Genetic liability for schizophrenia and childhood psychopathology in the general population

Laurie J Hannigan*, Ragna Bugge Askeland, Helga Ask, Martin Tesli, Elizabeth Corfield, Ziada N L Ayorech, Øyvind Helgeland, Per Magnus, Pål R Njølstad, Anne Siri Øyen, Camilla Stoltenberg, Ole A Andreassen, George Davey Smith, Ted Reichborn-Kjennerud, Karoline Alexandra Havdahl

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

Genetic liability for schizophrenia is associated with psychopathology in early life. It is not clear if these associations are time dependent during childhood, nor if they are specific across different forms of psychopathology. Using genotype and questionnaire data on children (N = 15 105) from the Norwegian Mother, Father and Child Cohort Study, we used schizophrenia polygenic risk scores to test developmental stability in associations with measures of emotional and behavioral problems between 18 months and 5 years, and domain specificity in associations with symptoms of depression, anxiety, conduct problems, oppositionality, inattention, and hyperactivity at 8 years. We then sought to identify symptom profiles—across development and domains—associated with schizophrenia polygenic liability. We found evidence for developmental stability in associations between schizophrenia polygenic risk scores and emotional and behavioral problems, with the latter being mediated specifically via the rate of change in symptoms (β slope = 0.032; 95% CI: 0.007–0.057). At age 8, associations were better explained by a model of symptom-specific polygenic effects rather than effects mediated via a general psychopathology factor or by domain-specific factors. Overall, individuals with higher schizophrenia polygenic risk scores were more likely (OR = 1.310 [95% CIs: 1.122–1.528]) to have a profile of increasing behavioral and emotional symptoms in early childhood, followed by elevated symptoms of conduct disorder, oppositionality, hyperactivity, and inattention by age 8. Schizophrenia-associated alleles are linked to specific patterns of early-life psychopathology. The associations are small, but findings of this nature can help us better understand the developmental emergence of schizophrenia.
Original languageEnglish
Article numbersbaa193
Number of pages11
JournalSchizophrenia Bulletin
Early online date9 Feb 2021
DOIs
Publication statusPublished - 9 Feb 2021

Keywords

  • schizophrenia
  • genetic risk
  • polygenic scores
  • developmental psychopathology
  • childhood emotional and behavioral problems
  • MoBa

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