk factors in individuals with OCD. The objectives of this research project are two-fold. First, we will investigate the causal associations between OCD and CVD using genetic correlations and bi-directional Mendelian randomization. Second, we will evaluate a lifestyle intervention to reduce cardiometabolic risk factors in individuals with OCD. We will do this in two steps. Step 1 is a pilot study to evaluate trial procedures and test the feasibility of the intervention. Step 2 will consist of a randomized controlled trial examining efficacy and cost-effectiveness of the lifestyle intervention for OCD, compared to medical advice and treatment as usual. The results of this project will inform prevention and intervention strategies and clinical guidelines. Additionally, if our lifestyle intervention program proves to be successful in reducing cardiometabolic risk and does so in a cost-effective manner, we will aim to implement the intervention in routine clinical care, which would contribute to reducing morbidity and mortality rates in this population.