"The Heidelberg Five" personality dimensions: Genome-wide associations, polygenic risk for neuroticism, and psychopathology 20 years after assessment.

HeiDE is a longitudinal population-based study that started in the 1990s and, at baseline, assessed an array of health-related personality questionnaires in 5133 individuals. Five latent personality dimensions (The Heidelberg Five) were identified and interpreted as Emotional Lability (ELAB), Lack of Behavioral Control (LBCN), Type A Behavior (TYAB), Locus of Control over Disease (LOCC), and Psychoticism (PSYC). At follow-up, 3268 HeiDE participants (post-QC) were genotyped on single nucleotide polymorphism (SNP) arrays. To further characterize The Heidelberg Five, we analyzed genomic underpinnings, their relations to the genetic basis of the Big Five trait Neuroticism, and longitudinal associations with psychiatric symptoms at follow-up. SNP-based heritability was significant for ELAB (34%) and LBCN (29%). A genome-wide association study for each personality dimension was conducted; only the phenotype PSYC yielded a genome-wide significant finding (p < 5 × 10-8 , top SNP rs138223660). Gene-based analyses identified significant findings for ELAB, TYAB, and PSYC. Polygenic risk scores for Neuroticism were only associated with ELAB. Each of The Heidelberg Five was related to depressive symptoms at follow-up. ELAB, LBCN, and PSYC were also associated with lifetime anxiety symptoms. These results highlight the clinical importance of health-related personality traits and identify LBCN as a heritable "executive function" personality trait.

Interplay between the genetics of personality traits, severe psychiatric disorders and COVID-19 host genetics in the susceptibility to SARS-CoV-2 infection.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, with its impact on our way of life, is affecting our experiences and mental health. Notably, individuals with mental disorders have been reported to have a higher risk of contracting SARS-CoV-2. Personality traits could represent an important determinant of preventative health behaviour and, therefore, the risk of contracting the virus. AIMS: We examined overlapping genetic underpinnings between major psychiatric disorders, personality traits and susceptibility to SARS-CoV-2 infection. METHOD: Linkage disequilibrium score regression was used to explore the genetic correlations of coronavirus disease 2019 (COVID-19) susceptibility with psychiatric disorders and personality traits based on data from the largest available respective genome-wide association studies (GWAS). In two cohorts (the PsyCourse (n = 1346) and the HeiDE (n = 3266) study), polygenic risk scores were used to analyse if a genetic association between, psychiatric disorders, personality traits and COVID-19 susceptibility exists in individual-level data. RESULTS: We observed no significant genetic correlations of COVID-19 susceptibility with psychiatric disorders. For personality traits, there was a significant genetic correlation for COVID-19 susceptibility with extraversion (P = 1.47 × 10-5; genetic correlation 0.284). Yet, this was not reflected in individual-level data from the PsyCourse and HeiDE studies. CONCLUSIONS: We identified no significant correlation between genetic risk factors for severe psychiatric disorders and genetic risk for COVID-19 susceptibility. Among the personality traits, extraversion showed evidence for a positive genetic association with COVID-19 susceptibility, in one but not in another setting. Overall, these findings highlight a complex contribution of genetic and non-genetic components in the interaction between COVID-19 susceptibility and personality traits or mental disorders.

Nocturnal sleep duration and cognitive impairment in a population-based study of older adults.

OBJECTIVE: We aimed to investigate the association between nocturnal sleep duration, changes in nocturnal sleep duration and cognitive impairment in older adults. METHODS: 4010 participants of a population-based cohort study provided information on nocturnal sleep duration at baseline (1991-1995) and at follow-up (2002/2003). 792 follow-up participants aged 70+ by 2006 participated in telephone-based cognitive assessments. Several cognitive tests were used including the telephone interview for cognitive status (TICS). Cognitive impairment was defined as <31 points on the TICS (13.0%) and as below this percentile on the other tests. Based on individual tests, a verbal memory score and a total score were constructed. Multivariable prevalence ratios (PRs) of cognitive impairment and 95% confidence intervals (95%CIs) were computed using Poisson regression. Analyses were restricted to those free of depression in 2002/2003 (n = 695). RESULTS: Sleeping or=9 h was positively, although imprecisely, associated with impairment of verbal memory (PR = 1.7, 95%CI = 1.0, 3.0), and less pronounced with the other cognitive measures. An increase in sleep duration from 7-8 h in 1992-1995 to >or=9 h 8.5 years later (versus sleeping 7-8 h at both time points) was associated with an increased prevalence of cognitive impairment according to the TICS (PR = 2.1, 95% = 1.0, 4.5) and the verbal memory score (PR = 2.0, 95%CI = 1.0, 3.8). CONCLUSIONS: Increases in sleep duration are associated with cognitive impairment. A biological explanation for this association is currently lacking. Increases in sleep duration could be a marker of cognitive deficits.

Obesity and adult asthma: potential effect modification by gender, but not by hay fever.

PURPOSE: First, we sought to estimate the magnitude of the cross-sectional associations between overweight/obesity and asthma stratified by gender and by self-reported hay fever and second we sought to assess both directions of causality in longitudinal analyses. METHODS: We used cross-sectional and longitudinal data from a population-based cohort study (n=5114, ages 40-65 at baseline). After 8.5 years, 4010 adults were followed-up by questionnaires. Self-reported height and weight were used to calculate body mass index categories. Multivariate adjusted prevalence ratios (PRs), relative risks (RRs), and 95% confidence intervals (95% CI) were calculated using Poisson regression. RESULTS: In cross-sectional analyses, adjusted PRs were comparable for overweight women and men but differed between obese women and men (PR 1.93, 95% CI 1.19-3.14 and PR 0.98, 95% CI 0.56-1.72). PRs were similar when stratified by hay fever. Longitudinal analyses suggested that overweight/obesity did not increase asthma risk substantially (RR 1.02, 95% CI 0.50-2.06), but a relation between asthma and subsequent weight gain could not be excluded (RR 1.34, 95% CI 1.01-1.77). CONCLUSIONS: The prevalence of asthma is almost twice as high in obese versus normal weight women, but not in obese men. The association between overweight/obesity and asthma does not vary by hay fever. A causal relationship between asthma and incident weight gain cannot be excluded.

The role of the TPH1 and TPH2 genes for nicotine dependence: a genetic association study in two different age cohorts.

Based on pharmacological and genetic studies suggesting a role of the serotonergic system for nicotine dependence, two genetic variants, one on the tryptophan hydroxylase 1 (TPH1) and one on the TPH2 gene, were investigated. The TPH2 -703G/T promoter polymorphism was associated with smoking status and age of smoking onset in two independent Caucasian samples of different age cohorts. Sample 1 consisted of 3,602 subjects of a population-based cohort study of whom 95% were 40-65 years old, and sample 2 consisted of 723 subjects in the twenties. The TPH1 779A/C was only investigated in sample 2 where additional data with respect to the degree of nicotine dependence were assessed. Results yield support for previous findings of an association between the AA genotype of TPH1 779A/C and nicotine status and a tendency for a heterosis effect with respect to the degree of nicotine dependence. The TPH2 -703G/T was significantly associated with age of smoking onset in both samples. The interaction between the T allele and gender was significant in both samples. Carriers of the GG genotype started significantly earlier to smoke than carriers with a T allele. In the older cohort, age of onset was earlier in carriers of the GG genotype only in men, and in the younger cohort the GG genotype predisposes only women to start smoking earlier in life. This interaction could constitute a gene-by-environment interaction that is discussed on the background of previous studies relating the -703G/T polymorphism to anxiety, a personality dimension that has been shown to be a risk factor for nicotine dependence.

Diabetes and cognitive function in a population-based study of elderly women and men.

OBJECTIVES: The aim of this study was to examine the association between diabetes and cognitive function in the elderly. RESEARCH DESIGN AND METHODS: From January to December 2003, all 740 participants, aged 70 years or more, of an ongoing population-based cohort study were eligible for a telephone interview on cognitive function. Cognitive function was assessed using validated instruments, including the Telephone Interview of Cognitive Status (TICS) and the East Boston Memory Test (EBMT). Information on diabetes was available from prior questionnaires and was validated in 2002. We used multivariable logistic regression to estimate odds ratios (OR) of an impaired cognitive function (below 25th percentile) and their 95% confidence intervals (CI) adjusting for age, gender, smoking, alcohol consumption, body mass index (BMI), physical exercise, educational level, and depressive symptoms. RESULTS: Out of 473 participants interviewed (64.9%), 66 had diabetes (14.1%). The adjusted OR for diabetes and impaired cognitive function assessed by TICS was 2.3 (95% CI: 1.2-4.3). Diabetes was also associated with performance on delayed recall EBMT (adjusted OR=2.0; 95% CI: 1.0-4.1), but not immediate EBMT recall (adjusted OR=1.0; 95% CI: 0.5-2.1). The association between diabetes and cognitive function was a bit more pronounced in participants in whom diabetes was diagnosed 12 (median) or more years prior (adjusted OR with TICS=2.4; 95% CI: 1.0-5.8) and in those without antidiabetic treatment (age- and sex-adjusted OR=3.4; 95% CI: 1.7-6.5). CONCLUSION: Diabetes should be considered to be a risk factor for cognitive impairment in the elderly, which might be attenuated by antidiabetic treatment.

A longitudinal study of quality of life in patients with chronic heart failure following an exercise training program.

BACKGROUND: Chronic heart failure (CHF) will become one of the greatest medical challenges during the next decades. This is especially true with regard to elderly patients. Besides medical diagnostics and drug therapy, efficient treatment of CHF must also include exercise training. AIMS: The purpose of our study was 1) to record health-related quality of life (QOL) in elderly patients with CHF and 2) to assess the efficacy of a training program, as well as to evaluate any changes detected during a six month follow-up. METHODS: In our non-randomized study, 116 patients, divided according to age into Group 1 (>70 years) and Group 2 (<70 years), took part in a 4-week training program. RESULTS: There were differences in the clinical parameters and the QOL between the older and the younger patients both after 4 weeks and at the follow-up. After six months, however, the older patients again recorded having an inferior QOL to that of the younger patients. CONCLUSION: Elderly patients can also benefit from physical exercise training, with improvement in clinical parameters and QOL. In order to maintain the subjectively improved QOL in the long term, however, continued special heart failure education and support is required.

Personality, lifestyle, and risk of cardiovascular disease and cancer: follow-up of population based cohort.

OBJECTIVE: To study the relation between measures of personality and risk of cardiovascular disease and cancer in a large cohort. DESIGN: Follow-up of population based cohort. SETTING: Heidelberg, Germany. PARTICIPANTS: 5114 women and men aged 40-65 in 1992-5. MAIN OUTCOME MEASURES: Psychological traits assessed by several standardised personality questionnaires in 1992-5, related to cause of death (to 2002-3) or reported incidence of cardiovascular diseases and cancer (validated by treating doctors). Relative risks (and 95% confidence intervals) for combined morbidity and mortality according to five important personality traits were estimated using multivariable Cox proportional hazards models. RESULTS: During median follow-up of 8.5 years, 257 participants died and 72 were diagnosed with a heart attack, 62 with stroke, and 240 with cancer (morbidity and mortality combined). A high internal locus of control over disease was associated with a decreased risk of myocardial infarction (adjusted relative risk for an increase of 1 SD = 0.75; 95% confidence interval 0.58 to 0.96). An increase of 1 SD in time urgency was associated with a decreased risk of cancer (adjusted relative risk 0.83; 0.73 to 0.95). Other major personality traits--anger control, psychoticism, and symptoms of depression--were not consistently associated with myocardial infarction, stroke, or cancer. CONCLUSION: Internal locus of control over disease and time urgency seem to be associated with reduced risk for common chronic diseases, probably by affecting unmeasured health related behaviour. The other personality traits assessed had no major impact on cardiovascular disease and cancer.