Cristin-resultat-ID: 2054908
Sist endret: 23. september 2022, 14:57
Resultat
Vitenskapelig foredrag
2022

The genomics of psychiatric symptom differentiation in early life

Bidragsytere:
  • Adrian Dahl Askelund
  • Laura Hegemann
  • Elizabeth Claire Corfield
  • Helga Ask
  • Eivind Ystrøm
  • Alexandra Havdahl
  • mfl.

Presentasjon

Navn på arrangementet: World Congress of Psychiatric Genetics
Sted: Florence
Dato fra: 13. september 2022
Dato til: 17. september 2022

Arrangør:

Arrangørnavn: International Society of Psychiatric Genetics

Om resultatet

Vitenskapelig foredrag
Publiseringsår: 2022

Beskrivelse Beskrivelse

Tittel

The genomics of psychiatric symptom differentiation in early life

Sammendrag

Background: An emerging body of evidence suggests that genetic risk for psychiatric conditions is diffuse, probabilistic in nature, and overlaps substantially across different domains. However, psychiatric conditions are diagnosed and treated as specific disorders based on differentiated symptom clusters. In the context of generalised genetic risk, it remains to be determined how distinct psychiatric conditions emerge. The prospects of using genomic data to predict individual-level risk for psychiatric conditions are at present unclear. For prediction to be useful, it needs to be both sensitive (identifying who is at risk) and specific (at risk for what). While increasing sample sizes for genetic discovery may boost sensitivity, the generalised nature of genetic risk implies that identifying predictors of differentiation of psychiatric symptoms may be needed to increase specificity. The Norwegian Mother, Father, and Child Cohort Study (MoBa) is a large population-based pregnancy cohort with genotype and phenotype data, ideally suited to address these questions. Methods: We used the Child Behavior Checklist to assess behavioural and emotional difficulties at ages 1.5, 3, and 5. Symptom¬ differentiation was operationalised as the relative level of these domains over time (behavioural difficulties – emotional difficulties = differentiation). This means that individuals with high scores have relatively more behavioural than emotional difficulties, and the inverse for low scores. These scores can be compared to overall difficulties (behavioural + emotional = total). Following a preregistered analysis plan, we estimated latent growth trajectories of differentiation across early childhood, as well as mediation effects of differentiation on symptoms of psychiatric conditions at age 8. We tested associations between 10 polygenic scores (PGS) for core neurodevelopmental and psychiatric conditions and the extent (intercept) and rate (slope) of the differentiation process. The analytic sample comprised 57,387 genotyped children (including 12,347 pairs of full siblings) from MoBa. We used multilevel structural equation models to account for unmeasured familial confounding, and corrected for multiple comparisons using FDR. Results: ADHD PGS predicted the extent and rate of differentiation toward behavioural difficulties in early childhood (βintercept = 0.10 [0.09, 0.11]; βslope = 0.02 [0.02, 0.03]), and the extent of differentiation at age 5 in turn mediated 33-37% of the PGS associations with ADHD symptoms at age 8. The ADHD PGS association was smaller for total difficulties (βintercept = 0.05 [0.04, 0.06]; βslope = 0.01 [0.01, 0.02]). Schizophrenia PGS predicted differentiation toward emotional difficulties at age 5 (βintercept = -0.03 [-0.04, -0.02]; βslope = -0.01 [-0.02, -0.01]), and bipolar disorder PGS predicted differentiation toward behavioural difficulties (βintercept = 0.02 [0.01, 0.03]; βslope = 0.01 [0.01, 0.02]) – though in both cases effect sizes were substantially smaller. Discussion: We identify genomic predictors of symptom differentiation in early life. Results support a direct effect of ADHD PGS on differentiation toward behavioural difficulties, independent of individuals’ total burden of symptoms. PGS for schizophrenia and bipolar disorder differentially associates with the development of emotional and behavioural difficulties in early childhood. This research may help refine risk predictions in child psychiatry, an important step to enable early prevention.

Bidragsytere

Aktiv cristin-person

Jo Adrian Dahl Askelund

Bidragsyterens navn vises på dette resultatet som Adrian Dahl Askelund
  • Tilknyttet:
    Forfatter
    ved Nic Waals Institutt ved Lovisenberg Diakonale Sykehus

Laura Hegemann

  • Tilknyttet:
    Forfatter
    ved Nic Waals Institutt ved Lovisenberg Diakonale Sykehus

Elizabeth Claire Corfield

  • Tilknyttet:
    Forfatter
    ved Avdeling for psykiske lidelser ved Folkehelseinstituttet
Aktiv cristin-person

Helga Ask

  • Tilknyttet:
    Forfatter
    ved Helse-, utviklings- og personlighetspsyk ved Universitetet i Oslo

Eivind Ystrøm

  • Tilknyttet:
    Forfatter
    ved Helse-, utviklings- og personlighetspsyk ved Universitetet i Oslo
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