To facilitate the organisation and management, CoCA is structured into 11 Work packages (WPs) and each of these WPs has a leader, who supervises and adjusts the process flow and works closely with the project office. Varying numbers of parties are further involved in contributing to the WPs.
Please click on the name of the Work Package for a more detailed description:
WP 01 Research: Epidemiology and Socioeconomic Impact
While all of the disorders studied are common, precise estimates of their comorbid prevalence and their socioeconomic impact are needed. In addition, patterns of comorbidity across the lifespan and their stability across generations are not well documented. Nor have gender effects on impact and persistence been described. WP1 will use very large population samples and datasets from German health insurances (n=8,000,000) to study these issues. WP1 will A) determine medical costs and work loss by performing health-economic analyses and document the pattern of costs stratified by comorbidity type and sex, B) investigate patterns of comorbidity across the lifespan, C) describe sex-specific patterns of comorbidity, and D) document multigenerational transmission patterns of comorbidity.
WP 02 Genetic and Environmental Risk Factors for ADHD and its Comorbidities
WP2 will use well-characterized pre-existing samples to identify genetic and environmental risk factors for the overlap of ADHD, mood/anxiety disorders, SUD, and obesity, and to test whether genetic subgroups with potential prognostic implications can be defined. WP2 also uses all publicly available GWAS data to assess polygenic overlap among the disorders – accompanying work in WP1 –, and to test the role of biological pathways defined by the DA and CIRCA mechanisms. Hypothesis-free approaches using polygenic scores and pathway analysis will discover additional pathways. Using machine-learning, WP2 explores causal relationship between DA, CIRCA and ADHD/comorbidities.
WP 03 Role of Circadian Rhytms in ADHD and its Comorbidities (CIRCA)
This studies the mediating role of the circadian system and sleep in the link between ADHD and its comorbidities. WP3 will use epidemiologic data, which is linked to genotypes to study the mediating role of the circadian system, and will assess the impact of genetic variation therein on brain structural/functional connectivity. WP3 will also study the role of circadian parameters on behavioural, endocrinological, and molecular levels by gene expression studies, hormone measurements and by assessing circadian preference, sleep behaviour and quality using m-Health approaches. WP3 will perform the same non-invasive biorhythm assessments in a sub-set of participants from the clinical trial (WP6) with phenotyping done before and after the intervention to assess suitable biomarkers.
This study will be conducted in Rostock, Germany. To participate please contact the Clinic and Policlinic for Psychiatry and Psychotherapy (UMR).
WP 04 Dopaminergic Neurotransimission and the Reward System (DA)
WP4 focuses on a multi-level analysis of the dopamine mechanism and will analyse epidemiologic studies to test whether reward processing moderates the outcome of ADHD and comorbid disorders. The interplay between genetic/environmental factors, ADHD diagnosis, comorbidity and the dopamine system is studied together with WP1/2 and experimentally validated in healthy volunteers undergoing pharmacoMRI with dopamine agonists/antagonists. A sub-sample of participants of the clinical trial (PROUD; WP6) is studied with these paradigms to probe whether DA is a useful biomarker to stratify patients regarding their risk for comorbidity and therapy response.
This study will be conducted in Frankfurt am Main / Rhine-Main region, Germany and Nijmegen, Netherlands. To participate please contact the Department of Psychiatry, Psychosomatic Medicine and Psychotherapy (GUF-PPP).
WP 05 m-Health Approaches for Monitoring and Coaching Chronobiology and Physical Activity in ADHD and Comorbid Conditions
A m-Health monitoring and feedback system to be used in WP6 is developed using modern smartphone-based systems to 1) cost-effectively, objectively, and reliably measure real-life behaviour; 2) analyse behaviour in real-time and provide encouraging feedback to participants to reinforce functional behaviour. All participants in the trial conducted in WP6 will be monitored by a contracted smartphone with this pre-installed app, monitoring physical activity and circadian pattern. In addition, we will assess physical fitness components that are strong predictors of future obesity and mental diseases.
WP 06 Pilot Randomized-Controlled Phase IIa trial on Prevention of Comorbid Depression and Obesity in ADHD (PROUD)
In WP6, the randomized, single-blinded, controlled PROUD study in 14-30 year old adolescents and young adults with ADHD will be performed. The aim of the study is to prevent the development of major comorbid disorders in ADHD, such as depression and obesity, and to improve general health. Two active interventions are compared to guideline based treatment as usual. One intervention is an exercise-based intervention, the other intervention is bright light therapy. Interventions will be supported by an Health App application developed in WP5. All outpatients with ADHD are invited to participate in the trial. Four study centers take part: Barcelona, Frankfurt, London, and Nijmegen.
WP 07 Research and Piloting: Classification and Prediction
WP7 will generate predictive biomarkers for disease and response to treatments. WP7 will use methods from machine learning and diagnostic accuracy analysis to predict outcomes in datasets from WP1 & 2 using our candidate mechanisms as starting points. WP7 will then use the resulting classifiers in real life patients from WP3 & 6 as a proof of concept. WP7 will also assess the relevance of these classifiers with respect to the specific mechanisms tested in WP3 & 4. WP7 will assess the degree to which results from other WPs have significant degrees of predictive utility which can be useful for health care planning and allocating scarce resources for prevention and treatment.
WP 08 Novel Treatment targets in ADHD and its comorbid conditions
In WP8 Candidate proteins emerging from WP2 & 7 will be subjected to evaluation as potential novel treatment targets for ADHD and comorbid disorders using chemical libraries. Candidate proteins with known high-resolution 3D structures will be screened in silico with subsequent high-throughput in vitro assays. A major goal of WP8 is to produce new leads to “repurpose” existing treatments for ADHD and its comorbid conditions that also will generate hypotheses for future clinical trials.
WP 09 Impact and Dissemination
The impact of our program will be substantial in the fields of prevention and health promotion, clinical/social management of disease, and therapy development. The dissemination of CoCA’s work will be tuned to the corresponding stakeholders, i.e. policy makers, academic and commercial parties interested in therapy development, and public and private health care providers. Importantly, as CoCA will emphasize the role of life-style modifications (sleep, exercise) in preventing and treating ADHD-related comorbidity, the general public and patients themselves are among the most important audience to be targeted also using social media and related approaches. Optimal tuning of dissemination to stakeholders for maximal impact will be achieved through a communication plan.
WP 10 Training and Ethics
Training within CWP10 incorporates three components. First, we will run specialized training courses on project topics; second, we will set up a mentoring programme, which aims to foster the career development of all early career and female researchers. Third, we will provide extensive ongoing training, ensuring standardization of data collection procedures and analyses. Project-wide ethical conduct will be monitored and supported by an internal ethics board. CoCA will comply with all legal regulations and recommendations of the EU, national legislation and local ethics committees.
WP 11 Project Management
The management WP is by led by the coordinator – who is experienced in conducting EU projects – together with concentris, a SME with longstanding, hands-on expertise in the management of EU Framework projects (e.g. Aggressotype, MATRICS, IMAGEMEND, PRISM). Together they take care of the management of contractual, financial, legal, administrative and scientific issues. They ensure the proper functioning of the project in order to achieve the objectives, to complete the Milestones and Deiverables in time and make sure that the consortium’s contractual duties are carried out. In addition, it establishes a communication infrastructure which enables the partners to communicate efficiently and to stay connected for the run-time of the project.
Gain insight into the mechanisms underlying this comorbidity triad with its huge burden for healthcare, economy, and society