Early Life Stress and Genetic Risk for Neuroticism Predicting Health Outcomes in Older Swedish Twins

Introduction: High neuroticism is a predictor of many negative health outcomes and lower well-being in older populations. However, neuroticism itself is likely shaped by gene-environment (GE) interplay already early in life... [ view full abstract ]

Introduction: High neuroticism is a predictor of many negative health outcomes and lower well-being in older populations. However, neuroticism itself is likely shaped by gene-environment (GE) interplay already early in life and thus, these genetic and childhood environmental factors might influence various health outcomes across the life span. To date, the interplay between early life stress and genes underlying neuroticism remain poorly understood. Since neuroticism has a complex genetic architecture, a polygenic risk score approach would help to further improve our understanding of such GE interplay.

Aim: This study explored how early life stress exposure, polygenic risk scores for neuroticism (PRSn) and their interplay influence psychosocial and health outcomes in the second half of the life-span.

Methods: The Swedish Adoption/Twin Study of Aging followed twins reared apart and matched twins reared together over a 30-year time period. The current study uses cross-sectional data from the first measurement occasion, resulting in a total of 1956 individuals. Genotype data were available for a subset of 637 individuals. Rearing status (reared apart or together) is considered an objective indicator of early life stress (median age at separation=2). PRSn were created at seven p-value thresholds. Outcomes included psychosocial factors (socioeconomic status, life stress, family environment) as well as several emotional health (neuroticism, depressive and anxiety symptoms, life satisfaction) and physical health (self-rated health, disease burden, functionality level) measures.

Results: Early stress exposure predicted higher levels of neuroticism, life stress and loneliness, and lower life satisfaction and self-rated health in late-life. PRSn consisting of approximately 10 000 SNPs under p-value threshold of .01 was the most powerful predictor of measured neuroticism late in life. PRSn also predicted high depressive symptoms, loneliness and poor family environment. Interestingly, rearing status and PRSn interacted in predicting depressive symptoms and loneliness, wherein genetic effects were stronger in twins not exposed to early life stress, indicating possible underlying gene-environment interplay. 

Conclusions: These results suggest the importance of early life stress and genetic predisposition to emotional instability in shaping health and well-being in old age.