The stimulating effect of bright light on physical performance depends on internal time.

The human circadian clock regulates the daily timing of sleep, alertness and performance and is synchronized to the 24-h day by the environmental light-dark cycle. Bright light exposure has been shown to positively affect sleepiness and alertness, yet little is known about its effects on physical performance, especially in relation to chronotype. We, therefore, exposed 43 male participants (mean age 24.5 yrs ± SD 2.3 yrs) in a randomized crossover study to 160 minutes of bright (BL: ≈ 4.420 lx) and dim light (DL: ≈ 230 lx). During the last 40 minutes of these exposures, participants performed a bicycle ergometer test. Time-of-day of the exercise sessions did not differ between the BL and DL condition. Chronotype (MSF(sc), mid-sleep time on free days corrected for oversleep due to sleep debt on workdays) was assessed by the Munich ChronoType Questionnaire (MCTQ). Total work was significantly higher in BL (median 548.4 kJ, min 411.82 kJ, max 875.20 kJ) than in DL (median 521.5 kJ, min 384.33 kJ, max 861.23 kJ) (p = 0.004) going along with increased exhaustion levels in BL (blood lactate (+12.7%, p = 0.009), heart rate (+1.8%, p = 0.031), and Borg scale ratings (+2.6%, p = 0.005)) in all participants. The differences between total work levels in BL and DL were significantly higher (p = 0.004) if participants were tested at a respectively later time point after their individual mid-sleep (chronotype). These novel results demonstrate, that timed BL exposure enhances physical performance with concomitant increase in individual strain, and is related not only to local (external) time, but also to an individual's internal time

Steigende Energiepreise: Ein Vorschlag für eine ökologisch und sozial treffsichere Maßnahme

Der Krieg in der Ukraine trifft über mehrere Wirkungskanäle die heimische Volkswirtschaft. So belasten stark gestiegene Energie- und Rohstoffpreise Haushalte und Unternehmen. Das Energiekosten-Entlastungspaket der Bundesregierung setzt Maßnahmen zur Abfederung dieser Belastungen. Mit diesem Policy Brief möchten wir einen konstruktiven Beitrag zur Debatte leisten und schlagen eine wirtschaftspolitische Maßnahme vor, die ökologisch und sozial treffsicher erscheint: eine Transferzahlung, die umgekehrt proportional zur motobezogenen Versicherungssteuer ausbezahlt wird

Humor in radiological breast cancer screening: a way of improving patient service?

BACKGROUND Breast cancer screening is essential in detecting breast tumors, however, the examination is stressful. In this study we analyzed whether humor enhances patient satisfaction. METHODS In this prospective randomized study 226 patients undergoing routine breast cancer screening at a single center during October 2020 to July 2021 were included. One hundred thirty-two were eligible for the study. Group 1 (66 patients) received an examination with humorous intervention, group 2 (66 patients) had a standard breast examination. In the humor group, the regular business card was replaced by a self-painted, humorous business card, which was handed to the patient at the beginning of the examination. Afterwards, patients were interviewed with a standardized questionnaire. Scores between the two study groups were compared with the Mann-Whitney U test or Fisher's exact test. P-values were adjusted with the Holm's method. Two-sided p-values < 0.05 were considered significant. RESULTS One hundred thirty-two patients, 131 female and 1 male, (mean age 59 ± 10.6 years) remained in the final study cohort. Patients in the humor group remembered the radiologist's name better (85%/30%, P < .001), appreciated the final discussion with the radiologist more (4.67 ± 0.73-5;[5, 5] vs. 4.24 ± 1.1-5;[4, 5], P = .017), felt the radiologist was more empathetic (4.94 ± 0.24-5;[5, 5] vs.4.59 ± 0.64-5;[4, 5], P < .001), and rated him as a humorous doctor (4.91 ± 0.29-5;[5, 5] vs. 2.26 ± 1.43-1;[1, 4], P < .001). Additionally, patients in the humor group tended to experience less anxiety (p = 0.166) and felt the doctor was more competent (p = 0.094). CONCLUSION Humor during routine breast examinations may improve patient-radiologist relationship because the radiologist is considered more empathetic and competent, patients recall the radiologist's name more easily, and value the final discussion more. TRIAL REGISTRATION We have a general approval from our ethics committee because it is a retrospective survey, the patient lists for the doctors were anonymized and it is a qualitative study, since the clinical processes are part of the daily routine examinations and are used independently of the study. The patients have given their consent to this study and survey

Association of polygenic score for major depression with response to lithium in patients with bipolar disorder

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in patients with BD. Weighted polygenic scores (PGSs) were computed for major depression (MD) at different GWAS p value thresholds using genetic data obtained from 2586 bipolar patients who received lithium treatment and took part in the Consortium on Lithium Genetics (ConLi+Gen) study. Summary statistics from genome-wide association studies in MD (135,458 cases and 344,901 controls) from the Psychiatric Genomics Consortium (PGC) were used for PGS weighting. Response to lithium treatment was defined by continuous scores and categorical outcome (responders versus non-responders) using measurements on the Alda scale. Associations between PGSs of MD and lithium treatment response were assessed using a linear and binary logistic regression modeling for the continuous and categorical outcomes, respectively. The analysis was performed for the entire cohort, and for European and Asian sub-samples. The PGSs for MD were significantly associated with lithium treatment response in multi-ethnic, European or Asian populations, at various p value thresholds. Bipolar patients with a low polygenic load for MD were more likely to respond well to lithium, compared to those patients with high polygenic load [lowest vs highest PGS quartiles, multi-ethnic sample: OR = 1.54 (95% CI: 1.18–2.01) and European sample: OR = 1.75 (95% CI: 1.30–2.36)]. While our analysis in the Asian sample found equivalent effect size in the same direction: OR = 1.71 (95% CI: 0.61–4.90), this was not statistically significant. Using PGS decile comparison, we found a similar trend of association between a high genetic loading for MD and lower response to lithium. Our findings underscore the genetic contribution to lithium response in BD and support the emerging concept of a lithium-responsive biotype in BD

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Genetic Overlap Between Alzheimer’s Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Background: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. Methods: We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Results: Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the MARK2 gene (lead SNP rs10792421, conjunctional FDR=0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR=0.022, opposite direction of effect). Conclusions: We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP

Bipolar multiplex families have an increased burden of common risk variants for psychiatric disorders.

Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 individuals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development

Genome-wide association study identifies 74 loci associated with educational attainment

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases

The genetics of the mood disorder spectrum:genome-wide association analyses of over 185,000 cases and 439,000 controls

Background Mood disorders (including major depressive disorder and bipolar disorder) affect 10-20% of the population. They range from brief, mild episodes to severe, incapacitating conditions that markedly impact lives. Despite their diagnostic distinction, multiple approaches have shown considerable sharing of risk factors across the mood disorders. Methods To clarify their shared molecular genetic basis, and to highlight disorder-specific associations, we meta-analysed data from the latest Psychiatric Genomics Consortium (PGC) genome-wide association studies of major depression (including data from 23andMe) and bipolar disorder, and an additional major depressive disorder cohort from UK Biobank (total: 185,285 cases, 439,741 controls; non-overlapping N = 609,424). Results Seventy-three loci reached genome-wide significance in the meta-analysis, including 15 that are novel for mood disorders. More genome-wide significant loci from the PGC analysis of major depression than bipolar disorder reached genome-wide significance. Genetic correlations revealed that type 2 bipolar disorder correlates strongly with recurrent and single episode major depressive disorder. Systems biology analyses highlight both similarities and differences between the mood disorders, particularly in the mouse brain cell-types implicated by the expression patterns of associated genes. The mood disorders also differ in their genetic correlation with educational attainment – positive in bipolar disorder but negative in major depressive disorder. Conclusions The mood disorders share several genetic associations, and can be combined effectively to increase variant discovery. However, we demonstrate several differences between these disorders. Analysing subtypes of major depressive disorder and bipolar disorder provides evidence for a genetic mood disorders spectrum