A novel approach to model cumulative stress: Area under the s-factor curve.

OBJECTIVE: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. METHOD: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. RESULTS: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. CONCLUSIONS: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.

Linking genetic foundations of sleep disturbances to personality traits: a study of mid-life twins.

Risk of sleep disturbances depends on individuals' personality, and a large body of evidence indicates that individuals prone to neuroticism, impulsivity, and (low) extraversion are more likely to experience them. Origins of these associations are unclear, but common genetic background may play an important role. Participants included 405 twin pairs (mean age of 54 years; 59% female) from the National Survey of Midlife Development in the United States (MIDUS) who reported on their personality traits (broad and specific), as well as sleep disturbances (problems with falling asleep, staying asleep, waking early, and feeling unrested). Uni- and bivariate biometric decompositions evaluated contributions of genetic and environmental factors to associations between personality and poor sleep, as well as unique contributions from individual traits. Neuroticism, extraversion, conscientiousness, and aggressiveness were the strongest phenotypic predictors of poor sleep. Genetic sources of covariance were about twice as large as non-shared environmental sources, and only shared genetic background accounted for links between aggressiveness and poor sleep. Neuroticism and extraversion accounted for most of the genetic overlap between personality and sleep disturbances. The findings shed light on developmental antecedents of ties between personality and poor sleep, suggesting a larger role of common genetic background than idiosyncratic life experiences. The results also suggest that emotion-related traits play the most important role for poor sleep, compared to other personality traits, and may partially account for genetic associations with other traits.

Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

Cohort Changes and Sex Differences After Age 50 in Cognitive Variables in the English Longitudinal Study of Ageing.

OBJECTIVES: This paper models cognitive aging, across mid and late life, and estimates birth cohort and sex differences in both initial levels and aging trajectories over time in a sample with multiple cohorts and a wide span of ages. METHODS: The data used in this study came from the first 9 waves of the English Longitudinal Study of Ageing, spanning 2002-2019. There were n = 76,014 observations (proportion male 45%). Dependent measures were verbal fluency, immediate recall, delayed recall, and orientation. Data were modeled using a Bayesian logistic growth curve model. RESULTS: Cognitive aging was substantial in 3 of the 4 variables examined. For verbal fluency and immediate recall, males and females could expect to lose about 30% of their initial ability between the ages of 52 and 89. Delayed recall showed a steeper decline, with males losing 40% and females losing 50% of their delayed recall ability between ages 52 and 89 (although females had a higher initial level of delayed recall). Orientation alone was not particularly affected by aging, with less than a 10% change for either males or females. Furthermore, we found cohort effects for initial ability level, with particularly steep increases for cohorts born between approximately 1930 and 1950. DISCUSSION: These cohort effects generally favored later-born cohorts. Implications and future directions are discussed.

It Runs in the Family: Testing for Longitudinal Family Flynn Effects.

The Flynn effect refers to increases over time in measured (particularly fluid) intelligence of approximately 3 IQ points per decade. We define the Flynn effect at the family level, using longitudinal data and two new family-level cohort definitions. Multilevel growth curve analyses of the National Longitudinal Survey of Youth 1979 data showed that children in families with later-born mothers had higher average PIAT math scores, and lower average reading comprehension scores and growth, in young and middle childhood. Children in families where the first child was born later had higher average PIAT math, reading recognition, and reading comprehension scores, as well as larger developmental growth. The latter family-level Flynn effects were of higher magnitudes than the usual individual-level Flynn effect found in previous studies. Our results, showing family level-intercept and slope Flynn effects for both maternal birthyear and first child birthyear, have implications for research aiming to explain the Flynn effect.

Genetic Liability, Exposure Severity, and Post-Traumatic Stress Disorder Predict Cognitive Impairment in World Trade Center Responders.

BACKGROUND: There is a high incidence of cognitive impairment among World Trade Center (WTC) responders, comorbid with post-traumatic stress disorder (PTSD). Yet, it remains unknown whether genetic liability for Alzheimer's disease, PTSD, educational attainment, or for a combination of these phenotypes, is associated with cognitive impairment in this high-risk population. Similarly, whether the effects of genetic liability are comparable to PTSD and indicators of exposure severity remains unknown. OBJECTIVE: In a study of 3,997 WTC responders, polygenic scores for Alzheimer's disease, PTSD, and educational attainment were used to test whether genome-wide risk for one or more of these phenotypes is associated with cognitive impairment, controlling for population stratification, while simultaneously estimating the effects of demographic factors and indicators of 9/11 exposure severity, including symptoms of PTSD. RESULTS: Polygenic scores for Alzheimer's disease and educational attainment were significantly associated with an increase and decrease, respectively, in the hazard rate of mild cognitive impairment. The polygenic score for Alzheimer's disease was marginally associated with an increase in the hazard rate of severe cognitive impairment, but only age, exposure severity, and symptoms of PTSD were statistically significant predictors. CONCLUSION: These results add to the emerging evidence that many WTC responders are suffering from mild cognitive impairments that resemble symptoms of Alzheimer's disease, as genetic liability for Alzheimer's disease predicted incidence of mild cognitive impairment. However, compared to polygenic scores, effect sizes were larger for PTSD and the type of work that responders completed during rescue and recovery efforts.

Discrimination Exposure and Polygenic Risk for Obesity in Adulthood: Testing Gene-Environment Correlations and Interactions.

INTRODUCTION: Exposure to discrimination has emerged as a risk factor for obesity. It remains unclear, however, whether the genotype of the individual can modulate the sensitivity or response to discrimination exposure (gene × environment interaction) or increase the likelihood of experiencing discrimination (gene-environment correlation). METHODS: This was an observational study of 4,102 white/European Americans in the Health and Retirement Study with self-reported, biological assessments, and genotyped data from 2006 to 2014. Discrimination was operationalized using the average of nine Everyday Discrimination Scale items. Polygenic risk scores (PRSs) for body mass index (BMI) and waist circumference (WC) were calculated using the weighted sum of risk alleles based on studies conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. RESULTS: We found that greater PRS-BMI was significantly associated with more reports of discrimination (ß = 0.04 ± 0.02; p = 0.037). Further analysis showed that measured BMI partially mediated the association between PRS-BMI and discrimination. There was no evidence that the association between discrimination and BMI, or the association between discrimination and WC, differed by PRS-BMI or PRS-WC, respectively. CONCLUSION: Our findings suggest that individuals with genetic liability for obesity may experience greater discrimination in their lifetime, consistent with a gene-environment correlation hypothesis. There was no evidence of a gene-environment interaction. More genome-wide association studies in diverse populations are needed to improve generalizability of study findings. In the meantime, prevention and clinical intervention efforts that seek to reduce exposure to all forms of discrimination may help reduce obesity at the population level.

Pathological personality in relation to multiple domains of quality of life and impairment: Evidence for the specific relevance of the maladaptive poles of major trait domains.

The current study examined whether personality domains have nonmonotonic relationships with functional outcomes, specifically in relation to quality of life and impairment. Four samples were utilized, which were drawn from the United States and Germany. Personality trait domains were measured via the IPIP-NEO and PID-5; quality of life (QoL) was measured with the WHOQOL-BREF, and impairment was measured using the WHODAS-2.0. The PID-5 was analyzed in all four samples. Two-line testing, which fits two spline regression lines separated at a break point, was conducted to evaluate potential nonmonotonicity of the relationship between personality traits and quality of life. Overall, results demonstrated little support for nonmonotonic relationships in the PID-5 and IPIP-NEO dimensions. Rather, our results indicate that there is one clear pathological pole of major domains of personality that is associated with lower quality of life and increased impairment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Intersectional vulnerability in the relationship between discrimination and inflammatory gene expression.

Addressing social disparities in health and well-being requires understanding how the effects of discrimination become biologically embedded, and how embedding processes might vary across different demographic contexts. Emerging research suggests that a threat-related gene expression response may contribute to social disparities in health. We tested a contextual vulnerability model of discrimination embedding using an empirical intersectionality (interaction discovery) analysis of pro-inflammatory gene expression in a national sample of non-institutionalized, English-speaking adults with RNA biomarker data (n = 543). At the time of data collection, the average age of participants was 55 years (SD = 13.26) and approximately half identified as female (50.46%). Most participants identified as White (∼73%) and had some college experience (∼60%). Results showed significant variation in the strength of association between daily discrimination and inflammatory gene expression by race and sex (b = -0.022; 95% CI:-0.038,-0.005, p = .009) with the estimated marginal association larger for racially-minoritized males (b = 0.007; 95% CI:-0.003,0.017, p = .163), compared to White males (b = -0.006; 95% CI:-0.013,0.001, p = .076). This study indicates that the link between daily discrimination and inflammatory gene expression may vary by sociodemographic characteristics. To improve initiatives and policies aimed at ameliorating disparities within populations, greater attention is needed to understand how interlocking systems of inequalities contribute to physiological health.

A Mixed-Methods Approach to Refining and Measuring the Construct of Positive Risk-Taking in Adolescence.

Adolescence is a peak period for risk-taking, but research has largely overlooked positive manifestations of adolescent risk-taking due to ambiguity regarding operationalization and measurement of positive risk-taking. We address this limitation using a mixed-methods approach. We elicited free responses from contemporary college students (N = 74, Mage  = 20.1 years) describing a time they took a risk. Qualitative analysis informed the construction of a self-report positive risk-taking scale, which was administered to a population-based sample of adolescents (N = 1,249, Mage  = 16 years) for quantitative validation and examination of associations with normative and impulsive personality. Sensation seeking predicted negative and positive risk-taking, whereas extraversion and openness were predominantly related to positive risk-taking. Results provide promising evidence for a valid measure of adolescents' engagement in positive risks.

Comparing associations between personality and loneliness at midlife across three cultural groups.

OBJECTIVE: Loneliness represents a public health threat given its central role in predicting adverse mental and physical health outcomes. Prior research has established four of the Big Five personality traits as consistent cross-sectional predictors of loneliness in largely western, White samples. However, it is not clear if the personality predictors of loneliness vary across cultures. METHOD: The present study estimates associations between the Big Five traits and loneliness across distinct samples of White American, Black American, and Japanese adults (n = 6051 at T1). Confirmatory factor analysis and exploratory structural equation modeling were used to examine measurement invariance properties of the Big Five and loneliness across these groups. The factor structures were then carried forward to estimate associations between personality and loneliness across two assessments waves using structural equation modeling. RESULTS: While Neuroticism was a strong predictor across groups, low Extraversion was more predictive of loneliness in Japan than in the U.S., and low Conscientiousness was only a significant predictor in the U.S. CONCLUSIONS: Previous literature offers a framework for interpreting these findings in that loneliness may be shaped comparatively more through interconnectedness in Japanese culture, while, in the U.S., individual goals and personal romantic expectations are more salient.

Comparing Phenotypic, Genetic, and Environmental Associations between Personality and Loneliness.

As a strong risk factor for mortality, individual differences in loneliness are of clear public health significance. Four of the Big Five traits have emerged as cross-sectional correlates, but the etiology of these links is unclear, as are relations with more specific personality facets. Thus, we estimated phenotypic, genetic, and environmental associations between loneliness and both broader and narrower personality dimensions. Traits that indexed Negative Emotionality (e.g., Neuroticism, Stress Reactivity, Alienation) and low Positive Emotionality (e.g., low Extraversion, low Well-Being) had the strongest associations with loneliness, though low Conscientiousness, low Agreeableness, and high Aggression were also implicated. These associations were explained by both genetic (0.30<|rg|<0.80) and unique environmental (0.10<|re|<0.35) influences, consistent with an etiology of loneliness involving several personality domains.

Polygenic association of glomerular filtration rate decline in world trade center responders.

BACKGROUND: The factors associated with estimated glomerular filtrate rate (eGFR) decline in low risk adults remain relatively unknown. We hypothesized that a polygenic risk score (PRS) will be associated with eGFR decline. METHODS: We analyzed genetic data from 1,601 adult participants with European ancestry in the World Trade Center Health Program (baseline age 49.68 ± 8.79 years, 93% male, 23% hypertensive, 7% diabetic and 1% with cardiovascular disease) with ≥ three serial measures of serum creatinine. PRSs were calculated from an aggregation of single nucleotide polymorphisms (SNPs) from a recent, large-scale genome-wide association study (GWAS) of rapid eGFR decline. Generalized linear models were used to evaluate the association of PRS with renal outcomes: baseline eGFR and CKD stage, rate of change in eGFR, stable versus declining eGFR over a 3-5-year observation period. eGFR decline was defined in separate analyses as "clinical" (> -1.0 ml/min/1.73 m2/year) or "empirical" (lower most quartile of eGFR slopes). RESULTS: The mean baseline eGFR was ~ 86 ml/min/1.73 m2. Subjects with decline in eGFR were more likely to be diabetic. PRS was significantly associated with lower baseline eGFR (B = -0.96, p = 0.002), higher CKD stage (OR = 1.17, p = 0.010), decline in eGFR (OR = 1.14, p = 0.036) relative to stable eGFR, and the lower quartile of eGFR slopes (OR = 1.21, p = 0.008), after adjusting for established risk factors for CKD. CONCLUSION: Common genetic variants are associated with eGFR decline in middle-aged adults with relatively low comorbidity burdens.

The weight of childhood adversity: evidence that childhood adversity moderates the impact of genetic risk on waist circumference in adulthood.

OBJECTIVE: The present study tested the interactive effects of childhood adversity and polygenic risk scores for waist circumference (PRS-WC) on waist circumference (WC). Consistent with a diathesis-stress model, we hypothesize that the relationship between PRS-WC and WC will be magnified by increasing levels of childhood adversity. METHODS: Observational study of 7976 adults (6347 European Americans and 1629 African Americans) in the Health and Retirement Study with genotyped data. PRS-WC were calculated by the HRS administrative core using the weighted sum of risk alleles based on a genome-wide association study conducted by the Genetic Investigation of Anthropometric Traits (GIANT) consortium. Childhood adversity was operationalized using a sum score of three traumatic events that occurred before the age of 18 years. RESULTS: There was a statistically significant interaction between PRS-WC and childhood adversity for European Americans, whereby the magnitude of PRS-WC predicting WC increased as the number of adverse events increased. CONCLUSIONS: This study supports the idea of the interactive effects of genetic risks and childhood adversity on obesity. More epidemiological studies, particularly with understudied populations, are needed to better understand the roles that genetics and childhood adversity play on the development and progression of obesity.

Getting a Grip on Secular Changes: Age-Period-Cohort Modeling of Grip Strength in the English Longitudinal Study of Ageing.

BACKGROUND: Grip strength is a popular and valuable measure in studies of physical functional capabilities in old age. The influence of historical trends and differential period-specific exposures can complicate the interpretation of biomarkers of aging and health and requires careful analysis and interpretation of aging, birth cohort, and period effects. This study evaluates the effects of aging, period, and cohort on grip strength in a population of adults and older adults. METHODS: We use more than 27 000 observations for individuals at least 50 years of age, born in approximately 1910-1960, from the English Longitudinal Study of Ageing to examine a variety of multilevel and cross-classified modeling approaches to evaluate age, period, and cohort effects. Our results extended Hierarchical Age-Period-Cohort modeling and compared our results with a set of 9 submodels with explicit assumptions to determine the most reliable modeling approach. RESULTS: Findings suggest grip strength is primarily related to age, with minimal evidence of either period and/or cohort effects. Each year's increase in a person's age was associated with a 0.40-kg decrease in grip strength, though this decline differs by gender. CONCLUSIONS: We conclude that as the population ages, grip strength declines at a systematic and predictable rate equal to -0.40 kg per year (approximately -0.50 kg for men and -0.30 kg for women) in residents of England aged 50 and older. Age effects were predominant and most consistent across methodologies. While there was some evidence for cohort effects, such effects were minimal and therefore indicative that grip strength is a consistent physiological biomarker of aging.

Cumulative stress: A general "s" factor in the structure of stress.

OBJECTIVE: The present study tested a hierarchical model of cumulative stress in a large probability sample of adults from the United States. METHODS: Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) models were used to develop and test a hierarchical model of cumulative stress. Structural equation models were used to estimate concurrent associations with demographic factors, polygenic risk scores, and physical health outcomes, as well as prospective associations with physical health outcomes. RESULTS: A hierarchical model of cumulative stress was the best-fitting model, with a general "s-factor" capturing the tendency for subordinate dimensions of stress to correlate. Associations with demographic factors and polygenic risk scores for physical and psychological phenotypes provide evidence for the convergent validity of a general s-factor of cumulative stress. The general s-factor and subordinate factors of cumulative stress were also associated with physical health outcomes, concurrently and prospectively, including number of chronic conditions, body mass index, and difficulty with activities of daily living. CONCLUSIONS: Like other human individual differences, the co-occurrence of social stressors can be understood using a hierarchical model.

Patterns of cumulative continuity and maturity in personality and well-being: Evidence from a large longitudinal sample of adults.

Longitudinal studies have shown that, on average, agreeableness and conscientiousness increase and neuroticism decreases in adulthood, a phenomenon dubbed the "maturity principle". The rank-order stability of personality also tends to increase with age, sometimes called the "cumulative continuity principle". It remains unclear, however, whether the rank-order stability and average levels of different types of well-being increase with age. Therefore, using a large longitudinal sample of adults (N > 6,000), the present study aimed to replicate studies of the maturity and cumulative continuity of the Big Five and test whether these developmental trends extend to different types of well-being. The present study demonstrates that, although many types of well-being exhibit developmental trends that are similar to those of the Big Five, distinguishing the general tendency toward all forms of well-being from variation in specific kinds of well-being can illuminate potentially important developmental differences.

Big Five Personality and CTRA gene expression: Lack of association in a midlife sample of US adults (MIDUS-Refresher).

A previous study found that Extraversion and Conscientiousness were associated with increased and decreased expression of a pre-specified set of pro-inflammatory indicator genes. The present study aimed to replicate these findings in a sample of adults from the Refresher Cohort of the Study of Midlife in the United States (MIDUS). Analysis of gene expression composite scores and generalized linear models that took into account the heterogeneity and non-independence of RNA expression across different genes found no significant associations between the pro-inflammatory indicator gene set and the Big Five domains of personality. In addition, there was no significant association between a pre-specified antiviral indicator gene set and the Big Five domains. These findings suggest that relations between Big Five personality and expression of these two immune response indicator gene sets do not consistently appear across samples and may be context-dependent in ways that remain to be elucidated.

Discrimination and anxiety: Using multiple polygenic scores to control for genetic liability.

An established body of research indicates that discrimination is associated with increased symptoms of anxiety and negative affect. However, the association cannot be interpreted unambiguously as an exposure effect because a common set of genetic factors can simultaneously contribute to increased liability for symptoms of anxiety, negative affect, and the perception of discrimination. The present study elucidates the association between discrimination and anxiety/negative affect by implementing strict genetic controls in a large sample of adults. We used data from the biomarker project of the Study of Midlife Development in the United States (MIDUS), a national probability sample of noninstitutionalized, English-speaking respondents aged 25 to 74 y. Participants who consented to provide genetic data were biologically unrelated and of European ancestry as determined by genotype principal components analysis (n = 1,146). A single structural regression model was fit to the data with three measures of discrimination specified to load onto a latent factor and six measures of anxiety and negative affect specified to load onto a second latent factor. After accounting for potential genetic confounds-polygenic scores for anxiety, depression, and neuroticism and the first five genetic principal components-greater discrimination was associated with greater anxiety/negative affect (ß = 0.53, SE = 0.04, P < 0.001). Findings suggest that measures of perceived discrimination should be considered environmental risk factors for anxiety/negative affect rather than indices of genetic liability for anxiety, depression, or neuroticism. Clinical interventions and prevention measures should focus on ways to mitigate the impact of discrimination to improve mental health at the population level.

Marital Satisfaction as a Moderator of Molecular Genetic Influences on Mental Health.

The quality of one's romantic relationship is associated with mental health. Low levels of relationship quality may be a stressor that triggers a predisposition or diathesis to mental illness. Analyses were conducted to examine whether relationship quality moderated the association between polygenic risk scores (PRSs) for several mental health syndromes on phenotypic measures of those syndromes. Data were drawn from the Midlife in the United States (MIDUS) study of health and well-being. A subsample was genotyped, and PRSs were calculated. The PRS for anxiety was more strongly related to the anxiety phenotype when satisfaction was low than when satisfaction was high, providing evidence of a genetic susceptibility process between marital distress and anxiety. The expression of genetic influences on a phenotype in the presence of certain environmental stressors is complex and may depend on the specific phenotype and the methodology by which genetic influences are estimated.