Positive association between social capital and the quality of health care service: A cross-sectional study.

BACKGROUND: Social capital is an acknowledged theoretical concept in work environment research focusing on collective resources that arise from social networks between employees in the workplace. Social capital is divided into bonding (in the work unit), bridging (between work units), and linking social capital (between the work units and management). However, only a few studies have investigated the relationship between social capital and the quality of health care, which is the key outcome of hospital services. OBJECTIVE: We investigated the associations between bonding, bridging and two types of linking social capital with the self-reported quality of health care services among Danish hospital employees. Next, we directly compared how social capital, workload and work pace each affected the quality of health care. DESIGN: A cross-sectional study at Regional Hospital West Jutland, Denmark. DATA: Questionnaire data were collected from 1589 Danish hospital employees. We used validated scales for social capital, workload, and work pace and self-developed scales for clinical quality, quality of patient involvement, and overall professional quality. METHODS: Binary logistic regression analyses were conducted. RESULTS: The analyses showed significant, positive associations of bonding and bridging social capital with all types of quality and negative associations between workload and all types of quality. The work pace was negatively associated with clinical quality. When covariates were included in the model, the associations remained statistically significant and showed no decrease in odds ratios. The marginal effects showed that when bonding and bridging social capital were increased by a single scale point, the predicted probability for a high clinical quality increased by an average of 0.5 percentage points. This increase corresponds to a change in the predicted probability of self-reported high clinical quality from 10% for the lowest reported bridging social capital to 54% for the highest reported bridging social capital. For workload and work pace, the effects were -0.2 and -0.3 percentage points, respectively. DISCUSSION & CONCLUSIONS: This study adds to the literature on positive work environment factors by focusing on social capital and the importance of well-functioning relationships within and especially between hospital units for high-quality health care. Hence, bridging and bonding social capital should be included in theoretical frameworks, as well as in hospital strategies and work environment guidelines to potentially improve the quality of health care services. However, further studies are needed to develop and test the effects of specific social capital interventions on the quality of health care services.

Comparison of the clinical presentation across two waves of COVID-19: a retrospective cohort study.

BACKGROUND: Only a few studies have performed comprehensive comparisons between hospitalized patients from different waves of COVID-19. Thus, we aimed to compare the clinical characteristics and laboratory data of patients admitted to the western part of Denmark during the first and second waves of COVID-19 in 2020. Furthermore, we aimed to identify risk factors for critical COVID-19 disease and to describe the available information on the sources of infection. METHODS: We performed a retrospective study of medical records from 311 consecutive hospitalized patients, 157 patients from wave 1 and 154 patients from wave 2. The period from March 7 to June 30, 2020, was considered wave 1, and the period from July 1st to December 31, 2020, was considered wave 2. Data are presented as the total study population, as a comparison between waves 1 and 2, and as a comparison between patients with and without critical COVID-19 disease (nonsurvivors and patients admitted to the intensive care unit (ICU)). RESULTS: Patients admitted during the first COVID-19 wave experienced a more severe course of disease than patients admitted during wave 2. Admissions to the ICU and fatal disease were significantly higher among patients admitted during wave 1 compared to wave 2. The percentage of patients infected at hospital decreased in wave 2 compared to wave 1, whereas more patients were infected at home during wave 2. We found no significant differences in sociodemographics, lifestyle information, or laboratory data in the comparison of patients from waves 1 and 2. However, age, sex, smoking status, comorbidities, fever, and dyspnea were identified as risk factors for critical COVID-19 disease. Furthermore, we observed significantly increased levels of C-reactive protein and creatinine, and lower hemoglobin levels among patients with critical disease. CONCLUSIONS: At admission, patients were more severely ill during wave 1 than during wave 2, and the outcomes were worse during wave 1. We confirmed previously identified risk factors for critical COVID-19 disease. In addition, we found that most COVID-19 infections were acquired at home.

Predictors for wellbeing and characteristics of mental health after stroke.

BACKGROUND: Poor mental health after stroke is common and complex. We aimed to identify predictors of poor wellbeing and to examine the overlap of poor wellbeing, fatigue, and depression. METHOD: Consecutive first-ever ischemic stroke-patients filled in questionnaires on wellbeing, fatigue, and depression at baseline and at one and six months. The World Health Organization 5-Item Wellbeing-Index (WHO-5), the Major Depression Inventory, and the Multidimensional Fatigue Inventory were used. Patients were genotyped according to serotonin-transporter gene polymorphisms. Multivariable logistic regression was used to identify potential predictors of poor wellbeing (WHO-5 score <50). Overlap between wellbeing, fatigue, and depression was examined using an Euler diagram. RESULTS: We included 919 patients. The prevalence of poor wellbeing was 279 (30.4%) six months after stroke. Living alone at stroke onset was the strongest predictor of poor wellbeing with a mutually adjusted odds ratio of 1.53 (95% confidence interval (CI): 1.03 to 2.28) at one month and 1.77 (CI: 1.13 to 2.76) at six months. Severe stroke at admission also predicted poor wellbeing at six months. Abnormal fatigue occurred in half and incorporated almost all patients with poor wellbeing. Less than 5% fulfilled the criteria for depression at any point and almost all of these patients had poor wellbeing and abnormal fatigue. Antidepressants were used by 292 (31.8%) during follow-up. LIMITATIONS: Cognitive impairment was not measured and could interact with wellbeing post-stroke. CONCLUSION: Living alone strongly predicted poor wellbeing after stroke. Satisfactory mental health-recovery seems to require psychosocial interventions when indicated in combination with antidepressant treatment.

Serotonergic Regulation and Cognition after Stroke: The Role of Antidepressant Treatment and Genetic Variation.

INTRODUCTION: Serotonin affects several brain functions including cognition. The serotonin transporter (SERT) regulates brain serotonin levels through reuptake into neurons. The gene encoding this transporter, the SERT gene, has several functional polymorphisms affecting the number of transporters and thereby the serotonin levels. SERT gene expression may be important for cognition and selective serotonin reuptake inhibitors (SSRI) may improve cognition post stroke. We therefore examined the association between SERT genotypes, cognitive function and early treatment with the SSRI citalopram among non-depressed Caucasian stroke patients. PATIENTS AND METHODS: SERT gene polymorphisms in 270 non-depressed first-ever acute ischemic stroke patients randomized to citalopram, n = 130, or placebo, n = 140, were investigated. Patients were genotyped for a length polymorphism (L = long and S = short allele) and a single nucleotide polymorphism (A/G substitution) dividing the L-allele into LA and LG. According to these genotypes, patients were further grouped according to low (S/S, LG/S and LG/LG), medium (S/LA and LG/LA), or high functional gene expression (LALA). Cognition was measured by the Symbol Digit Modalities Test (SDMT) at 1 and 6 months. Mean SDMT scores according to genotype and randomization groups were compared using multiple logistic regression adjusting for age, stroke severity, premorbid functional status, and vascular risk factors including smoking, hypertension, and diabetes. RESULTS: Stratified by genotype groups, there were no statistically significant differences in SDMT scores between randomization groups. Placebo-treated patients with low SERT expression genotypes, however, tended to have lower mean SDMT scores (at 1 month: 30.2, SD 10.8) compared to citalopram-treated patients (33.6, SD 13.7). Within the placebo group, the low genotype expression patients had significantly lower adjusted mean SDMT scores at 1 month compared to the high genotype expression patients (adjusted mean difference of -6 points, CI -12.0 to -0.05). We found similar results at 6 months, although not statistically significant. The genotype expression was not associated with SDMT scores among citalopram-treated patients. CONCLUSION: There was no difference in cognition between citalopram and placebo-treated patients according to the genotype group. Our results indicate, however, that low expression SERT genotype may contribute to reduced cognitive function post stroke as placebo-treated patients with low SERT expression tended to score lower on the SDMT. The significant difference in SDMT scores between low and high expression patients was present only in the placebo-treated group, thereby warranting further exploration of the potential effect of early citalopram treatment on cognitive functioning. Our results are preliminary and need replication in larger-scale studies.

Latent toxoplasmosis and psychiatric symptoms - A role of tryptophan metabolism?

Toxoplasma gondii (TOX) is a common parasite which infects approximately one third of the human population. In recent years, it has been suggested that latent toxoplasmosis may be a risk factor for the development of mental disorders, particularly schizophrenia and anxiety. With regards to depression the results have been varied. The main objective of this study was to examine subpopulations from the Danish PRISME and GENDEP populations for TOX IgG antibodies. These consisted of: a group with symptoms of anxiety, a group suffering from burnout syndrome, as well as two different subpopulations with depression of differing severity. The secondary objective of this study was to examine whether tryptophan metabolism was altered in TOX-positive subjects within each subpopulation. Our results show that the anxiety and burnout populations were more likely to be TOX IgG seropositive. Furthermore, we find that the moderate-severe but not mild-moderate depressive subpopulation were associated with TOX seropositivety, suggesting a possible role of symptom severity. Additionally, we found that TOX positive subjects in the anxiety and burnout subpopulations had altered tryptophan metabolism. This relationship did not exist in the mild-moderate depressive subpopulation. These results suggest that TOX seropositivity may be related to anxiety, burnout and potentially to severity of depression. We furthermore show that the psychiatric symptoms could be associated with an altered tryptophan metabolism.

Investigation of serum levels of sortilin in response to antidepressant treatment.

BACKGROUND: The identification of biomarkers for depression is of great clinical relevance as the diagnosis is currently subjective. Recent research points towards sortilin as a potential biomarker for depression, and the aim of the current study was to investigate the serum sortilin level in response to antidepressant treatment. METHODS: The study included 56 depressed individuals of which 41 responded to treatment. Depression scores and serum levels of sortilin were measured at baseline and after 12 weeks of antidepressant treatment. Statistical analyses were performed using Stata 13. RESULTS: The depression score and response to treatment were not predicted by the sortilin level. Likewise, we observed no significant change in serum sortilin levels following 12 weeks of antidepressant treatment. Furthermore, no association between the serum sortilin level and depression score was observed. CONCLUSION: The results do not point towards sortilin as a state-dependent biomarker.

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.

BACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease. RESULTS: We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. CONCLUSIONS: We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.

DNA Methylation at the Neonatal State and at the Time of Diagnosis: Preliminary Support for an Association with the Estrogen Receptor 1, Gamma-Aminobutyric Acid B Receptor 1, and Myelin Oligodendrocyte Glycoprotein in Female Adolescent Patients with OCD.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder. Non-genetic factors and their interaction with genes have attracted increasing attention. Epigenetics is regarded an important interface between environmental signals and activation/repression of genomic responses. Epigenetic mechanisms have not previously been examined in OCD in children and adolescents. The aim of the present study was to examine the DNA methylation profile of selected genes in blood spots from neonates later diagnosed with OCD and in the same children/adolescents at the time of diagnosis compared with age- and sex-matched controls. Furthermore, we wanted to characterize the association of the differential methylation profiles with the severity of OCD and treatment outcome. Dried and new blood spot samples were obtained from 21 female children/adolescents with verified OCD and 12 female controls. The differential methylation was analyzed using a linear model and the correlation with the severity of OCD and treatment outcome was analyzed using the Pearson correlation. We evaluated selected Illumina Infinium HumanMethylation450 BeadChip probes within and up to 100,000 bp up- and downstream of 14 genes previously associated with OCD (SLC1A1, SLC25A12, GABBR1, GAD1, DLGAP1, MOG, BDNF, OLIG2, NTRK2 and 3, ESR1, SL6A4, TPH2, and COMT). The study found no significantly differential methylation. However, preliminary support for a difference was found for the gamma-aminobutyric acid (GABA) B receptor 1 (cg10234998, cg17099072) in blood samples at birth and for the estrogen receptor 1 (ESR1) (cg10939667), the myelin oligodendrocyte glycoprotein (MOG) (cg16650906), and the brain-derived neurotrophic factor (BDNF) (cg14080521) in blood samples at the time of diagnosis. Preliminary support for an association was observed between the methylation profiles of GABBR1 and MOG and baseline severity, treatment effect, and responder status; and between the methylation profile of ESR1 and baseline severity. To our knowledge, this is the first study to examine the DNA methylation profiles in OCD. The study points towards possible differences in the methylation profiles and suggests a correlation with the severity of OCD. However, the results warrant further studies in larger sample sets.

Salivary cortisol and depression in public sector employees: cross-sectional and short term follow-up findings.

INTRODUCTION: Increased cortisol levels have been suggested to play a role in the development of depression. An association has been shown in some studies but not consistently. The timing of an association is uncertain, and long-term follow-up studies may miss associations in narrower time windows. In the present study, we examined the association of several cortisol measures and depression in a repeated cross-sectional and short-term follow-up design. Depression was assessed by both self-reported symptoms of depression and clinical interviews. METHOD: In 2007, 10,036 public sector employees received a questionnaire along with salivary cortisol test tubes for home administration. Morning (30min after awakening) and evening (2000h) salivary samples were collected. Questionnaires and valid saliva samples were returned from 3536 employees. Approximately 3.6 months later a subsample of the participants collected three morning saliva samples (at awakening, 20min and 40min after awakening) plus an evening sample (2000h); participants with high baseline scores of self-reported depressive symptoms, burnout and perceived stress were invited to a standardized interview (SCAN) to detect clinical depression; and the symptom questionnaire was repeated for subsample participants. The study was repeated in 2009 with questionnaires and salivary test tubes (n=2408). In four cross-sectional and two short-term follow-up analyses odds ratios of depressive symptoms and of clinical depression were estimated by logistic regression for morning, evening, mean and the difference between morning and evening cortisol (slope). For the subsample, awakening response (CAR) and area under the curve (AUC) cortisol measures were calculated. We adjusted for sex, age, income, education, family history of depression, physical activity and alcohol consumption. RESULTS: None except one of the measures of salivary cortisol were associated with self-reported depressive symptoms or clinical depression, neither in the four cross-sectional analyses nor in the two short term follow-up analyses. E.g. in 2007, the adjusted odds ratios (OR) of depressive symptoms by a one unit increase in morning and evening cortisol (ln(nmol/litre saliva)) were 1.01 (95% CI: 0.88-1.17) and 1.05 (0.93-1.18), respectively. The one exception was significant at p=0.04 and was considered as due to chance. CONCLUSION: In this large study, salivary cortisol was not associated with self-reported symptoms of depression or with clinical depression.

A two-year follow-up study of salivary cortisol concentration and the risk of depression.

Stress is a suspected cause of depression. High cortisol concentration, a biomarker of an activated stress response, has been found in depressed patients. The aim of this study was to determine if a high level of salivary cortisol is a risk factor of depression. In 2007, we enrolled 4467 public employees. Morning and evening salivary cortisol concentration were measured for each participant. Participants reporting high levels of depressive, burnout, or stress symptoms, assessed by questionnaires were assigned to a psychiatric interview. In this interview 98 participants were diagnosed with depression and subsequently excluded. Two years later in 2009, 2920 participants who had provided at least one valid saliva cortisol measurement at baseline participated at follow up. The psychiatric interviews were repeated and 62 cases of newly onset depression were diagnosed. Odds ratios of depression were estimated for every 1.0nmol/l increase in morning, evening, and daily mean cortisol concentration, as well as for the difference between morning and evening cortisol concentration. The risk of depression decreased by increasing daily mean cortisol concentration and by increasing difference between morning and evening concentrations, while morning and evening cortisol concentrations were not significantly associated with depression. The adjusted odds ratios for 1.0nmol/l increase in morning, evening, and daily mean cortisol concentration were 0.69 (95% CI: 0.45, 1.05), 0.87 (95% CI: 0.59, 1.28), and 0.53 (95% CI: 0.32, 0.90), respectively. The adjusted odds ratio for 1.0nmol/l increase in difference between morning and evening concentration were 0.64 (95% CI: 0.45, 0.90). This study did not support the hypothesis that high salivary cortisol concentration is a risk factor of depression, but indicate that low mean salivary cortisol concentration and a small difference between morning and evening cortisol concentration may be risk factors of depression.

Support for a bipolar affective disorder susceptibility locus on chromosome 12q24.3.

OBJECTIVE: Linkage and association studies of bipolar affective disorder (BAD) point out chromosome 12q24 as a region of interest. METHODS: To investigate this region further, we conducted an association study of 22 DNA markers within a 1.14 Mb region in a Danish sample of 166 patients with BAD and 311 control individuals. Two-hundred and four Danish patients with schizophrenia were also included in the study. RESULTS: We observed highly significant allelic and genotypic association between BAD and two highly correlated markers. The risk allele of both markers considered separately conferred an odds ratio of 2 to an individual carrying one risk allele and an odds ratio of 4 for individuals carrying both risk alleles assuming an additive genetic model. These findings were supported by the haplotype analysis. In addition, we obtained a replication of four markers associated with BAD in an earlier UK study. The most significantly associated marker was also analyzed in a Scottish case-control sample and was earlier associated with BAD in the UK cohort. The association of that particular marker was strongly associated with BAD in a meta-analysis of the Danish, Scottish and UK sample (P=0.0003). The chromosome region confined by our most distant markers is gene-poor and harbours only a few predicted genes. This study implicates the Slynar locus. We confirmed one annotated Slynar transcript and identified a novel transcript in human brain cDNA. CONCLUSION: This study confirms 12q24.3 as a region of functional importance in the pathogenesis of BAD and highlights the importance of focused genotyping.

A population-based association study of glutamate decarboxylase 1 as a candidate gene for autism.

Linkage studies, genome-wide scans and screening of possible candidate genes suggest that chromosome 2q31 may harbour one or more susceptibility genes for autism. The glutamate decarboxylase gene 1 (GAD1) located within chromosome 2q31 encodes the enzyme, GAD67, catalyzing the production of gamma-aminobutyric acid (GABA) from glutamate. Numerous independent findings have suggested the GABAergic system to be involved in autism. The present study investigates a Danish population-based, case-control sample of 444 subjects with childhood autism and 444 controls. Nine single nucleotide polymorphisms (SNPs) comprising the GAD1 gene and the microsatellite marker D2S2381 were examined for association with autism. We found no association between childhood autism and any single marker or 2-5 marker haplotypes. However, a rare nine-marker haplotype was associated with childhood autism. We cannot exclude neither GAD1 as a susceptibility gene nor the possibility of another susceptibility gene for autism to be located on chromosome 2q31.