James Li, PhD – Slide of the Week

James Li Slide of the Week 2019

Title: Validating Psychosocial Pathways of Risk Between Neuroticism and Late Life Depression Using a Polygenic Score Approach

Legend: The prospective association between genetic liability to high neuroticism and late life depression symptoms is partially mediated through the effects of dependent stressful life events at age 53 (shown in the figure above) and social support at age 64 (shown in the figure below). Not shown – associations above were completely replicated using self-reported neuroticism scores, providing a robust validation of psychosocial mechanisms underlying late life depression.

Citation: Li, J. J., Hilton, E. C., Lu, Q., Hong, J., Greenberg, J. S., & Mailick, M. R. (2019). Validating psychosocial pathways of risk between neuroticism and late life depression using a polygenic score approach. Journal of Abnormal Psychology. doi: http://dx.doi.org/10.1037/abn0000419

Abstract: Neuroticism is a stable and heritable personality trait that is strongly linked to depression. Yet, little is known about its association with late life depression, as well as how neuroticism eventuates into depression. This study used data from the Wisconsin Longitudinal Study (WLS; N=4,877) to examine the direct and indirect effects of neuroticism on late life depression at three points in the life course–ages 53, 64, and 71–via stressful life events (i.e., independent and dependent) and social supports measured across adulthood and into later life. Neuroticism was assayed using multiple methods, including self-report measures (phenotypic model) and a polygenic score (polygenic model) informed by a meta-analytic genome-wide association study. Results indicated that the phenotypic model of neuroticism and late life depression was partially mediated via dependent stressful life events experienced after the age of 53 and by age 64 social support. This association was replicated in the polygenic model of neuroticism, providing key evidence that the findings are robust. No indirect effects emerged with respect to age 53 social support, age 71 social support, adult dependent stressful life events (experienced between age 19 and 52), and adult and late life independent stressful life events in either the phenotypic or polygenic models as they pertained to late life depression. Results are consistent with previous findings that individuals with high neuroticism may be vulnerable to late life depression through psychosocial risk factors that are, in part, attributable to their own personality.

About the Lab: James Li’s lab (the Social and Behavioral Development Lab) investigates genetic and environmental factors that contribute to the development of child externalizing disorders (e.g., attention-deficit/hyperactivity disorder, oppositional defiant disorder, and conduct disorder). Research in the lab utilizes molecular genetic approaches (e.g., genome-wide association scans, gene-pathway analysis) to advance understanding about the genetic architecture underlying complex developmental phenomena. They also focus on rigorous measurements of early environmental influences as they relate to child behavioral problems, not only for risk factors such as negative parenting and maltreatment, but also for enriched factors such as positive parenting and social support. The goal of this research is to understand how genes and environments independently and interactively influence variation in child social and behavioral development, and to ultimately bridge the substantial gap between genetics/neuroscience and prevention/intervention.

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