Robert Szulkin

The epidemiology of heart failure, based on data for 2.1 million inhabitants in Sweden.

The epidemiology of congestive heart failure (CHF) is likely to have changed due to changes in demography, risk factors, diagnostic procedures, and medical care. Prevailing information is in part old, incomplete, and to some extent contradictory. We determined the current prevalence, incidence, mortality, and 5‐year survival rate of CHF, and possible temporal changes in Sweden.

A prostate cancer susceptibility allele at 6q22 increases RFX6 expression by modulating HOXB13 chromatin binding

Genome-wide association studies have identified thousands of SNPs associated with predisposition to various diseases, including prostate cancer. However, the mechanistic roles of these SNPs remain poorly defined, particularly for noncoding polymorphisms. Here we find that the prostate cancer risk-associated SNP rs339331 at 6q22 lies within a functional HOXB13-binding site. The risk-associated T allele at rs339331 increases binding of HOXB13 to a transcriptional enhancer, conferring allele-specific upregulation of the rs339331-associated gene RFX6. Suppression of RFX6 diminishes prostate cancer cell proliferation, migration and invasion. Clinical data indicate that RFX6 upregulation in human prostate cancers correlates with tumor progression, metastasis and risk of biochemical relapse. Finally, we observe a significant association between the risk-associated T allele at rs339331 and increased RFX6 mRNA levels in human prostate tumors. Together, our results suggest that rs339331 affects prostate cancer risk by altering RFX6 expression through a functional interaction with the prostate cancer susceptibility gene HOXB13.

Differences in neighborhood accessibility to health-related resources: A nationwide comparison between deprived and affluent neighborhoods in Sweden

This nationwide Swedish study used geocoded data from all businesses in Sweden to examine the distribution of 12 main categories of goods, services, and resources in 6986 neighborhoods, categorized as low, moderate, and high neighborhood deprivation. The main findings were that high- and moderate-deprivation neighborhoods had a significantly higher prevalence of all types of goods, services, and resources than low-deprivation neighborhoods. These findings do not support previous research that hypothesizes that poorer health among people in deprived neighborhoods is explained by a lack of health-promoting resources, although a higher presence of health-damaging resources may play a role.

Inflammation and positive affect are associated with subjective health in women of the general population

Poor subjective health has been associated with higher levels of inflammatory cytokines. We investigated whether such an association would apply to women of the general population. Levels of cytokines, affect and subjective health were assessed in 347 women of the general population aged 45 to 90 years. Higher levels of interleukin-6 were associated with poor subjective health, especially in participants over 65 years of age. Positive affect was a more robust determinant of subjective health than negative affect. The presence of low-grade inflammation and absence of positive affect, rather than presence of negative affect, may be important determinants of subjective health.

Prediction of individual genetic risk to prostate cancer using a polygenic score.

Polygenic risk scores comprising established susceptibility variants have shown to be informative classifiers for several complex diseases including prostate cancer. For prostate cancer it is unknown if inclusion of genetic markers that have so far not been associated with prostate cancer risk at a genome‐wide significant level will improve disease prediction.

Genome-Wide Association Study of Prostate Cancer–Specific Survival

Background: Unnecessary intervention and overtreatment of indolent disease are common challenges in clinical management of prostate cancer. Improved tools to distinguish lethal from indolent disease are critical. Methods: We performed a genome-wide survival analysis of cause-specific death in 24,023 prostate cancer patients (3,513 disease-specific deaths) from the PRACTICAL and BPC3 consortia. Top findings were assessed for replication in a Norwegian cohort (CONOR). Results: We observed no significant association between genetic variants and prostate cancer survival. Conclusions: Common genetic variants with large impact on prostate cancer survival were not observed in this study. Impact: Future studies should be designed for identification of rare variants with large effect sizes or common variants with small effect sizes. Cancer Epidemiol Biomarkers Prev; 24(11); 1796–800. ©2015 AACR.

Prostate cancer risk variants are not associated with disease progression

Currently used prognostic markers are limited in their ability to accurately predict disease progression among patients with localized prostate cancer. We examined 23 reported prostate cancer susceptibility variants for association with disease progression.

High lifelong relapse rate of psychiatric disorders among women with postpartum psychosis

Abstract Background: The relapse rate for psychiatric disorders after postpartum psychosis is high. Apart from subsequent puerperal periods, previous studies have not examined when relapses in psychiatric disorders occur. In addition, little is known about the impact of certain individual factors on the risk of non-puerperal readmission among women with previous postpartum psychosis. Aims: The first aim was to examine the association between non-puerperal readmission due to psychiatric disorders and years of follow-up (in total, 30 years) in women with postpartum psychosis. The second aim was to examine the impact of age, type of psychosis, previous hospitalization for psychiatric disorders and level of education on the risk of non-puerperal readmission due to psychiatric disorders. Methods: All Swedish women aged 20–44 with postpartum psychosis (n =3140) were followed between 1975 and 2004 for non-puerperal readmission due to psychiatric disorders. A Cox frailty regression model was used to estimate hazard ratios for non-puerperal readmission. Results: The risk of non-puerperal readmission, although gradually decreasing with time, remained high many years after the postpartum psychosis. The risk of non-puerperal readmission was significantly higher among women with schizophrenia, lower levels of education and previous psychiatric hospitalization. Conclusions: Postpartum psychosis is often part of a lifelong recurrent psychiatric disorder. Women with schizophrenia, lower levels of education and hospitalization due to a psychiatric disorder prior to postpartum psychosis have a higher risk of non-puerperal readmission. Clinical implications: The findings constitute important knowledge for all healthcare workers encountering women with a previous postpartum psychosis.

Associations Between Leptin and Self-Rated Health in Men and Women

BACKGROUND As an important mediator by which the brain receives information about the bodys energy state, leptin may be associated with subjectively perceived health. OBJECTIVE The main aim of the present study was to investigate concurrent and prospective associations between leptin and self-rated health (SRH), a strong predictor of morbidity and mortality, in a random population sample. An additional aim was to examine whether sick leave was associated with leptin and poor SRH. METHODS In a prospective, population-based cohort study in Sweden, men and women underwent a medical examination in 1998, at which time blood was drawn and participants were asked to respond to a questionnaire concerning demographics, health behavior, and psychosocial factors. In 2000, the participants responded to a second questionnaire sent by postal mail. Spearman rank correlations were used to investigate the relationships between leptin, SRH, sick leave, and background variables. Partial Spearman coefficients were then calculated to investigate the patterns of association between leptin, SRH, and sick leave independent of age, body mass index (BMI), presence of diagnosis, and testosterone or estradiol. RESULTS A total of 98 men and 104 women, aged 23 to 76 years, and 91 men and 96 women at follow-up, participated in the study. In men, relatively higher levels of leptin were prospectively associated with relatively worse SRH (rho = 0.20; P = 0.05), but the relationship was not significant in the cross-sectional analysis (rho = 0.18; P = 0.07). This association was not found in women. When controlling for age, BMI, presence of diagnosis, and testosterone, higher levels of leptin were associated with poor SRH in men in cross-sectional analysis (rho = 0.27; P < 0.01) but not prospectively. In women, leptin was not associated with SRH in cross-sectional analysis, but relatively higher levels were prospectively associated with better SRH when adjusted for background factors and estradiol (rho = -0.26; P < 0.05). SRH was independently associated with future sick leave in both men (rho = 0.34; P < 0.01) and women (rho = 0.30; P < 0.05), whereas no association between leptin and future sick leave was found. CONCLUSIONS Contrasting associations were found between men and women in the relationship between leptin and SRH. Based on the finding that higher leptin levels were associated with better SRH in women than in men, along with corroboration from recent studies, we propose that leptin may serve different psychobiological functions in men than in women.

Possible Biomarkers of Chronic Stress Induced Exhaustion - A Longitudinal Study.

Background Vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and monocyte chemotactic protein-1 (MCP-1) have previously been suggested to be potential biomarkers for chronic stress induced exhaustion. The knowledge about VEGF has increased during the last decades and supports the contention that VEGF plays an important role in stress and depression. There is scarce knowledge on the possible relationship of EGF and MCP-1 in chronic stress and depression. This study further examines the role of VEGF, EGF and MCP-1 in women with chronic stress induced exhaustion and healthy women during a follow-up period of two years. Methods and Findings Blood samples were collected from 105 women with chronic stress induced exhaustion on at least 50% sick leave for at least three months, at inclusion (T0), after 12 months (T12) and after 24 months (T24). Blood samples were collected at inclusion (T0) in 116 physically and psychiatrically healthy women. The plasma levels of VEGF, EGF and MCP-1 were analyzed using Biochip Array Technology. Women with chronic stress induced exhaustion had significantly higher plasma levels of VEGF and EGF compared to healthy women at baseline, T12 and at T24. There was no significant difference in plasma levels of MCP-1. Plasma levels of VEGF and EGF decreased significantly in women with chronic stress induced exhaustion during the two years follow-up. Conclusions The replicated findings of elevated levels of VEGF and EGF in women with chronic stress induced exhaustion and decreasing plasma levels of VEGF and EGF during the two years follow-up add important knowledge to the pathophysiology of chronic stress induced exhaustion.