The COVID-19 pandemic presented a significant environmental stressor, exacerbating pre-existing vulnerabilities and impacting older adults' mental health. This population faced increased social isolation and vulnerability to severe illness, leading to higher rates of depression, anxiety, and loneliness. Adverse childhood experiences (ACEs) are consistently linked to poorer mental health outcomes in later life, and the pandemic may have accentuated these effects. The long-term impact of ACEs may be explained by dysregulated inflammation and HPA-axis activity. Impairments in these systems are associated with heightened stress reactivity and exaggerated responses to new stressors. Dysregulated cortisol and inflammation levels are associated with poorer mental health outcomes, suggesting a biological pathway from ACEs to psychopathology. While research on the interplay of ACEs, HPA-axis function, and inflammation has yielded mixed results, hair cortisol offers a reliable measure of longer-term cortisol exposure. Genetic factors also play a role in psychological distress, with polygenic scores (PGS) reflecting inherited susceptibility to mental health disorders. The interplay between ACEs and PGS may increase the risk of depression and inflammation. Investigating these factors in older adults is crucial, considering age-related increases in cortisol levels, inflammation, cognitive decline risk, and reduced social connections. This study aimed to investigate whether ACEs, hair cortisol, CRP, and PGS are independent risk factors for psychological distress in older adults during the COVID-19 pandemic and examined interactions among these factors.

Existing literature establishes a strong link between adverse childhood experiences (ACEs) and poorer mental health outcomes, particularly in later life. Research indicates biological and genetic pathways connecting early adversity to psychopathology, involving dysregulated inflammation and altered hypothalamic-pituitary-adrenal (HPA) axis activity. However, the precise relationship between ACEs and HPA-axis function and inflammation remains unclear, with inconsistencies possibly attributed to limitations in cortisol measurement methods. Hair cortisol, as a measure of long-term cortisol exposure, provides a more nuanced perspective. Studies have shown mixed results regarding the relationship between hair cortisol and ACEs. While a consistent association exists between ACEs and elevated inflammatory markers in adults, findings are less consistent in children. The type and timing of adversity seem critical in understanding this relationship. Genetic factors also influence psychological distress, and polygenic scores (PGS) offer a method for assessing the complex genetic basis of psychiatric disorders. Research demonstrates associations between specific PGS and psychological distress, as well as interactions between ACEs and PGS, which accentuate the negative impact of ACEs.

Data from the English Longitudinal Study of Ageing (ELSA), a prospective cohort study of older adults in England, were used. Retrospective ACE information was collected in 2006/7, while CRP and hair cortisol were measured in 2012/13. Psychological distress was assessed before the pandemic (2018-19) and at two COVID-19 assessments in 2020. The analysis included 2050 participants. Outcomes included depression (CESD-8), anxiety (GAD-7 and ONS anxiety scale), and loneliness (UCLA Loneliness scale). Exposures were ACEs (cumulative risk score categorized into 0, 1, and ≥2 ACEs), CRP (binary: ≥3 mg/l), hair cortisol (log-transformed), and PGS for major depressive disorder, anxiety, and loneliness. Covariates included sociodemographic factors, medication use, childhood socioeconomic factors, hair characteristics, and genetic population stratification. Linear/logistic regression models were used for individual associations, and mutually adjusted models were used for examining combined effects and interactions. Mixed-effect models assessed changes in psychological distress before and during the pandemic. Sensitivity analyses explored the impact of lifestyle factors, limiting long-standing illnesses, COVID-19-related worries, and different ACE dimension categorizations.

ACEs were positively associated with all psychological distress outcomes during the pandemic. Having 1 or 2+ ACEs increased the odds of depression and anxiety. ACEs were also positively related to loneliness scores. Hair cortisol was associated with an increased risk of depression, and high CRP was associated with greater loneliness. The relationship between cortisol and psychological distress was larger among participants with ACEs. Individuals with high CRP experienced greater increases in loneliness from before to during the pandemic compared to those with lower CRP levels. Individuals with 2+ ACEs experienced greater increases in depressive symptoms compared to those with none. Higher hair cortisol was also related to worse changes in depressive symptoms across time points. In mutually adjusted models, ACEs and hair cortisol remained associated with depression, and ACEs and CRP remained associated with loneliness. Interaction effects between ACEs and hair cortisol were observed for all psychological distress outcomes. Mixed-effect models showed that individuals with high CRP experienced worse changes in loneliness, and those with 2+ ACEs experienced worse changes in depression. Higher hair cortisol was associated with worse changes in depression. PGS were not significantly associated with outcomes during the pandemic but were associated with pre-pandemic mental health in sensitivity analyses.

The findings support the hypothesis that ACEs, higher cortisol and inflammation, and higher PGS would be associated with greater psychological distress during the pandemic. ACEs were consistently associated with all outcomes, suggesting the pandemic exacerbated their psychological impact. The association between hair cortisol and depression, along with the interaction effect with ACEs, suggests HPA-axis dysregulation may be a key mechanism. The relationship between CRP and loneliness, and the interaction effect with ACEs, implies a role for inflammation in pandemic-related distress. The lack of association between PGS and pandemic outcomes suggests that genetic predisposition may be less influential in responses to acute stressors. However, it's important to note that PGS effects are typically characterized by small effect sizes. The study highlights the importance of considering biosocial vulnerabilities when understanding mental health responses to environmental stressors.

This study demonstrates the lasting impact of ACEs and the interplay of biological factors (cortisol, inflammation) on older adults' mental health during the COVID-19 pandemic. The results underline the need for interventions targeting both the psychosocial consequences of ACEs and biological pathways involved in stress responses. Further research is needed to explore the nuances of these biological pathways and investigate other relevant factors like specific types of ACEs, inflammatory markers, and different cortisol measurement methods. The study also emphasizes the importance of examining the dynamic interplay between genetic predispositions and environmental stressors across different life stages.

Limitations include the sample's lack of ethnic diversity and the use of self-reported data, which may introduce biases. The time lag between exposure measurements and pandemic assessments also affects interpretation. Sensitivity analyses revealed discrepancies suggesting that the way variables are handled can influence observed associations. Differences in demographic characteristics between the analytical sample and excluded participants raise concerns about selection bias and generalizability.