Phenotypic and Genetic Markers of Psychopathology in a Population-Based Sample of Older Adults

AbstractAlthough psychiatric phenotypes are hypothesized to organize into a two-factor internalizing – externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6,216 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered GWAS. Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, ADHD) were not associated with any phenotypes, PGSs for MDD, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the latent internalizing PGS and the latent one-factor PGS, derived using weights from Genomic SEM, explained 1% more variance in the general factor of psychopathology than any of the individual PGSs. Results support the following conclusions: genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in European ancestries, GWAS-derived PGSs fail to capture genetic variation associated with disease specificity in European ancestries, and blunt phenotypic measurement in GWAS may preclude our ability to evaluate the structure and specificity of genetic contributions to psychiatric disorders.

Download Full-text

Phenotypic and genetic markers of psychopathology in a population-based sample of older adults

Translational Psychiatry ◽

10.1038/s41398-021-01354-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Arianna M. Gard ◽

Erin B. Ware ◽

Luke W. Hyde ◽

Lauren L. Schmitz ◽

Jessica Faul ◽

...

Keyword(s):

Older Adults ◽

Large Population ◽

The United States ◽

Population Based ◽

European Ancestry ◽

Equation Modeling ◽

General Factor ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Polygenic Scores

AbstractAlthough psychiatric phenotypes are hypothesized to organize into a two-factor internalizing–externalizing structure, few studies have evaluated the structure of psychopathology in older adults, nor explored whether genome-wide polygenic scores (PGSs) are associated with psychopathology in a domain-specific manner. We used data from 6003 individuals of European ancestry from the Health and Retirement Study, a large population-based sample of older adults in the United States. Confirmatory factor analyses were applied to validated measures of psychopathology and PGSs were derived from well-powered genome-wide association studies (GWAS). Genomic SEM was implemented to construct latent PGSs for internalizing, externalizing, and general psychopathology. Phenotypically, the data were best characterized by a single general factor of psychopathology, a factor structure that was replicated across genders and age groups. Although externalizing PGSs (cannabis use, antisocial behavior, alcohol dependence, attention deficit hyperactivity disorder) were not associated with any phenotypes, PGSs for major depressive disorder, neuroticism, and anxiety disorders were associated with both internalizing and externalizing phenotypes. Moreover, the variance explained in the general factor of psychopathology increased by twofold (from 1% to 2%) using the latent internalizing or latent one-factor PGSs, derived using weights from Genomic Structural Equation Modeling (SEM), compared with any of the individual PGSs. Collectively, results suggest that genetic risk factors for and phenotypic markers of psychiatric disorders are transdiagnostic in older adults of European ancestry. Alternative explanations are discussed, including methodological limitations of GWAS and phenotypic measurement of psychiatric outcome in large-scale population-based studies.

Download Full-text

The epidemiology of atopic dermatitis in older adults: A population-based study in the United Kingdom

PLoS ONE ◽

10.1371/journal.pone.0258219 ◽

2021 ◽

Vol 16 (10) ◽

pp. e0258219

Author(s):

Leslie N. Chan ◽

Alexa Magyari ◽

Morgan Ye ◽

Noor A. Al-Alusi ◽

Sinead M. Langan ◽

...

Keyword(s):

Older Adults ◽

Atopic Dermatitis ◽

United Kingdom ◽

Older Adult ◽

Large Population ◽

Age Groups ◽

Population Based ◽

Diagnostic Code ◽

The United Kingdom ◽

Over Time

Background Atopic dermatitis is known to be common among children, but there are few studies examining the epidemiology across the life course. In particular, there is a paucity of data on atopic dermatitis among older adults. Objective To evaluate participant characteristics, patterns of disease activity and severity, and calendar trends in older adult atopic dermatitis in comparison to other age groups in a large population-based cohort. Methods This was a cohort study of 9,154,936 individuals aged 0–99 years registered in The Health Improvement Network, a database comprised of electronic health records from general practices in the United Kingdom between 1994 and 2013. Atopic dermatitis was defined by a previously validated algorithm using a combination of at least one recorded atopic dermatitis diagnostic code in primary care and two atopic dermatitis therapies recorded on separate days. Cross-sectional analyses of disease prevalence were conducted at each age. Logistic mixed effect regression models were used to identify predictors of prevalent disease over time among children (0–17 years), adults (18–74 years), and older adults (75–99 years). Results Physician-diagnosed atopic dermatitis was identified in 894,454 individuals with the following proportions in each age group: 18.3% of children, 7.7% of adults, and 11.6% of older adults. Additionally, atopic dermatitis prevalence increased across the 2-decade period (beta from linear regression test for trend in the change in proportion per year = 0.005, p = 0.044). In older adults, atopic dermatitis was 27% less common among females (adjusted OR 0.73, 95% CI 0.70–0.76) and was more likely to be active (59.7%, 95% CI 59.5–59.9%) and of higher severity (mean annual percentage with moderate and severe disease: 31.8% and 3.0%, respectively) than in other age groups. Conclusion In a large population-based cohort, the prevalence of physician-diagnosed atopic dermatitis has increased throughout adulthood and was most common among males age 75 years and above. Compared to children ages 0–17 and adults ages 18–74, older adult atopic dermatitis was more active and severe. Because the prevalence of atopic dermatitis among older adults has increased over time, additional characterization of disease triggers and mechanisms and targeted treatment recommendations are needed for this population.

Download Full-text

The German Version of the Satisfaction With Life Scale (SWLS)

European Journal of Psychological Assessment ◽

10.1027/1015-5759/a000058 ◽

2011 ◽

Vol 27 (2) ◽

pp. 127-132 ◽

Cited By ~ 180

Author(s):

Heide Glaesmer ◽

Gesine Grande ◽

Elmar Braehler ◽

Marcus Roth

Keyword(s):

Convergent Validity ◽

Satisfaction With Life ◽

Age Groups ◽

Population Based ◽

Factorial Invariance ◽

Satisfaction With Life Scale ◽

Small Samples ◽

Cross Sectional ◽

Confirmatory Factor Analyses ◽

Life Scale

The Satisfaction with Life Scale (SWLS) is the most commonly used measure for life satisfaction. Although there are numerous studies confirming factorial validity, most studies on dimensionality are based on small samples. A controversial debate continues on the factorial invariance across different subgroups. The present study aimed to test psychometric properties, factorial structure, factorial invariance across age and gender, and to deliver population-based norms for the German general population from a large cross-sectional sample of 2519 subjects. Confirmatory factor analyses supported that the scale is one-factorial, even though indications of inhomogeneity of the scale have been detected. Both findings show invariance across the seven age groups and both genders. As indicators of the convergent validity, a positive correlation with social support and negative correlation with depressiveness was shown. Population-based norms are provided to support the application in the context of individual diagnostics.

Download Full-text

Faculty Opinions recommendation of Use of radiation therapy in the last 30 days of life among a large population-based cohort of elderly patients in the United States.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717976757.793470519 ◽

2013 ◽

Author(s):

Noelle LoConte ◽

Ticiana Leal

Keyword(s):

United States ◽

Radiation Therapy ◽

Elderly Patients ◽

Large Population ◽

The United States ◽

Population Based

Download Full-text

Abstract 88: Increasing False Positive Diagnoses May Lead to Overestimation of Stroke Incidence, Particularly in the Young

Stroke ◽

10.1161/str.51.suppl_1.88 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Abhinav J Appukutty ◽

Lesli E Skolarus ◽

Mellanie V Springer ◽

William J Meurer ◽

James F Burke

Keyword(s):

Older Adults ◽

False Positive ◽

Age Groups ◽

Vascular Risk Factor ◽

The United States ◽

Cross Sectional ◽

Stroke Incidence ◽

Ed Visits ◽

Over Time

Introduction: Stroke incidence is reportedly increasing in younger adults. While increasing vascular risk factor prevalence has been suggested as a cause, the reasons for rising stroke incidence in the young are not clear. We explored several alternate explanations: trends in neurologically-focused emergency department (ED) visits, differential diagnostic classification of stroke and TIA over time, and changes in the use of advanced imaging in young and older adults. Methods: We performed a retrospective, serial, cross-sectional study on a nationally representative sample of all ED visits in the United States to quantify changes in patterns of neurologically-focused ED visits, stroke and TIA diagnoses, and rates of MRI utilization for young (18 – 44 years) and older (65+ years) adults over a 17-year period (1995 – 2000; 2005 – 2015) using National Hospital Ambulatory Medical Care Survey (NHAMCS) data. Results: In young adults, 0.4% (95% CI 0.3% – 0.5%) of neurologically-focused ED visits resulted in a primary diagnosis of stroke vs. 6.8% (95% CI 6.2% – 7.5%) for older adults. In both populations, the incidence of neurologically-focused ED visits has increased over time (+111/100,000 population/year, 95% CI +94 – +130 in the young vs. +70/100,000 population/year, 95% CI +34 – +108 in older adults). There was no evidence of differential classification of TIA to stroke over time (OR 1.001 per year, 95% CI 0.926 – 1.083 in the young; OR 1.003 per year, 95% CI 0.982 – 1.026 in older adults) and no evidence of disproportionate rise in MRI utilization for neurologically-focused ED visits in the young (OR 1.057 per year, 95% CI 1.028 – 1.086 in the young; OR 1.095 per year, 95% CI 1.066 – 1.125 in older adults). Conclusions: If the specificity of stroke diagnosis amongst ED visits is similar amongst young and older populations, then the combination of data observed here, including (1) a lower prior probability of stroke diagnoses in the young and (2) an increasing trend in neurologically-focused ED visits in both age groups, suggests that false positive diagnoses will increase over time, with a faster rise in the young compared to older adults. These data suggest a potential explanation that may contribute to higher stroke incidence in the young and merits further scrutiny.

Download Full-text

THE PROTECTIVE ROLE OF SOCIAL SUPPORT ON DEPRESSIVE SYMPTOMS AMONG AGING SEXUAL MINORITY CANADIANS

Innovation in Aging ◽

10.1093/geroni/igz038.1113 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S303-S304

Author(s):

Arne Stinchcombe ◽

Nicole G Hammond ◽

Kimberley Wilson

Keyword(s):

Social Support ◽

Older Adults ◽

Depressive Symptoms ◽

Sexual Orientation ◽

Sexual Minority ◽

Large Population ◽

Population Based ◽

Protective Role ◽

Linear Regression Models ◽

And Bisexual

Abstract Sexual minority older adults face minority stressors that are associated with higher rates of mental illness. The stress buffering effects of social support within majority populations are well documented. Using a large population-based sample of aging Canadians, we sought to examine the relationship between sexual orientation and depressive symptoms, and determine whether this relationship is moderated by social support and sex. Baseline data from the Canadian Longitudinal Study on Aging (CLSA) were used (n = 46147). Participants were between the ages of 45-85 years at time of recruitment (mean age = 62.46, SD = 10.27), and self-reported their sexual orientation as heterosexual or lesbian, gay, or bisexual (LGB) (2.1%). Social support and depressive symptoms were measured using validated instruments. Four functional social support subscales were derived: tangible, positive social interaction, affectionate, and emotional/informational. Multiple linear regression models adjusted for relevant covariates were conducted. LGB identification was associated with greater depressive symptoms when compared to heterosexual participants (p = 0.032). As evidenced by a significant 3-way interaction (p = 0.030), increasing tangible social support was associated with a corresponding decrease in the risk of depressive symptoms; this relationship was most pronounced for lesbian and bisexual women. A significant 2-way interaction (p = 0.040) revealed that as emotional/informational social support increased, depressive symptoms decreased, with greater disparity between LGB and heterosexual participants at lower levels of social support. The results highlight the importance of social support in promoting mental health, especially among sexual minority older adults.

Download Full-text

Healthy aging profile in octogenarians in Brazil

Revista Latino-Americana de Enfermagem ◽

10.1590/1518-8345.0694.2724 ◽

2016 ◽

Vol 24 (0) ◽

Cited By ~ 3

Author(s):

Ana Cristina Viana Campos ◽

Efigênia Ferreira e Ferreira ◽

Andréa Maria Duarte Vargas ◽

Lúcia Hisako Takase Gonçalves

Keyword(s):

Older Adults ◽

Decision Tree ◽

Healthy Aging ◽

Age Groups ◽

Population Based ◽

P Value ◽

Age Group ◽

Monthly Income ◽

Tree Model ◽

Socioeconomic Characteristics

ABSTRACT Objective: to identify the healthy aging profile in octogenarians in Brazil. Method: this population-based epidemiological study was conducted using household interviews of 335 octogenarians in a Brazilian municipality. The decision-tree model was used to assess the healthy aging profile in relation to the socioeconomic characteristics evaluated at baseline. All of the tests used a p-value < 0.05. Results: the majority of the 335 participating older adults were women (62.1%), were aged between 80 and 84 years (50.4%), were widowed (53.4%), were illiterate (59.1%), had a monthly income of less than one minimum wage (59.1%), were retired (85.7%), lived with their spouse (63.8%), did not have a caregiver (60.3%), had two or more children (82.7%), and had two or more grandchildren (78.8%). The results indicate three age groups with a healthier aging profile: older adults aged 80 to 84 years (55.6%), older adults aged 85 years and older who are married (64.9%), and older adults aged 85 and older who do not have a partner or a caregiver (54.2%). Conclusion: the healthy aging profile of octogenarians can be explained by age group, marital status, and the presence of a caregiver.

Download Full-text

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2017224118 ◽

2020 ◽

Vol 118 (1) ◽

pp. e2017224118

Author(s):

Adolfo G. Cuevas ◽

Frank D. Mann ◽

David R. Williams ◽

Robert F. Krueger

Keyword(s):

Negative Affect ◽

Principal Components ◽

The United States ◽

European Ancestry ◽

Prevention Measures ◽

Latent Factor ◽

Genetic Liability ◽

Polygenic Scores ◽

Anxiety Depression ◽

The Impact

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 (β = 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.

Download Full-text

Do psychiatric diseases follow annual cyclic seasonality?

PLoS Biology ◽

10.1371/journal.pbio.3001347 ◽

2021 ◽

Vol 19 (7) ◽

pp. e3001347

Author(s):

Hanxin Zhang ◽

Atif Khan ◽

Qi Chen ◽

Henrik Larsson ◽

Andrey Rzhetsky

Keyword(s):

Infectious Diseases ◽

Psychiatric Disorders ◽

Seasonal Affective Disorder ◽

Age Groups ◽

The United States ◽

Time Interval ◽

Health Seeking ◽

Swedish Population ◽

Annual Cycles ◽

Very Large Datasets

Seasonal affective disorder (SAD) famously follows annual cycles, with incidence elevation in the fall and spring. Should some version of cyclic annual pattern be expected from other psychiatric disorders? Would annual cycles be similar for distinct psychiatric conditions? This study probes these questions using 2 very large datasets describing the health histories of 150 million unique U.S. citizens and the entire Swedish population. We performed 2 types of analysis, using “uncorrected” and “corrected” observations. The former analysis focused on counts of daily patient visits associated with each disease. The latter analysis instead looked at the proportion of disease-specific visits within the total volume of visits for a time interval. In the uncorrected analysis, we found that psychiatric disorders’ annual patterns were remarkably similar across the studied diseases in both countries, with the magnitude of annual variation significantly higher in Sweden than in the United States for psychiatric, but not infectious diseases. In the corrected analysis, only 1 group of patients—11 to 20 years old—reproduced all regularities we observed for psychiatric disorders in the uncorrected analysis; the annual healthcare-seeking visit patterns associated with other age-groups changed drastically. Analogous analyses over infectious diseases were less divergent over these 2 types of computation. Comparing these 2 sets of results in the context of published psychiatric disorder seasonality studies, we tend to believe that our uncorrected results are more likely to capture the real trends, while the corrected results perhaps reflect mostly artifacts determined by dominantly fluctuating, health-seeking visits across a given year. However, the divergent results are ultimately inconclusive; thus, we present both sets of results unredacted, and, in the spirit of full disclosure, leave the verdict to the reader.

Download Full-text