Same genes, different disorders: understanding the developmental emergence of different psychiatric problems in the context of common genetic liabilities (MoBa-Dev)

Findings from MoBa-Dev submitted for publication and presented at international conference in 2022In 2022, the PhD candidate 1) submitted a manuscript on the differentiation of behavioural and emotional problems in children, 2) presented further analyses on the genomics of differentiation at a conference, and 3) received in-principle acceptance for a Registered Report investigating links between pubertal timing and adolescent mental health.Since the last reporting period, the first analytic project on the differentiation of emotional and behavioural problems in early childhood has been written up, uploaded as a pre-print for early review by the scientific community, and submitted for publication (currently under review). In this project, we have identified several environmental factors associated with differentiation across childhood. That is, as well as demonstrating that some factors are linked to generalised vulnerability to developing emotional and behavioural problems, we have found that others are more associated with a process of differentiation toward either behavioural or emotional problems. Maternal drinking behaviour is one such factor - we found that this was linked to children having relatively more behavioural problems than emotional problems. The candidate has followed up the work in the first project by conducting extensive genomic analyses of psychiatric symptom differentiation in early life. These analyses have been preregistered, and preliminary findings were presented in a talk at the World Congress of Psychiatric Genetics in Florence, Italy in 2022. In this project, genetic liability to developing attention deficit hyperactivity disorder (ADHD) was seen to be an important factor driving the differentiation of symptoms towards behavioural problems. The candidate is currently working on finalising the analyses and writing up the results for publication. Also in 2022, a Registered Report on the impact of pubertal timing on adolescent mental health was awarded acceptance-in-principle in BMC Medicine, based on a thorough review of the Stage 1 protocol. This highly detailed protocol was prepared before data was available to the researchers, protecting against many forms of biases that can affect hypothesis-testing research. Towards the end of 2022, the 14-year data in MoBa became available, enabling the candidate to begin on the analyses and preparing the Stage 2 Registered Report. In this format, the Stage 2 report will be published regardless of what the results look like, provided that the Stage 1 protocol is followed. In this project, the MoBa-Dev team aims to establish whether early onset of menses (as a marker of early pubertal timing) has a causal impact on the development of different mental health problems in adolescents, using advanced statistical and genetic methods. During the reporting period, the candidate has also contributed to 3 additional publications as part of large-scale projects focusing on replication efforts and the Covid-19 pandemic, and to an analytic project now under review and available as a preprint, in which the role of maternal at-risk drinking in early life behavioural and emotional problems was investigated in the context of genetic susceptibility. During the next reporting period, the candidate aims to pre-print and submit the paper on the genomics of psychiatric symptom differentiation and the Stage 2 Registered Report, in addition to preparing the PhD dissertation for submission. Work on the MoBa-Dev project will continue until November 2023.

Preliminary results support the validity of a new approach to study symptom differentiation in childrenIn 2021, the PhD candidate has continued with the statistical analyses for a study of differentiation of mental health problems in children, and developed a Registered Report investigating the causal role of pubertal timing in different adolescent mental health disorders.The first project develops a novel approach to study differentiation of emotional and behavioural problems in early childhood and how this relates to mental health disorders later in childhood and adolescence. Furthermore, the project aims to identify which aspects of the child's early environment contribute to this differentiation, accounting for unobserved familial risk. The analysis plan for the project has been preregistered. Preliminary results validate the approach, and tentatively show that multiple environmental factors predict symptom differentiation in early childhood. The findings from this analysis will be written up, pre-printed, and submitted for publication during the next reporting period. In the second project, the MoBa-Dev team aims to establish whether early onset of menses (as a marker of early pubertal timing) has a causal impact on the development of different mental health problems in adolescents, using advanced statistical and genetic methods. With the help of a broad team of collaborators, the candidate has prepared and submitted a Stage 1 Registered Report on this topic (a highly detailed protocol that is peer reviewed and can be accepted in principle before analyses are done, meaning that the eventual Stage 2 article will be published regardless of results). For this project they plan to use the 14-year MoBa data, which is yet to be released. This approach ensures that analyses are free from biases that can arise when the data is already available, following open science principles. Next, the candidate plans to investigate genetic and environmental moderators of risk and resilience in children whose mothers have symptoms of mental health problems such as anxiety and depression. The candidate has completed all of the compulsory courses in the PhD programme at the Department of Psychology (UiO) in 2021, and started a social network with 100 PhD candidates from the department, organising regular academic and social events. On the side, the candidate has contributed to large-scale research projects related to the Covid-19 pandemic, of which one was published in Nature Human Behaviour and another was accepted in PNAS in 2021. Work on the MoBa-Dev project will continue until November 2023.

Differentiation of mental health problems in children and adolescentsThe main aim of the project is to investigate why young people develop different mental health problems, exploring the impact of genetic and environmental factors.Progress in psychiatric genetics has shown that genetic risk for mental health problems is more generalized than disorder-specific. However, even people with a similar genetic ‘starting point’ go on to develop specific mental health problems such as 'panic disorder' and 'ADHD'. So why, in the context of generalized genetic risk, do specific disorders emerge? Are there environmental exposures that contribute to symptom differentiation throughout an individual’s lifespan? Are the effects of subtle differences in individuals’ genetic risk profiles amplified over time? The MoBa-Dev team will address these questions by applying a unique combination of methods to data from the Norwegian Mother, Father, and Child Cohort Study (MoBa). MoBa is a longitudinal pregnancy cohort study including more than 114,000 children, 90,000 mothers and 70,000 fathers. The ultimate goal of this research is to provide clinicians with information about who is at risk, and for which mental health disorders. Adrian Dahl Askelund, Cand. Psychol., was employed as the PhD candidate of this project on the 1st of November 2020. The project is conducted as part of the Psychiatric Genetic Epidemiology (PaGE) group at Nic Waals Institute within Lovisenberg Diaconal Hospital, in collaboration with the Norwegian Institute of Public Health, the MRC Integrative Epidemiology Unit at the University of Bristol (MRC IEU), King's College London and University College London. The PhD candidate is currently undertaking the statistical analyses for a study of differentiation of mental health problems in children. Next, he plans to investigate the factors and mechanisms behind symptom differentiation and resilience in adolescents, pending the release of the 14-year data. He finally aims to establish the potential causal role of any identified mechanisms using state-of-the-art genetic methods.