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.

Cross-sectional association between posttraumatic stress and cognition is moderated by pulmonary functioning in world trade center responders.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance. METHODS: In this cross-sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma-specific version of the posttraumatic stress disorder checklist (PCL-17) adapted for the WTC attacks. The 1-second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function. RESULTS: Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non-trained (est. = 0.004, 95% C.I. = -0.01, 0.02, p = 0.39) responders. CONCLUSIONS: In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high-risk populations should be studied, especially since intervention in one modality may have an impact on others.

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.

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.

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.

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.

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 Association of Posttraumatic Stress Disorder With Longitudinal Change in Glomerular Filtration Rate in World Trade Center Responders.

OBJECTIVE: High levels of psychological distress increase the risk of a wide range of medical diseases. In this study, we investigated the association between posttraumatic stress disorder (PTSD) and kidney disease. METHODS: World Trade Center (WTC) responders were included if they had two or more measures of estimated glomerular filtration rate (eGFR). The PTSD Checklist (PCL) was used to define no PTSD (PCL < 40), "mild" PTSD (40 ≤ PCL <50), and "severe" PTSD (PCL ≥50). Subtypes of PTSD by symptom clusters were analyzed. Multinomial logistic regression was used to estimate the association of PTSD with two GFR change outcomes (decline or increase) compared with the stable GFR outcome. RESULTS: In 2266 participants, the mean age was 53.1 years, 8.2% were female, and 89.1% were White. Individuals with PTSD (n = 373; 16.5%) did not differ in mean baseline GFR from individuals without PTSD (89.73 versus 90.56 mL min-1 1.73 m-2; p = .29). During a 2.01-year mean follow-up, a mean GFR decline of -1.51 mL min-1 1.73 m-2 per year was noted. In multivariable-adjusted models, PTSD was associated with GFR decline (adjusted relative risk [aRR] = 1.74 [1.32-2.30], p < .001) compared with stable GFR, with "hyperarousal" symptoms showing the strongest association (aRR =2.11 [1.40-3.19]; p < .001). Dose-response effects were evident when comparing mild with severe PTSD and comparing PTSD with versus without depression. PTSD was also associated with GFR rise (aRR = 1.47 [1.10-1.97], p < .009). The association between PTSD and GFR change was stronger in participants older than 50 years. CONCLUSIONS: PTSD may be a novel risk factor for exaggerated longitudinal GFR change in young, healthy adults. These findings need to be validated in other cohorts.

Stability and well-being: Associations among the Big Five domains, metatraits, and three kinds of well-being in a large sample.

OBJECTIVE: The present study estimates associations of the Big Five domains and their metatraits with individual indicators of eudaimonic, hedonic, and social well-being, as well as broader factors that capture the tendency for these individual indicators to correlate. METHOD: Using data from a large sample of adults from the United States, confirmatory factor analysis and exploratory structural equation modeling was used to verify the factor structure of Big Five personality and well-being in adulthood. The factor structure of the Big Five domains and well-being was carried forward to estimate associations between personality and well-being at each of three assessments and different levels of analysis using structural equation modeling. RESULTS: Associations between the Big Five metatraits and well-being were strong and consistent across the three measurements when the average ages of participants were 46, 54, and 63 years. Similar results were observed whether focused on a fine-grained or broad level of analysis. CONCLUSIONS: For all types of well-being, the metatraits accounted for more variance than the Big Five domains, even when the Big Five were operationalized using latent factors, emphasizing the importance of considering this level of analysis when elucidating relations between personality and well-being.

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.

Personal economic anxiety in response to COVID-19.

The economic effects of COVID-19 have been far-reaching. Using a sample of adults from the United States (n = 513), the present study examined demographic and individual correlates of anxiety about financial hardship on March 17th, 2020, the day after historic stock market drops in response to the emerging COVID-19 crisis. Confirmatory factor analysis models determined that a unidimensional approach best accounted for covariation among types of economic anxiety. Zero-order and semi-partial correlations with economic anxiety were estimated. Younger adults tended to report greater anxiety than older adults. Black respondents reported significantly more anxiety, whereas respondents without children living at home reported less anxiety. Low collective self-esteem, low conscientiousness, and low openness to experience were associated with greater economic anxiety. High neuroticism, perceived vulnerability to disease, and belongingness stemming from large group activities also were associated with greater anxiety. The current study provides a first glance at individual differences in understanding who may experience economic anxiety due to the COVID-19 pandemic.

Twin models of environmental and genetic influences on pubertal development, salivary testosterone, and estradiol in adolescence.

OBJECTIVE: Research on sources of variation in adolescent's gonadal hormone levels is limited. We sought to decompose individual differences in adolescent testosterone, estradiol, and pubertal status, into genetic and environmental components. DESIGN: A sample of male and female adolescent twins from the greater Austin and Houston areas provided salivary samples, with a subset of participants providing longitudinal data at 2 waves. PARTICIPANTS: The sample included 902 adolescent twins, 49% female, aged 13-20 years (M = 15.91) from the Texas Twin Project. Thirty-seven per cent of twin pairs were monozygotic; 30% were same-sex dizygotic (DZ) pairs; and 33% were opposite-sex DZ pairs. MEASUREMENTS: Saliva samples were assayed for testosterone and estradiol using chemiluminescence immunoassays. Pubertal status was assessed using self-report. Biometric decompositions were performed using multivariate quantitative genetic models. RESULTS: Genetic factors contributed substantially to variation in testosterone in males and females in the follicular phase of their menstrual cycle (h2  = 60% and 51%, respectively). Estradiol was also genetically influenced in both sexes, but was predominately influenced by nonshared environmental factors. The correlation between testosterone and estradiol was mediated by a combination of genetic and environmental influences for males and females. Genetic and environmental influences on hormonal concentrations were only weakly correlated with self-reported pubertal status, particularly for females. CONCLUSIONS: Between-person variability in adolescent gonadal hormones and their interrelationship reflects both genetic and environmental processes, with both testosterone and estradiol containing sizeable heritable components.

Hair and Salivary Testosterone, Hair Cortisol, and Externalizing Behaviors in Adolescents.

Although testosterone is associated with aggression in the popular imagination, previous research on the links between testosterone and human aggression has been inconsistent. This inconsistency might be because testosterone's effects on aggression depend on other moderators. In a large adolescent sample ( N = 984, of whom 460 provided hair samples), we examined associations between aggression and salivary testosterone, hair testosterone, and hair cortisol. Callous-unemotional traits, parental monitoring, and peer environment were examined as potential moderators of hormone-behavior associations. Salivary testosterone was not associated with aggression. Hair testosterone significantly predicted increased aggression, particularly at low levels of hair cortisol (i.e., Testosterone × Cortisol interaction). This study is the first to examine the relationship between hair hormones and externalizing behaviors and adds to the growing literature that indicates that androgenic effects on human behavior are contingent on aspects of the broader endocrine environment-in particular, levels of cortisol.

Personality risk for antisocial behavior: Testing the intersections between callous-unemotional traits, sensation seeking, and impulse control in adolescence.

The current project seeks to integrate literatures on personality risk for antisocial behavior (ASB) by examining how callous-unemotional traits relate to (a) the development of disinhibited traits and (b) the association between disinhibited traits and ASB. In Study 1, using a nationally representative sample of youth (N > 7,000), we examined whether conduct problems and lack of guilt assessed during ages 4-10 years predicted levels of and changes in disinhibited traits over the course of adolescence, and moderated associations between these traits and ASB. High levels of childhood conduct problems were associated with higher levels of impulsivity, sensation seeking, and ASB in early adolescence, whereas lack of guilt was associated with lower levels of sensation seeking. Neither conduct problems nor lack of guilt significantly predicted changes in impulsivity or sensation seeking, and associations among changes in sensation seeking, impulsivity, and ASB were also consistent across levels of conduct problems and lack of guilt. In Study 2, using a cross-sectional sample of adolescents (N = 970), we tested whether callous-unemotional traits moderated associations between disinhibited traits and ASB. Consistent with the results of Study 1, associations between disinhibited personality and ASB were consistent across a continuous range of callous-unemotional traits.

Sensation seeking and impulsive traits as personality endophenotypes for antisocial behavior: Evidence from two independent samples.

Sensation seeking and impulsivity are personality traits that are correlated with risk for antisocial behavior (ASB). This paper uses two independent samples of twins to (a) test the extent to which sensation seeking and impulsivity statistically mediate genetic influence on ASB, and (b) compare this to genetic influences accounted for by other personality traits. In Sample 1, delinquent behavior, as well as impulsivity, sensation seeking and Big Five personality traits, were measured in adolescent twins from the Texas Twin Project. In Sample 2, adult twins from the Australian Twin Registry responded to questionnaires that assessed individual differences in Eysenck's and Cloninger's personality dimensions, and a structured telephone interview that asked participants to retrospectively report DSM-defined symptoms of conduct disorder. Bivariate quantitative genetic models were used to identify genetic overlap between personality traits and ASB. Across both samples, novelty/sensation seeking and impulsive traits accounted for larger portions of genetic variance in ASB than other personality traits. We discuss whether sensation seeking and impulsive personality are causal endophenotypes for ASB, or merely index genetic liability for ASB.

Genes Unite Executive Functions in Childhood.

Individual differences in children's executive functions (EFs) are relevant for a wide range of normal and atypical psychological outcomes across the life span, but the origins of variation in children's EFs are not well understood. We used data from a racially and socioeconomically diverse sample of 505 third- through eighth-grade twins and triplets from the Texas Twin Project to estimate genetic and environmental influences on a Common EF factor and on variance unique to four core EF domains: inhibition, switching, working memory, and updating. As has been previously demonstrated in young adults, the Common EF factor was 100% heritable, which indicates that correlations among the four EF domains are entirely attributable to shared genetic etiology. Nonshared environmental influences were evident for variance unique to individual domains. General EF may thus serve as an early life marker of genetic propensity for a range of functions and pathologies later in life.

Developmental changes in genetic and environmental influences on rule-breaking and aggression: age and pubertal development.

BACKGROUND: Antisocial behavior (ASB) can be meaningfully divided into nonaggressive rule-breaking versus aggressive dimensions, which differ in developmental course and etiology. Previous research has found that genetic influences on rule-breaking, but not aggression, increase from late childhood to mid-adolescence. This study tested the extent to which the developmental increase in genetic influence on rule-breaking was associated with pubertal development compared to chronological age. METHOD: Child and adolescent twins (n = 1,031), ranging in age from 8 to 20 years (M age = 13.5 years), were recruited from public schools as part of the Texas Twin Project. Participants reported on their pubertal development using the Pubertal Development Scale and on their involvement in ASB on items from the Child Behavior Checklist. Measurement invariance of ASB subtypes across age groups (≤12 years vs. >12 years old) was tested using confirmatory factor analyses. Quantitative genetic modeling was used to test whether the genetic and environmental influences on aggression and rule-breaking were moderated by age, pubertal status, or both. RESULTS: Quantitative genetic modeling indicated that genetic influences specific to rule-breaking increased as a function of pubertal development controlling for age (a gene × puberty interaction), but did not vary as a function of age controlling for pubertal status. There were no developmental differences in the genetic etiology of aggression. Family-level environmental influences common to aggression and rule-breaking decreased with age, further contributing to the differentiation between these subtypes of ASB from childhood to adolescence. CONCLUSIONS: Future research should discriminate between alternative possible mechanisms underlying gene × puberty interactions on rule-breaking forms of antisocial behavior, including possible effects of pubertal hormones on gene expression.

Person × Environment Interactions on Adolescent Delinquency: Sensation Seeking, Peer Deviance and Parental Monitoring.

Sensation seeking is a personality trait that is robustly correlated with delinquent behavior in adolescence. The current study tested specific contextual factors hypothesized to facilitate, exacerbate or attenuate this risk factor for adolescent delinquency. Individual differences in sensation seeking, peer deviance, parental monitoring and self-reported delinquent behavior were assessed in a sample of 470 adolescents. Peer deviance partially mediated the effects of sensation seeking and parental monitoring on adolescent delinquency. We also found evidence for a three-way interaction between sensation seeking, peer deviance and parental monitoring, such that the highest rates of delinquency occurred from the concurrence of high sensation seeking, high peer deviance, and low levels of parental monitoring. Results highlight the importance of considering peer- and family-level processes when evaluating personality risk and problematic adolescent behavior.