Levels and determinants of inflammatory biomarkers in a Swiss population-based sample (CoLaus study)

Objective to assess the levels and determinants of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) in a healthy Caucasian population. Methods population sample of 2884 men and 3201 women aged 35 to 75. IL-1β, IL-6 and TNF-α were assessed by a multiplexed particle-based flow cytometric assay and CRP by an immunometric assay. Results Spearman rank correlations between duplicate cytokine measurements (N = 80) ranged between 0.89 and 0.96; intra-class correlation coefficients ranged between 0.94 and 0.97, indicating good reproducibility. Among the 6085 participants, 2289 (37.6%), 451 (7.4%) and 43 (0.7%) had IL-1β, IL-6 and TNF-α levels below detection limits, respectively. Median (interquartile range) for participants with detectable values were 1.17 (0.48–3.90) pg/ml for IL-1β; 1.47 (0.71–3.53) pg/ml for IL-6; 2.89 (1.82–4.53) pg/ml for TNF-α and 1.3 (0.6–2.7) ng/ml for CRP. On multivariate analysis, greater age was the only factor inversely associated with IL-1β levels. Male sex, increased BMI and smoking were associated with greater IL-6 levels, while no relationship was found for age and leisure-time PA. Male sex, greater age, increased BMI and current smoking were associated with greater TNF-α levels, while no relationship was found with leisure-time PA. CRP levels were positively related to age, BMI and smoking, and inversely to male sex and physical activity. Conclusion Population-based levels of several cytokines were established. Increased age and BMI, and to a lesser degree sex and smoking, significantly and differentially impact cytokine levels, while leisure-time physical activity has little effect.

What percentage of people in the general population satisfies the current clinical at-risk criteria of psychosis?

The clinical validity of at-risk criteria of psychosis had been questioned based on epidemiological studies that have reported much higher prevalence and annual incidence rates of psychotic-like experiences (PLEs as assessed by either self rating questionnaires or layperson interviews) in the general population than of the clinical phenotype of psychotic disorders (van Os et al., 2009). Thus, it is unclear whether “current at-risk criteria reflect behaviors so common among adolescents and young adults that a valid distinction between ill and non-ill persons is difficult” (Carpenter, 2009). We therefore assessed the 3-month prevalence of at-risk criteria by means of telephone interviews in a randomly drawn general population sample from the at-risk age segment (age 16–35 years) in the Canton Bern, Switzerland. Eighty-five of 102 subjects had valid phone numbers, 21 of these subjects refused (although 6 of them signaled willingness to participate at a later time), 4 could not be contacted. Sixty subjects (71% of the enrollment fraction) participated. Two participants met exclusion criteria (one for being psychotic, one for lack of language skills). Twenty-two at-risk symptoms were assessed for their prevalence and severity within the 3 months prior to the interview by trained clinical raters using (i) the Structured Interview for Prodromal Syndromes (SIPS; Miller et al., 2002) for the evaluation of 5 attenuated psychotic and 3 brief limited intermittent psychotic symptoms (APS, BLIPS) as well as state-trait criteria of the ultra-high-risk (UHR) criteria and (ii) the Schizophrenia Proneness Instrument, Adult version (SPI-A; Schultze-Lutter et al., 2007) for the evaluation of the 14 basic symptoms included in COPER and COGDIS (Schultze-Lutter et al., 2008). Further, psychiatric axis I diagnoses were assessed by means of the Mini-International Neuropsychiatric Interview, M.I.N.I. (Sheehan et al., 1998), and psychosocial functioning by the Scale of Occupational and Functional Assessment (SOFAS; APA, 1994). All interviewees felt ‘rather’ or ‘very’ comfortable with the interview. Of the 58 included subjects, only 1 (2%) fulfilled APS criteria by reporting the attenuated, non-delusional idea of his mind being literally read by others at a frequency of 2–3 times a week that had newly occurred 6 weeks ago. BLIPS, COPER, COGDIS or state-trait UHR criteria were not reported. Yet, twelve subjects (21%) described sub-threshold at-risk symptoms: 7 (12%) reported APS relevant symptoms but did not meet time/frequency criteria of APS, and 9 (16%) reported COPER and/or COGDIS relevant basic symptoms but at an insufficient frequency or as a trait lacking increase in severity; 4 of these 12 subjects reported both sub-threshold APS and sub-threshold basic symptoms. Table 1 displays type and frequency of the sub-threshold at-risk symptoms.

Basic symptoms in the general population and in psychotic and non-psychotic psychiatric adolescents

Cognitive-perceptive 'basic symptoms' are used complementary to ultra-high-risk criteria in order to predict onset of psychosis in the pre-psychotic phase. The aim was to investigate the prevalence of a broad selection of 'basic symptoms' in a representative general adolescent population sample (GPS; N=96) and to compare it with adolescents first admitted for early onset psychosis (EOP; N=87) or non-psychotic psychiatric disorders (NP; N=137).

Evidence for chronic low-grade systemic inflammation in individuals with agoraphobia from a population-based prospective study.

BACKGROUND Anxiety disorders have been linked to an increased risk of incident coronary heart disease in which inflammation plays a key pathogenic role. To date, no studies have looked at the association between proinflammatory markers and agoraphobia. METHODS In a random Swiss population sample of 2890 persons (35-67 years, 53% women), we diagnosed a total of 124 individuals (4.3%) with agoraphobia using a validated semi-structured psychiatric interview. We also assessed socioeconomic status, traditional cardiovascular risk factors (i.e., body mass index, hypertension, blood glucose levels, total cholesterol/high-density lipoprotein-cholesterol ratio), and health behaviors (i.e., smoking, alcohol consumption, and physical activity), and other major psychiatric diseases (other anxiety disorders, major depressive disorder, drug dependence) which were treated as covariates in linear regression models. Circulating levels of inflammatory markers, statistically controlled for the baseline demographic and health-related measures, were determined at a mean follow-up of 5.5 ± 0.4 years (range 4.7 - 8.5). RESULTS Individuals with agoraphobia had significantly higher follow-up levels of C-reactive protein (p = 0.007) and tumor-necrosis-factor-α (p = 0.042) as well as lower levels of the cardioprotective marker adiponectin (p = 0.032) than their non-agoraphobic counterparts. Follow-up levels of interleukin (IL)-1β and IL-6 did not significantly differ between the two groups. CONCLUSIONS Our results suggest an increase in chronic low-grade inflammation in agoraphobia over time. Such a mechanism might link agoraphobia with an increased risk of atherosclerosis and coronary heart disease, and needs to be tested in longitudinal studies.

Frequency of and predictors for patient-reported medical and medication errors in Switzerland

OBJECTIVES: To analyse the frequency of and identify risk factors for patient-reported medical errors in Switzerland. The joint effect of risk factors on error-reporting probability was modelled for hypothetical patients. METHODS: A representative population sample of Swiss citizens (n = 1306) was surveyed as part of the Commonwealth Fund’s 2010 lnternational Survey of the General Public’s Views of their Health Care System’s Performance in Eleven Countries. Data on personal background, utilisation of health care, coordination of care problems and reported errors were assessed. Logistic regression analysis was conducted to identify risk factors for patients’ reports of medical mistakes and medication errors. RESULTS: 11.4% of participants reported at least one error in their care in the previous two years (8% medical errors, 5.3% medication errors). Poor coordination of care experiences was frequent. 7.8% experienced that test results or medical records were not available, 17.2% received conflicting information from care providers and 11.5% reported that tests were ordered although they had been done before. Age (OR = 0.98, p = 0.014), poor health (OR = 2.95, p = 0.007), utilisation of emergency care (OR = 2.45, p = 0.003), inpatient-stay (OR = 2.31, p = 0.010) and poor care coordination (OR = 5.43, p <0.001) are important predictors for reporting error. For high utilisers of care that unify multiple risk factors the probability that errors are reported rises up to p = 0.8. CONCLUSIONS: Patient safety remains a major challenge for the Swiss health care system. Despite the health related and economic burden associated with it, the widespread experience of medical error in some subpopulations also has the potential to erode trust in the health care system as a whole.

Effect of short-wave (6-22 MHz) magnetic fields on sleep quality and melatonin cycle in humans: the Schwarzenburg shut-down study

This paper describes the results of a unique "natural experiment" of the operation and cessation of a broadcast transmitter with its short-wave electromagnetic fields (6-22 MHz) on sleep quality and melatonin cycle in a general human population sample. In 1998, 54 volunteers (21 men, 33 women) were followed for 1 week each before and after shut-down of the short-wave radio transmitter at Schwarzenburg (Switzerland). Salivary melatonin was sampled five times a day and total daily excretion and acrophase were estimated using complex cosinor analysis. Sleep quality was recorded daily using a visual analogue scale. Before shut down, self-rated sleep quality was reduced by 3.9 units (95% CI: 1.7-6.0) per mA/m increase in magnetic field exposure. The corresponding decrease in melatonin excretion was 10% (95% CI: -32 to 20%). After shutdown, sleep quality improved by 1.7 units (95% CI: 0.1-3.4) per mA/m decrease in magnetic field exposure. Melatonin excretion increased by 15% (95% CI: -3 to 36%) compared to baseline values suggesting a rebound effect. Stratified analyses showed an exposure effect on melatonin excretion in poor sleepers (26% increase; 95% CI: 8-47%) but not in good sleepers. Change in sleep quality and melatonin excretion was related to the extent of magnetic field reduction after the transmitter's shut down in poor but not good sleepers. However, blinding of exposure was not possible in this observational study and this may have affected the outcome measurements in a direct or indirect (psychological) way.

Parental understanding of wheeze and its impact on asthma prevalence estimates

The epidemiology of wheeze in children, when assessed by questionnaires, is dependent on parents' understanding of the term "wheeze". In a questionnaire survey of a random population sample of 4,236 children aged 6-10 yrs, parents' definition of wheeze was assessed. Predictors of a correct definition were determined and the potential impact of incorrect answers on prevalence estimates from the survey was assessed. Current wheeze was reported by 13.2% of children. Overall, 83.5% of parents correctly identified "whistling or squeaking" as the definition of wheeze; the proportion was higher for parents reporting wheezy children (90.4%). Frequent attacks of reported wheeze (adjusted odds ratio (OR) 3.0), maternal history of asthma (OR 1.5) and maternal education (OR 1.5) were significantly associated with a correct answer, while the converse was found for South Asian ethnicity (OR 0.6), first language not English (OR 0.6) and living in a deprived neighbourhood (OR 0.6). In summary, the present study showed that misunderstanding could lead to an important bias in assessing the prevalence of wheeze, resulting in an underestimation in children from South Asian and deprived family backgrounds. Prevalence estimates for the most severe categories of wheeze might be less affected by this bias and questionnaire surveys on wheeze should incorporate measures of parents' understanding of the term wheeze.

Health-related quality of life in rural children living in four European countries: the GABRIEL study

OBJECTIVE Measuring children's health-related quality of life (HRQOL) is of growing importance given increasing chronic diseases. By integrating HRQOL questions into the European GABRIEL study, we assessed differences in HRQOL between rural farm and non-farm children from Germany, Austria, Switzerland and Poland to relate it to common childhood health problems and to compare it to a representative, mostly urban German population sample (KIGGS). METHODS The parents of 10,400 school-aged children answered comprehensive questionnaires including health-related questions and the KINDL-R questions assessing HRQOL. RESULTS Austrian children reported highest KINDL-R scores (mean: 80.9; 95 % CI [80.4, 81.4]) and Polish children the lowest (74.5; [73.9, 75.0]). Farm children reported higher KINDL-R scores than non-farm children (p = 0.002). Significantly lower scores were observed in children with allergic diseases (p < 0.001), with sleeping difficulties (p < 0.001) and in overweight children (p = 0.04). The German GABRIEL sample reported higher mean scores (age 7-10 years: 80.1, [79.9, 80.4]; age 11-13 years: 77.1, [74.9, 79.2]) compared to the urban KIGGS study (age 7-10 years: 79.0, [78.7-79.3]; age 11-13 years: 75.1 [74.6-75.6]). Socio-demographic or health-related factors could not explain differences in HRQOL between countries. CONCLUSIONS Future increases in chronic diseases may negatively impact children's HRQOL.

WHEN DOES THE TROUBLE START? OBESITY, DIABETES RISKS AND METABOLIC DISTURBANCES IN YOUNG PEOPLE WITH PSYCHOSIS

People with psychotic disorders have higher mortality rates compared to the general population. Most deaths are due to cardiovascular (CV) disease, reflecting high rates of CV risk factors such as obesity and diabetes. Treatment with antipsychotic drugs is associated with weight gain in clinical trials. However, there is little information about how these drugs affect children and young people, and how early in the course of treatment the elevation in CV risk factors begins. This information is essential in understanding the costs and benefits of these treatments in young people, and establishing preventive and early intervention services to address physical health comorbidities. This symposium reports both prospective and naturalistic data from children and adolescents treated with antipsychotic drugs. These studies demonstrate that adverse effects on cardiometabolic measures, notably BMI and insulin resistance, become apparent very soon after treatment is initiated. Further, children and adolescents appear to be even more sensitive to these effects than adults. Population-wide studies are also informative. Danish data showing that young people exposed to antipsychotics have a higher risk of diabetes, compared with young people who had a psychiatric diagnosis but were not exposed to antipsychotic drugs, will be presented. In addition, an Australian comparison between a large, nationally representative sample of people with psychosis and a general population sample shows that higher rates of obesity and other cardiometabolic abnormalities are already evident in people with psychosis by the age of 25 years. Young people living with psychosis are already disadvantaged by the demands of living with mental illness, stigma, and social factors such as unemployment and low income. The addition of obesity, diabetes and other comorbidities adds a further burden. The data presented highlights the need for careful selection of antipsychotic drugs, regular monitoring of physical health and early intervention when weight gain, glucose dysregulation, or other cardiometabolic abnormalities are detected.

General distress, hopelessness—suicidal ideation and worrying in adolescence: Concurrent and predictive validity of a symptom-level bifactor model for clinical diagnoses

BACKGROUND: Clinical disorders often share common symptoms and aetiological factors. Bifactor models acknowledge the role of an underlying general distress component and more specific sub-domains of psychopathology which specify the unique components of disorders over and above a general factor. METHODS: A bifactor model jointly calibrated data on subjective distress from The Mood and Feelings Questionnaire and the Revised Children's Manifest Anxiety Scale. The bifactor model encompassed a general distress factor, and specific factors for (a) hopelessness-suicidal ideation, (b) generalised worrying and (c) restlessness-fatigue at age 14 which were related to lifetime clinical diagnoses established by interviews at ages 14 (concurrent validity) and current diagnoses at 17 years (predictive validity) in a British population sample of 1159 adolescents. RESULTS: Diagnostic interviews confirmed the validity of a symptom-level bifactor model. The underlying general distress factor was a powerful but non-specific predictor of affective, anxiety and behaviour disorders. The specific factors for hopelessness-suicidal ideation and generalised worrying contributed to predictive specificity. Hopelessness-suicidal ideation predicted concurrent and future affective disorder; generalised worrying predicted concurrent and future anxiety, specifically concurrent generalised anxiety disorders. Generalised worrying was negatively associated with behaviour disorders. LIMITATIONS: The analyses of gender differences and the prediction of specific disorders was limited due to a low frequency of disorders other than depression. CONCLUSIONS: The bifactor model was able to differentiate concurrent and predict future clinical diagnoses. This can inform the development of targeted as well as non-specific interventions for prevention and treatment of different disorders.

More adaptive versus less maladaptive coping: What is more predictive of symptom severity? Development of a new scale to investigate coping profiles across different psychopathological syndromes

BACKGROUND: Lack of adaptive and enhanced maladaptive coping with stress and negative emotions are implicated in many psychopathological disorders. We describe the development of a new scale to investigate the relative contribution of different coping styles to psychopathology in a large population sample. We hypothesized that the magnitude of the supposed positive correlation between maladaptive coping and psychopathology would be stronger than the supposed negative correlation between adaptive coping and psychopathology. We also examined whether distinct coping style patterns emerge for different psychopathological syndromes. METHODS: A total of 2200 individuals from the general population participated in an online survey. The Patient Health Questionnaire-9 (PHQ-9), the Obsessive-Compulsive Inventory revised (OCI-R) and the Paranoia Checklist were administered along with a novel instrument called Maladaptive and Adaptive Coping Styles (MAX) questionnaire. Participants were reassessed six months later. RESULTS: MAX consists of three dimensions representing adaptive coping, maladaptive coping and avoidance. Across all psychopathological syndromes, similar response patterns emerged. Maladaptive coping was more strongly related to psychopathology than adaptive coping both cross-sectionally and longitudinally. The overall number of coping styles adopted by an individual predicted greater psychopathology. Mediation analysis suggests that a mild positive relationship between adaptive and certain maladaptive styles (emotional suppression) partially accounts for the attenuated relationship between adaptive coping and depressive symptoms. LIMITATIONS: Results should be replicated in a clinical population. CONCLUSIONS: Results suggest that maladaptive and adaptive coping styles are not reciprocal. Reducing maladaptive coping seems to be more important for outcome than enhancing adaptive coping. The study supports transdiagnostic approaches advocating that maladaptive coping is a common factor across different psychopathologies.

Associations between alcohol consumption and selected cytokines in a Swiss population-based sample (CoLaus study)

To assess the associations between alcohol consumption and cytokine levels (interleukin-1beta - IL-1β; interleukin-6 - IL-6 and tumor necrosis factor-α - TNF-α) in a Caucasian population.

Association between circulating cytokine levels, diabetes and insulin resistance in a population-based sample (CoLaus study)

OBJECTIVE: The associations between inflammation, diabetes and insulin resistance remain controversial. Hence, we assessed the associations between diabetes, insulin resistance (using HOMA-IR) and metabolic syndrome with the inflammatory markers high sensitivity C-reactive protein (hs-CRP), interleukin-1beta (IL-1β), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α). DESIGN: CROSS-SECTIONAL STUDY: PARTICIPANTS: 2884 MEN AND 3201 WOMEN AGED 35 TO 75: METHODS: CRP was assessed by immunoassay and cytokines by multiplexed flow cytometric assay. In a subgroup of 532 participants an oral glucose tolerance test was performed to screen for impaired glucose tolerance (IGT). RESULTS: IL-6, TNF-α and hs-CRP were significantly and positively correlated with fasting plasma glucose, insulin and HOMA-IR. Participants with diabetes had higher IL-6, TNF-α and hs-CRP levels than participants without diabetes; this difference persisted for hs-CRP after multivariate adjustment. Participants with metabolic syndrome had increased IL-6, TNF-α and hs-CRP levels; these differences persisted after multivariate adjustment. Participants in the highest quartile of HOMA-IR had increased IL-6, TNF-α and hs-CRP levels; these differences persisted for TNF-α and hs-CRP after multivariate adjustment. No association was found between IL-1β levels and all diabetes and insulin resistance markers studied. Finally, participants with IGT had higher hs-CRP levels than participants with a normal OGTT, but this difference disappeared after controlling for body mass index (BMI). CONCLUSION: subjects with diabetes, metabolic syndrome and increased insulin resistance present with increased levels of IL6, TNF-α and hs-CRP, while no association was found with IL-1β. The increased inflammatory state of subjects with IGT is partially explained by increased BMI. © 2012 Blackwell Publishing Ltd.