Childhood trajectories of internalising and externalising problems associated with a polygenic risk score for neuroticism in a UK birth cohort study

Ilaria Costantini*, Hannah M Sallis, Kate M Tilling, Daniel Major-Smith, Rebecca M Pearson, Daphne-Zacharenia Kounali

*Corresponding author for this work

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

Abstract

Key points

Neuroticism is an important risk factor for mental health problems with a moderate heritable component; however, it is unclear how genetic liability to neuroticism associates with severity and persistence of emotional and behavioural problems across childhood.

The present study used a prospective design to examine the association between a polygenic risk score for neuroticism and a host of psychological outcomes in addition to its association with trajectories of emotional and behavioural problems in over 6000 children.

We found that the PRS associated with a more difficult temperament, more emotional and behavioural problems, and greater risk of being diagnosed with a clinical disorder in childhood. The PRS was also associated with higher levels of emotional and behavioural problems trajectories and dampened recovery from emotional problems across childhood.

Our study illustrates the importance of genetic in the severity and persistence of emotional problems across childhood. Trio analyses may elucidate the causal relationship between genetic liability to neuroticism and child psychiatric outcomes.



Abstract

Background
Neuroticism represents a personality disposition towards experiencing negative emotions more frequently and intensely. Longitudinal studies suggest that neuroticism increases risk of several psychological problems. Improved understanding of how this trait manifests in early life could help inform preventative strategies in those liable to neuroticism.

Methods
This study explored how a polygenic risk score for neuroticism (NEU PRS) is expressed from infancy to late childhood across various psychological outcomes using multivariable linear and ordinal regression models. In addition, we employed a three-level mixed-effect model to characterise child internalising and externalising trajectories and estimate how a child PRS associated with both their overall levels and rates of change in 5279 children aged 3–11 in the Avon Longitudinal Study of Parents and Children cohort.

Results
We found evidence that the NEU PRS was associated with a more emotionally sensitive temperament in early infancy in addition to higher emotional and behavioural problems and a higher risk of meeting diagnostic criteria for a variety of clinical disorders, particularly anxiety disorders, in childhood. The NEU PRS was associated with overall levels of internalising and externalising trajectories, with a larger magnitude of association on the internalising trajectory. The PRS was also associated with slower rates of reduction of internalising problems across childhood.

Conclusions
Our findings using a large, well-characterised birth cohort study suggest that phenotypic manifestations of a PRS for adult neuroticism can be detected as early as in infancy and that this PRS associates with several mental health problems and differences in emotional trajectories across childhood.
Original languageEnglish
Article numbere12141
Number of pages13
JournalJCPP Advances
Early online date22 Feb 2023
DOIs
Publication statusE-pub ahead of print - 22 Feb 2023

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