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Estimating direct and indirect genetic effects on emerging variation in depressive symptoms in early adolescence: a trio polygenic score analysis in the MoBa cohort : Author list

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  • Children's MDD polygenic score showed adolescence-specific increase in depressive symptoms (βPGS*wave=0.041, 95% CI 0.017 to 0.065).
  • Developmentally stable direct effects from children's PGS observed for MDD (β=0.016), ADHD (β=0.024) and educational attainment (β=−0.02).
  • Only parental indirect genetic effect was a stable maternal educational attainment PGS effect on child depressive symptoms (β=0.04).
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Eur Child Adolesc Psychiatry. 2026 Oct 6. doi: 10.1007/s00787-026-03197-y. Online ahead of print.

ABSTRACT

Early adolescence is a common period of onset for depressive symptoms. In part, this may reflect a developmental expression of individuals’ genetic propensities as they undergo physiological and hormonal changes and interact with new environments. Many commonly proposed mechanisms assume direct effects of an individual’s own genes on emerging variation in their depressive symptomatology. However, estimates of genetic influence based on analyses in unrelated individuals capture not only direct genetic effects but also genetic effects from parents and other biologically related family members. In data from the Norwegian Mother, Father and Child Cohort (MoBa), we used linear mixed models to distinguish developmentally-stable and adolescence-specific direct and parental indirect genetic effects. In within-family models, we examined effects of polygenic scores for major depressive disorder (MDD), ADHD, anxiety disorders, and educational attainment (EA) on depressive symptoms measured at ages 8 and 14. Children’s own MDD polygenic scores showed adolescence-specific effects on depressive symptoms (βPGS*wave=0.041, [95% CI: 0.017, 0.065]). Developmentally-stable direct effects from children’s polygenic scores for MDD (β = 0.016, [0.006, 0.039]), ADHD (β = 0.024, [0.008, 0.041]) and EA (β=-0.02, [ -0.038, -0.002]) were also evident. The only evidence of indirect genetic effects was a stable effect of maternal EA polygenic scores (β = 0.04, [0.024, 0.054]). Direct genetic effects linked to genetic liability to MDD accounted for emerging variation in depressive symptoms in adolescence. These results imply that specific etiological mechanisms related to MDD may become particularly relevant for depressive symptoms during early adolescence compared to at earlier ages.

PMID:42836998 | DOI:10.1007/s00787-026-03197-y

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