Incidence and outcome of acquired demyelinating syndromes in Dutch children: update of a nationwide and prospective study

Introduction: Acquired demyelinating syndromes (ADS) are immune-mediated demyelinating disorders of the central nervous system in children. A nationwide, multicentre and prospective cohort study was initiated in the Netherlands in 2006, with a reported ADS incidence of 0.66/100,000 per year and MS incidence of 0.15/100,000 per year in the period between 2007 and 2010. In this study, we provide an update on the incidence and the long-term follow-up of ADS in the Netherlands. Methods: Children < 18 years with a first attack of demyelination were included consecutively from January 2006 to December 2016. Diagnoses were based on the International Paediatric MS study group consensus criteria. Outcome data were collected by neurological and neuropsychological assessments, and telephone call assessments. Results: Between 2011 and 2016, 55/165 of the ADS patients were diagnosed with MS (33%). This resulted in an increased ADS and MS incidence of 0.80/100,000 per year and 0.26/100,000 per year, respectively. Since 2006 a total of 243 ADS patients have been included. During follow-up (median 55 months, IQR 28–84), 137 patients were diagnosed with monophasic disease (56%), 89 with MS (37%) and 17 with multiphasic disease other than MS (7%). At least one form of residual deficit including cognitive impairment was observed in 69% of all ADS patients, even in monophasic ADS. An Expanded Disability Status Scale score of ≥ 5.5 was reached in 3/89 MS patients (3%). Conclusion: The reported incidence of ADS in Dutch children has increased since 2010. Residual deficits are common in this group, even in monophasic patients. Therefore, long-term follow-up in ADS patients is warranted

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Elevated CRP levels are associated with increased carotid atherosclerosis independent of visceral obesity

Visceral obesity (VO) is associated with an increased risk of cardiovascular disease. Elevated C-reactive protein (CRP) levels are associated with VO and cardiovascular disease. After exploring the relation between CRP and VO, we aimed to evaluate the VO independent relation between CRP and carotid atherosclerosis. The prevalence of inflammation was evaluated in 439 male subjects with VO without type 2 diabetes and manifest cardiovascular disease. Waist circumference significantly correlated with CRP (r: 0.20, p 118 cm had low CRP levels. From the 439 subjects, 40 subjects were prospectively selected for MRI assessment of carotid atherosclerosis and visceral and subcutaneous adipose tissue distribution in a case-control setting matching for age and waist circumference. Twenty male subjects with age >50 years with CRP levels >2.5mg/L (CRP+) were compared to 20 controls with CRP levels <1.8 mg/L (CRP-). Maximum vessel wall thickness in CRP+ was significantly higher both in the common carotid artery (15%, p <0.01) and the bulb region (18%, p <0.01). The distribution of fat in visceral and subcutaneous deposits was not significantly different between CRP+ and CRP-. Elevated CRP levels are associated with significantly increased maximum vessel wall thickness independent of VO and of MRI measured adipose tissue distribution, both in the common carotid artery and the carotid bul

Associations between sociodemographic, sampling and health factors and various salivary cortisol indicators in a large sample without psychopathology

Background: Cortisol levels are increasingly often assessed in large-scale psychosomatic research. Although determinants of different salivary cortisol indicators have been described, they have not yet been systematically studied within the same study with a Large sample size. Sociodemographic, health and sampling-related determinants of salivary cortisol Levels were examined in a sample without potential disturbances because of psychopathology. Methods: Using 491 respondents (mean age = 43.0 years, 59.5% female) without lifetime psychiatric disorders from the Netherlands Study of Depression and Anxiety (NESDA), sociodemographic, sampling and health determinants of salivary cortisol levels were examined. Respondents collected seven salivary cortisol samples providing information about 1-h awakening cortisol, diurnal slope, evening cortisol and a dexamethasone (0.5 mg) suppression test (DST). Results: Higher overall morning cortisol values were found for smokers, physically active persons, persons without cardiovascular disease, sampling on a working day or in a month with less daylight. In addition, the cortisol awakening response was significantly flattened for mates, persons with cardiovascular disease, those with late awakening times and those with longer sleep duration. Diurnal slope was steeper in men, physically active persons, late awakeners, working persons, and season with less daylight. A higher evening cortisol level was associated with older age, smoking and season with more daylight. Cortisol suppression after dexamethasone ingestion was found to be less pronounced in smokers, less active persons and sampling on a weekday. Conclusion: Sociodemographic variables (sex, age), sampling factors (awakening time, working day, sampling month, steep duration) and health indicators (smoking, physical activity, cardiovascular disease) were shown to influence different features of salivary cortisol levels. Smoking had the most consistent effect on all cortisol variables. These factors should be considered in psychoneuroendocrinology research. (C) 2009 Elsevier Ltd. All rights reserved

Major Depressive Disorder and Hypothalamic-Pituitary-Adrenal Axis Activity Results From a Large Cohort Study

Context: There is a central belief that depression is associated with hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in higher cortisol levels. However, results are inconsistent. Objective: To examine whether there is an association between depression and various cortisol indicators in a large cohort study. Design, Setting, and Participants: Data are from 1588 participants of the Netherlands Study of Depression and Anxiety who were recruited from the community, general practice care, and specialized mental health care. Three groups were compared: 308 control subjects without psychiatric disorders, 579 persons with remitted (no current) major depressive disorder (MDD), and 701 persons with a current MDD diagnosis, as assessed using the DSM-IV Composite International Diagnostic Interview. Main Outcome Measures: Cortisol levels were measured in 7 saliva samples to determine the 1-hour cortisol awakening response, evening cortisol levels, and cortisol suppression after a 0.5-mg dexamethasone suppression test. Results: Both the remitted and current MDD groups showed a significantly higher cortisol awakening response compared with control subjects (effect size [Cohen d] range, 0.15-0.25). Evening cortisol levels were higher among the current MDD group at 10 PM but not at 11 PM. The postdexamethasone cortisol level did not differ between the MDD groups. Most depression characteristics (severity, chronicity, symptom profile, prior childhood trauma) were not associated with hypothalamic-pituitary-adrenal axis activity except for comorbid anxiety, which tended to be associated with a higher cortisol awakening response. The use of psychoactive medication was generally associated with lower cortisol levels and less cortisol suppression after dexamethasone ingestion. Conclusions: This large cohort study shows significant, although modest, associations between MDD and specific hypothalamic-pituitary-adrenal axis indicators. Because a higher cortisol awakening response was observed among both subjects with current MDD and subjects with remitted MDD, this may be indicative of an increased biological vulnerability for depression

Networking by small-molecules hormones in plant immunity.

Abstract: Plants live in complex environments in which they intimately interact with a broad range of microbial pathogens and insect herbivores with different lifestyles and infection or feeding strategies. The evolutionary arms race between plants and their attackers provided plants with a sophisticated defense system that, like the animal innate immune system, recognizes the attacker and responds by activating specific defenses that are specifically directed against the invader. Recent advances in plant immunity research provided exciting new insights into the underlying defense signaling network. Diverse small-molecule hormones play pivotal roles in the regulation of this network. Their signaling pathways cross-communicate in an antagonistic or synergistic manner, providing the plant with a powerful capacity to finely tailor its immune response to the attacker encountered. Pathogens and insects, on the other hand, can manipulate the plant&apos;s defense signaling network for their own benefit by affecting phytohormone homeostasis to antagonize the host immune response

Oxytocin and vasopressin in male forensic psychiatric patients with personality disorders and healthy controls

Oxytocin and vasopressin are neuropeptides implicated as modulators of human aggressive behavior. In animal models, administration of oxytocin generally attenuates aggressive behavior, but in humans the effects of oxytocin appear to be more nuanced. Vasopressin seems to have an opposing influence on aggression in animal studies, but much less research has been done in humans. We performed a cross-sectional study in which we measured oxytocin and vasopressin levels in forensic psychiatric male patients with a personality disorder (N = 38) and healthy male controls (N = 108). Elevated salivary oxytocin (B = −0.10, P = 0.02) and reduced urinary vasopressin (B = 0,19, P < 0.01) levels were found in patients compared to controls. Within the patient group urinary oxytocin levels were positively associated with psychopathy scores as measured with the PCL-R (B = 0.02, P = 0.02). These findings suggest that baseline levels in forensic psychiatric patients diagnosed with a primary personality disorder might be counterintuitive, as oxytocin levels are higher than expected and vasopressin levels are lower than those of healthy controls. More generally, the results imply a complex role of these neuropeptides on human behavior, in line with the social salience theory