Project

Email: natascha.stroo@vu.nl

VU University Amsterdam, Dept. of Biological Psychology

Project Overview

Project Objectives

1. To clarify the role of genetic and environmental factors in the occurrence, course and comorbidity of mental health symptoms across childhood and adolescence.
2. To establish the overlap in genetic risk factors with other characteristics related to childhood mental health symptoms, such as adult mental disorders, IQ and brain structure..
3. To identify genetic (inherited), epigenetic (due to chemical changes to the DNA) and transcriptomic (related to gene expression) variation associated with the occurrence, course and co-morbidity of mental health symptoms during childhood and adolescence.
4. To identify biological pathways associated with mental health symptoms and to validate potential drug targets based on these pathways.
5. To build a prediction model that identifies groups of children that are at highest risk to develop chronic symptoms and that should be targeted for more intensive prevention or treatment programmes.
6. To further develop the already successful EAGLE (EArly Genetics and Lifecourse Epidemiology) consortium into a sustainable international network of researchers in which collaboration is facilitated by data harmonization and IT solutions. This will enable joint analysis of data over cohorts..
7. To build a structure to disseminate the results to a broad audience of scientists, clinicians, patients and their parents and the general public.

These ambitious objectives can be achieved by training of the ESRs in:
- childhood and adolescent mental health symptoms and their (chronic) altereffects (as a result of a non-complete recovery from the mental disorder);
- methods to analyze twin data as well as large-scale (epi)genetic and transcriptomic data across multiple cohorts;
- dissemination of their results also through this website and its blog.

CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe), is a project funded by the European Commission under the HORIZON 2020 Research and Innovation programme, Marie Skłodowska Curie Actions - MSCA-ITN-2016 - Innovative Training Networks.

In the Roadmap for Mental Health and Wellbeing Research in Europe (ROAMER), top-priority is research into child and adolescent mental health symptoms. CAPICE will address this priority.
This network will elaborate on the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, a wellestablished collaboration of the many European birth and adolescent population based (twin and family) cohorts with unique longitudinal information on lifestyle, family environment, health, and emotional and behavioral problems.
Phenotypic and genome-wide genotypic data are available for over 60,000 children, in addition to genome-wide genotypes for over 20,000 mothers and epigenome-wide data for over 6,000 children. Combined with the enormous progress in methodology, the results of the research performed in this network will greatly expand our knowledge regarding the etiology of mental health symptoms in children and adolescents and shed light on possible targets for prevention and intervention, e.g. by drug target validation. Moreover, it will provide Early Stage Researchers (ESRs) with an excellent training in the psychiatric genomics field given by a multidisciplinary team of eminent scientists from the academic and non-academic sector highly experienced in e.g., gene-environment interaction and covariation analyses, (epi)genome-wide association studies, Mendelian Randomization (MR) and polygenic analyses.
With a focus on common and debilitating problems in childhood and adolescence, including depression, anxiety and Attention Deficit Hyperactivity Disorder, CAPICE will contribute to improving later outcomes of young people in European countries with child and adolescent psychopathology.

Work Package 1

Ethics requirements

This work package sets out the 'ethics requirements' that the project must comply with.

Work Package 4

Genetic information as an aid in understanding effects of environmental exposures

By using a combination of Mendelian randomization and epigenetic approaches, including two-step Mendelian randomization of methylation signatures, this WP will identify causal pathways from maternal lifestyle behaviours during pregnancy through to offspring psychological and behavioural problems in childhood, adolescence and early adulthood, including potential epigenetic mechanistic pathways that underlie these causal relationships.

Work Package 7

Training

The training will include courses on the host institution or the co-supervising institution focused on complementary skills such as writing and presenting and on research skills specifically related to their project. In addition, network-wide events will be organized for all ESRs to provide training in the childhood and adolescent psychopathology and state-of-the-art statistical methodology used in large-scale genetic analyses. Finally, to enhance their career perspectives, a workshop on finding a job in academia or industry and an open career day will be organized. The training in dissemination is in close collaboration with WP 5 (see above).

Work Package 2

Data harmonization and genetic epidemiology of childhood mental health symptoms

Through IRT modelling the various phenotypes will be harmonized within cohorts and within age groups. By applying genetic epidemiological methods to twin data, the comorbidity and co-development of mental health symptoms will be studied, with a particular focus on stable genetic factors that are shared across types of problems.

Work Package 5

Database creation and clinical translation

In this WP we will integrate the work of all WPs with the ultimate goal of identifying new drugs for children with behavioral problems. Here we also will work on methods and platforms to share data efficiently without sharing the raw data. A major focus will also be to develop predictions models to identify the children with behavioral problems in need for special attention as well as understand the features that will characterize children with a high likelihood of developing without any major psychiatric or social problems.

Work Package 8

Management

This WP concerns the coordination and overall management of the project and enables the work in all other WPs to run smoothly and coherently, and in line with the implementation section of CAPICE. Communication within the consortium as well as with the European Commission will also be coordinated in this WP.

Work Package 3

(Epi)genetic and transcriptomic factors and the interplay with the environment in childhood mental health symptoms

By genome-wide association analyses and polygenic analytical techniques, this WP will disentangle the role of genetic factors on comorbidity and on the course of common mental health symptoms and identify genetic variants that are associated with common mental health symptoms. Further analyses will reveal how these effects are related to the effects of environmental risk factors and how associations with parental variables can be explained.

Work Package 6

Dissemination

To ensure that the project outputs will be further used and evolved, CAPICE outcomes will be disseminated to a wide set of stakeholders. This will be facilitated by the large network of the partners. Moreover, ESRs are trained in raising awareness campaigns around the project’s activities, showing them the latest innovative and digital instruments used to divulgate science in the information age.