TY  - INPR
TI  - The genetic architecture of differentiating behavioral and emotional problems in early life
Y1  - 2025/01/09/
AV  - public
N1  - © The Author(s), 2025. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. https://creativecommons.org/licenses/by/4.0/
ID  - discovery10203221
N2  - Background:
Early in life, behavioral and cognitive traits associated with risk for developing a psychiatric condition are broad and undifferentiated. As children develop, these traits differentiate into characteristic clusters of symptoms and behaviors that ultimately form the basis of diagnostic categories. Understanding this differentiation process ? in the context of genetic risk for psychiatric conditions, which is highly generalized ? can improve early detection and intervention.//

Methods:
We modeled the differentiation of behavioral and emotional problems from age 1.5-5 years (behavioral problems ? emotional problems = differentiation score) in a pre-registered study of ?79,000 children from the population-based Norwegian Mother, Father, and Child Cohort Study. We used genomic structural equation modeling to identify genetic signal in differentiation and total problems, investigating their links with 11 psychiatric and neurodevelopmental conditions. We examined associations of polygenic scores (PGS) with both outcomes and assessed the relative contributions of direct and indirect genetic effects in ?33,000 family trios.//

Results:
Differentiation was primarily genetically correlated with psychiatric conditions via a ?neurodevelopmental? factor. Total problems were primarily associated with the ?neurodevelopmental? factor and ?p?-factor. PGS analyses revealed an association between liability to ADHD and differentiation (?=0.11 [0.10,0.12]), and a weaker association with total problems (?=0.06 [0.04,0.07]). Trio-PGS analyses showed predominantly direct genetic effects on both outcomes.//

Conclusions:
We uncovered genomic signal in the differentiation process, mostly related to common variants associated with neurodevelopmental conditions. Investigating the differentiation of early life behavioral and emotional problems may enhance our understanding of the developmental emergence of different psychiatric and neurodevelopmental conditions.
SN  - 0006-3223
UR  - https://doi.org/10.1016/j.biopsych.2024.12.021
PB  - Elsevier BV
JF  - Biological Psychiatry
KW  - differentiation; behavioral problems; emotional problems; attention-deficit/hyperactivity disorder; genomic structural equation modeling; trio polygenic score.
A1  - Askelund, Adrian Dahl
A1  - Hegemann, Laura
A1  - Allegrini, Andrea G
A1  - Corfield, Elizabeth C
A1  - Ask, Helga
A1  - Davies, Neil M
A1  - Andreassen, Ole A
A1  - Havdahl, Alexandra
A1  - Hannigan, Laurie J
ER  -