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

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.

Effective dose 50 method as the minimal clinically important difference: Evidence from depression trials.

OBJECTIVE: Previous research on the minimal clinically important difference (MCID) for depression and anxiety is based on population averages. The present study aimed to identify the MCID across the spectrum of baseline severity. STUDY DESIGN AND SETTINGS: The present analysis used secondary data from 2 randomized controlled trials for depression (n = 1,122) to calibrate the Global Rating of Change with the PHQ-9 and GAD-7. The MCID was defined as a change in scores corresponding to a 50% probability of patients "feeling better", given their baseline severity, referred to as Effective Dose 50 (ED50). RESULTS: MCID estimates depended on baseline severity and ranged from no change for very mild up to 14 points (52%) on the PHQ-9 and up to 10 points (48%) on the GAD-7 for very high severity. The average MCID estimates were 3.7 points (23%) and 3.3 (28%) for the PHQ-9 and GAD-7 respectively. CONCLUSION: The ED50 method generates MCID estimates across the spectrum of baseline severity, offering greater precision but at the cost of greater complexity relative to population average estimates. This has important implications for evaluations of treatments and clinical practice where users can use these results to tailor the MCID to specific populations according to baseline severities.