TY - JOUR T1 - A longitudinal study shows stress proliferation effects from early childhood adversity and recent stress on risk for depressive symptoms among older adults. JF - Aging & Mental Health Y1 - 2022 A1 - Thalida E. Arpawong A1 - Mekli, Krisztina A1 - Lee, Jinkook A1 - Drystan F. Phillips A1 - Margaret Gatz A1 - Carol A Prescott KW - adverse child events KW - depression KW - Mental Health KW - stress generation KW - Trauma AB -

We evaluated whether the effects of recent stressful life events (SLEs) and early childhood adversities (ECAs) on depressive symptoms are consistent between men and women and across older age, and whether there was evidence for the following: stress sensitization, whereby the psychological impact of SLEs is greater for individuals with ECAs compared with those without; or stress proliferation effect, whereby those with ECAs are more likely to report more SLEs than those without ECAs to effect depressive symptoms. ECAs, SLEs in the past two years, and current depressive symptoms through a modified CES-D were obtained from 11,873 individuals participating in a population representative study of older adults, yielding 82,764 observations. Mixed-effects regression models on depressive symptoms were constructed to control for multiple observations per participant and evaluate within-person effects over time, thereby reducing bias from reverse causation. Results suggest a stress proliferation effect and do not support stress sensitization. ECAs contribute to vulnerability for depressive symptoms, with a dosage effect for each additional ECA. Recent SLEs result in greater depressive symptom risk, with stable effects over age and dosage effects for each additional SLE that were smaller than the effects of ECAs among men, but not women. Belonging to an ethnic minority group, having less education, and less household income at baseline were associated with greater depressive symptom risk. Findings suggest the importance of addressing early childhood adversity and sociodemographic factors, among at-risk older adults to mitigate life-course stress proliferative processes and thereby reduce disparate risk for depression in older age.

VL - 26 IS - 4 ER - TY - JOUR T1 - Disability Incidence Rates for Men and Women in 23 Countries: Evidence on Health Effects of Gender Inequality. JF - The Journals of Gerontology, Series A Y1 - 2021 A1 - Jinkook Lee A1 - Erik Meijer A1 - Drystan F. Phillips A1 - Hu, Peifeng KW - Activities of Daily Living KW - CHARLS KW - Cross-Country KW - ELSA KW - health disparity KW - KLoSA KW - Longitudinal analysis KW - MHAS KW - SHARE AB -

BACKGROUND: Inequality in gender varies across social contexts, which may influence the health of both men and women. Based on theories of gender as a social system, we examine whether systematic gender inequality at the macro level influences health of men and women.

METHODS: Using harmonized panel data from the Gateway to Global Aging Data in 23 high and middle income countries (N=168,873), we estimate disability prevalence and incidence for men and women ages 55 to 89 (2000-2016). Within each country or geographic region, we also investigate gender differences in age gradients of the probability of disability onset. We, then, pool data from all countries and test the hypothesis that gender inequality increases the probability of disability onset.

RESULTS: We found substantial cross-country variation in disability incidence rates, and this variation is greater for women than for men. Among ages 65-69, disability incidence rates ranged from 0.4 to 5.0 for men and from 0.5 to 9.4 for women. Our within-country analysis showed significant gender differences in age gradients of the probability of disability onset in the U.S., Korea, Southern Europe, Mexico, and China, but not in Northern, Central, and Eastern Europe, England and Israel. Testing hypothesized effects of gender inequality, we find that gender inequality is significantly associated with the probability of disability onset for women, but not for men.

CONCLUSIONS: Macro-level societal gender inequality is significantly associated with the probability of disability onset for women. Reducing and eliminating gender inequality is crucial to achieving good health for women.

VL - 76 IS - 2 ER - TY - JOUR T1 - Frailty Index associates with GRIN2B in two representative samples from the United States and the United Kingdom. JF - PLoS One Y1 - 2018 A1 - Mekli, Krisztina A1 - Stevens, Adam A1 - Alan Marshall A1 - Thalida E. Arpawong A1 - Drystan F. Phillips A1 - Tampubolon, Gindo A1 - Lee, Jinkook A1 - Carol A Prescott A1 - James Nazroo A1 - Pendleton, Neil KW - ELSA KW - Frailty KW - Gene Ontology KW - Genome-Wide Association Study KW - Phenotype AB -

The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways 'Neuropathic pain signalling in dorsal horn neurons' and the 'GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells', exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms.

VL - 13 IS - 11 ER - TY - JOUR T1 - Genome-wide scan of depressive symptomatology in two representative cohorts in the United States and the United Kingdom. JF - Journal of Psychiatric Research Y1 - 2018 A1 - Mekli, Krisztina A1 - Drystan F. Phillips A1 - Thalida E. Arpawong A1 - Vanhoutte, Bram A1 - Tampubolon, Gindo A1 - James Nazroo A1 - Lee, Jinkook A1 - Carol A Prescott A1 - Stevens, Adam A1 - Pendleton, Neil KW - depression KW - ELSA KW - Genome-Wide Association Study AB -

Unlike the diagnosed Major Depressive Disorder, depressive symptomatology in the general population has received less attention in genome-wide association scan (GWAS) studies. Here we report a GWAS study on depressive symptomatology using a discovery-replication design and the following approaches: To improve the robustness of the phenotypic measure, we used longitudinal data and calculated mean scores for at least 3 observations for each individual. To maximize replicability, we used nearly identical genotyping platforms and identically constructed phenotypic measures in both the Discovery and Replication samples. We report one genome-wide significant hit; rs58682566 in the EPG5 gene was associated (p = 3.25E-08) with the mean of the depression symptom in the Discovery sample, without confirmation in the Replication sample. We also report 4 hits exceeding the genome-wide suggestive significance level with nominal replications. Rs11774887, rs4147527 and rs1379328, close to the SAMD12 gene, were associated with the mean depression symptom score (P-values in Discovery sample: 4.58E-06, 7.65E-06 and 7.66E-06; Replication sample: 0.049, 0.029 and 0.030, respectively). Rs13250896, located in an intergenic region, was associated with the mean score of the three somatic items of the depression symptoms score (p = 3.31E-07 and 0.042 for the Discovery and Replication samples). These results were not supported by evidence in the literature. We conclude that despite the strengths of our approach, using robust phenotypic measures and samples that maximize replicability potential, this study does not provide compelling evidence of a single genetic variant's significant role in depressive symptomatology.

VL - 100 ER - TY - RPRT T1 - The Effect of Using Different Imputation Methods for Economic Variables in Aging Surveys Y1 - 2015 A1 - Jinkook Lee A1 - Erik Meijer A1 - Drystan F. Phillips KW - Income KW - Methodology AB - We study the sensitivity of analyses on income and wealth to the methods of imputation for missing data. We do so by implementing a conditional hot-deck imputation, based on the method used by the English Longitudinal Study of Ageing, in the Health and Retirement Study. We compare marginal and joint distributions and regression models estimated from data using these imputations to the same statistics estimated from the RAND HRS data, which use a much more elaborate imputation method, and to estimates from data using an intermediate method. Although many results are qualitatively or quantitatively similar, there are also notable differences. PB - Los Angeles, University of Southern California U4 - missing data/measurement of income and wealth/Health and Retirement Study ER -