Tittel på avhandlingen: The Differentiation of Mental Health Problems in Early Life: Causes and Consequences
Tid og sted: 19. september 2024 kl. 12:15 - 15:00, Auditorium 1, Harald Schjelderups hus.
Prøveforelesning med tittelen: Genes, environment, or both? The state-of-the-art on genetic versus environmental risk and protective factors for mental health problems in children and adolescents, avholdes samme sted kl. 10:15
Askelund er tilknyttet forskningsgruppen The Psychatric Genetic Epidemiology (PaGE) group ved Lovisenberg.
Mer info på UiO sine nettsider.
Populærvitenskapelig sammendrag
Slik påvirker puberteten ungdommers psykiske helse
Hva er årsaken til at noen ungdommer opplever psykiske helseproblemer gjennom puberteten, mens andre klarer seg fint? Og hvorfor er det en sterk økning i forekomst av depresjon blant jenter i ungdomsårene? Ny studie ved Folkehelseinstituttet og Nic Waals Institutt finner svar.
Forskning har vist at de som kommer tidlig i puberteten har økt risiko for psykiske problemer. Nå har en ny norsk studie fulgt over 13,000 jenter gjennom ungdomstiden for å se om tidspunktet for første menstruasjon påvirket deres psykiske helse. De fant at tidligere menstruasjon ga økt risiko for depresjon, men ikke andre psykiske lidelser.
Hva betyr det at første menstruasjon skjer tidlig? Puberteten skjer tidligere i befolkningen nå enn for flere tiår siden. Særlig de som gjennomgår puberteten tidligst ser ut til å være i økt risiko. I et land som Norge innebærer det som oftest at første menstruasjon, som markerer sluttfasen av puberteten og overgangen til ungdomstiden, skjer i 9-11 års alder.
Studien, som ble utført i samarbeid med Universitetet i Oslo, Bristol, og Harvard, er basert på data fra den norske Mor, Far og Barn-undersøkelsen. I denne studien ble alle norske kvinner invitert til å delta dersom de fødte barn ved sykehus i tidsrommet 1999-2008. Nå som disse barna har blitt ungdommer, har forskerne brukt avanserte genetiske metoder for å finne ut om tidlig menstruasjon forårsaker psykiske problemer. De fant at genvarianter som styrer når puberteten skjer også henger sammen med høyere risiko for depresjon, noe som støtter deres årsaksforklaring.
Funnene viste økt forekomst av diagnoser på depresjon hos de med tidlig menstruasjon, men ikke andre psykiske lidelser, som angst eller atferdsforstyrrelser. Det var også tegn til økt forekomst av ADHD-diagnoser, en nevroutviklingsforstyrrelse. Dette er noe foreldre og lærere kan være ekstra oppmerksomme på – selv om de aller fleste som opplevde første menstruasjon tidlig ikke utviklet depresjon.
Scientific Abstract
In this thesis I explore the aetiology of mental health problems, addressing the overall question: how and why do different conditions emerge across development? It has been proposed that different mental health conditions emerge as the result of a process of differentiation, from relatively broad and undifferentiated traits in early childhood to specific symptom clusters later in development. However, only a limited number of previous studies have focused on differentiation. With its rich longitudinal phenotype data, the population-based Norwegian Mother, Father, and Child Cohort Study (MoBa) is ideally suited for investigating this question. This work resulted in three papers, exploring the role of (1) environmental, (2) genetic, and (3) developmental mechanisms of differentiation.
In the first paper, titled “Exploring the differentiation of behavioural and emotional problems across childhood: A prospective longitudinal cohort study”, my co-authors and I developed and validated an approach to studying the differentiation of behavioural and emotional problems across childhood. Using questionnaire and linked healthcare registry data on approximately 79,000 children from MoBa, we identified patterns of differentiation in early childhood that were associated with symptoms and diagnoses of specific behavioural and emotional conditions later in childhood and adolescence. Furthermore, we identified modifiable environmental factors associated with differentiation, some of which remained after accounting for confounding by unobserved familial risk using a subsample of ~24,000 siblings. Notably, maternal at-risk drinking and prenatal distress consistently predicted differentiation in early childhood.
In the second paper, titled “The genetic architecture of differentiating behavioural and emotional problems in early life”, my co-authors and I used the previously validated approach to examine the genetic underpinnings of differentiation between behavioural and emotional problems. Using genomic structural equation modelling in ~56,000 MoBa children, we sought to identify genetic signal in this developmental process and examine its correlations with liability to 11 mental health and neurodevelopmental conditions. We uncovered genomic signal in differentiation, which was primarily related to common variants associated with neurodevelopmental conditions. In polygenic score analyses, liability to attention-deficit hyperactivity disorder (ADHD) was most strongly associated with differentiation toward behavioural problems. Furthermore, using polygenic scores from ~33,000 parent-offspring trios, we found that genetic effects were primarily direct rather than indirect.
In the third paper, a Registered Report titled “Assessing causal links between age at menarche and adolescent mental health: a Mendelian randomisation study”, my co-authors and I assessed the role of pubertal timing in the emergence of various mental health issues in adolescence. Using the onset of menses (menarche) as our measure of pubertal timing in ~13,400 MoBa adolescents, we tested associations between age at menarche and different mental health problems. We triangulated evidence from different causal inference methods to assess whether these associations are likely to reflect causal effects. We found support for the hypothesis that having an earlier age at menarche is associated with elevated risk of adolescent depression, and that this relationship is causal. On the other hand, results did not suggest that effects of age at menarche extend to other domains of mental health.
In the introductory chapters of the thesis, I discuss the shared genetic and environmental underpinnings of different mental health conditions, their co-occurrence and differentiation across development, and associated mechanisms, including the role of pubertal timing in adolescent mental health. This sets the stage for the analyses carried out in each of the three papers. I then summarise the main findings and discuss themes emerging across the three papers, as well as their implications, before addressing important methodological considerations and limitations.
Overall, the first two papers introduce an approach to studying the differentiation of behavioural and emotional problems, identifying specific environmental and genetic mechanisms associated with this process in early childhood. Both papers involve preregistered analyses of prospective longitudinal data, larger in scale than most previous studies. Conducting in-depth genomic discovery of longitudinal phenotypes is a relatively novel approach in the field, and this proves both feasible and informative, highlighting the key role of liability to neurodevelopmental conditions in differentiation. In the final paper, we examine pubertal timing as a mechanism related to different adolescent mental health problems, finding evidence of its causal role in depression specifically. Across all three papers, findings suggest that specific mechanisms contribute to the differentiation of mental health problems across development. Although results for some mechanisms are consistent with a causal interpretation, caution is warranted. Furthermore, since all three papers rely on data from the MoBa cohort, findings should be replicated in other cohorts to test the generalisability of the identified mechanisms.
This research underscores both the shared genetic and environmental factors influencing mental health problems and the critical role of domain-specific mechanisms in early life. These mechanisms may be driven by factors at multiple levels of analysis, ranging from molecular processes to prenatal exposures and social factors. Exploring these nuances may shed light on the interrelated aetiological mechanisms driving the developmental emergence and differentiation of specific mental health conditions.
