Scientists discover robust evidence that chronic fatigue syndrome is a biological illness

"Researchers at the Center for Infection and Immunity at Columbia University's Mailman School of Public Health identified distinct immune changes in patients diagnosed with chronic fatigue syndrome, known medically as myalgic encephalomyelitis (ME/CFS) or systemic exertion intolerance disease. The findings could help improve diagnosis and identify treatment options for the disabling disorder, in which symptoms range from extreme fatigue and difficulty concentrating to headaches and muscle pain."



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A study relates the level of pollutants accumulated in the body with obesity levels

"This research has analysed the levels of pollutants accumulated in adipose tissue (fat) in nearly 300 men and women, who were attended in the surgery services of two hospitals in the province of Granada (Spain).
The substances, known as persistent organic pollutants (POPs), can remain in the environment for years, even decades, without degrading.
"Humans are exposed to POPs mainly through diet. POPs accumulate gradually in body fat, and this is the reason why the median levels in our study give us an idea of an individual's accumulated exposition over a number of years," says Juan Pedro Arrebola, the main author of the article.
Using complex statistical methods, these scientists confirmed that the accumulated levels of several POPs were related to obesity and to serum levels of cholesterol and triglycerides in individuals, irrespective of the gender, age, place of residence or smoking habits of participants in the survey."


Mining for viral fragments in methylation enriched sequencing data.

Most next generation sequencing experiments generate more data than is usable for the experimental set up. For example, methyl-CpG binding domain (MBD) affinity purification based sequencing is often used for DNA-methylation profiling, but up to 30% of the sequenced fragments cannot be mapped uniquely to the reference genome. Here we present and evaluate a methodology for the identification of viruses in these otherwise unused paired-end MBD-seq data. Viral detection is accomplished by mapping non-reference alignable reads to a comprehensive set of viral genomes. As viruses play an important role in epigenetics and cancer development, 92 (pre)malignant and benign samples, originating from two different collections of cervical samples and related cell lines, were used in this study. These samples include primary carcinomas (n = 22), low- and high-grade cervical intraepithelial neoplasia (CIN1 and CIN2/3 - n = 2/n = 30) and normal tissue (n = 20), as well as control samples (n = 17). Viruses that were detected include phages, adenoviruses, herpesviridae and HPV. HPV, which causes virtually all cervical cancers, was identified in 95% of the carcinomas, 100% of the CIN2/3 samples, both CIN1 samples and in 55% of the normal samples. Comparing the amount of mapped fragments on HPV for each HPV-infected sample yielded a significant difference between normal samples and carcinomas or CIN2/3 samples (adjusted p-values resp. <10(-5), <10(-5)), reflecting different viral loads and/or methylation degrees in non-normal samples. Fragments originating from different HPV types could be distinguished and were independently validated by PCR-based assays in 71% of the detections. In conclusion, although limited by the a priori knowledge of viral reference genome sequences, the proposed methodology can provide a first confined but substantial insight into the presence, concentration and types of methylated viral sequences in MBD-seq data at low additional cost.

Association between urine phthalate levels and poor attentional performance in children with attention-deficit hyperactivity disorder with evidence of dopamine gene-phthalate interaction.

Although there is some evidence supporting the existence of an association between prenatal maternal or postnatal child's urine phthalate metabolite concentrations and poor attentional performances, the interaction between urine phthalate metabolite levels and genetic variation for neuropsychological deficit of attention-deficit hyperactivity disorder (ADHD) has not been examined. The aim of this study was to determine whether phthalate metabolites in urine are associated with poor neuropsychological performance in children with ADHD, and whether such association is affected by genotype-phthalate interaction. A cross-sectional examination of urine phthalate metabolite concentrations and the continuous performance test (CPT) were performed in 179 Korean children with ADHD recruited from department of psychiatry of university hospital. Correlations between urine phthalate metabolite concentrations and the CPT scores were investigated, and the interaction of phthalate metabolite levels with the selected polymorphisms at major candidate genes for ADHD, namely dopamine receptor D4 (DRD4), dopamine transporter, α-2A-adrenergic receptor, and norepinephrine transporter genes. For the subjects with the DRD4 4/4 genotype, there were significant associations of the urine phthalate metabolite concentrations with the number of omission errors, the number of commission errors, and the response time variability scores on the CPT. However, for the subjects without the DRD4 4/4 genotype, no significant associations were found. The results of this study suggest a possible association between phthalate metabolite concentrations and poor attentional performances of ADHD as well as a genetic influence on this association. Further prospective and epigenetic studies are needed to investigate causality and pathophysiological mechanisms.

Widely used food additive promotes colitis, obesity and metabolic syndrome, research shows

Emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter the gut microbiota composition and localization to induce intestinal inflammation that promotes the development of inflammatory bowel disease and metabolic syndrome, new research shows.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, afflicts millions of people and is often severe and debilitating. Metabolic syndrome is a group of very common obesity-related disorders that can lead to type-2 diabetes, cardiovascular and/or liver diseases. Incidence of IBD and metabolic syndrome has been markedly increasing since the mid-20th century.
The team fed mice two very commonly used emulsifiers, polysorbate 80 and carboxymethylcellulsose, at doses seeking to model the broad consumption of the numerous emulsifiers that are incorporated into almost all processed foods. They observed that emulsifier consumption changed the species composition of the gut microbiota and did so in a manner that made it more pro-inflammatory. The altered microbiota had enhanced capacity to digest and infiltrate the dense mucus layer that lines the intestine, which is normally, largely devoid of bacteria. Alterations in bacterial species resulted in bacteria expressing more flagellin and lipopolysaccharide, which can activate pro-inflammatory gene expression by the immune system.

Disturbance of Oligodendrocyte Function Plays a Key Role in the Pathogenesis of Schizophrenia and Major Depressive Disorder

The major psychiatric disorders such as schizophrenia (SZ) and major depressive disorder (MDD) are thought to be multifactorial diseases related to both genetic and environmental factors. However, the genes responsible and the molecular mechanisms underlying the pathogenesis of SZ and MDD remain unclear. We previously reported that abnormalities of disrupted-in-Schizophrenia-1 (DISC1) and DISC1 binding zinc finger (DBZ) might cause major psychiatric disorders such as SZ. Interestingly, both DISC and DBZ have been further detected in oligodendrocytes and implicated in regulating oligodendrocyte differentiation. DISC1 negatively regulates the differentiation of oligodendrocytes, whereas DBZ plays a positive regulatory role in oligodendrocyte differentiation. We have reported that repeated stressful events, one of the major risk factors of MDD, can induce sustained upregulation of plasma corticosterone levels and serum/glucocorticoid regulated kinase 1 (Sgk1) mRNA expression in oligodendrocytes. Repeated stressful events can also activate the SGK1 cascade and cause excess arborization of oligodendrocyte processes, which is thought to be related to depressive-like symptoms. In this review, we discuss the expression of DISC1, DBZ, and SGK1 in oligodendrocytes, their roles in the regulation of oligodendrocyte function, possible interactions of DISC1 and DBZ in relation to SZ, and the activation of the SGK1 signaling cascade in relation to MDD.

A large amount of mitochondrial toxic agents cross the placenta barrier

Researchers from the Hospital Clinic of Barcelona (Spain) have reviewed ten years' worth of scientific studies on mitochondrial toxicity in pregnant women. Exposure to toxic agents such as viruses, certain drugs, pesticides, alcohol and tobacco cause mitochondrial diseases about which very little is known, and which are transmitted from the mother to the foetus. Mitochondria can also suffer acquired pathologies due to, for example, exposure to toxic agents transferred from mother to child, causing conditions such as muscle weakness, inflammation of the pancreas and changes in the distribution and amount of body fat.

A team from the Muscle Research and Mitochondrial Function Laboratory at the Hospital Clinic of Barcelona has reviewed the little information there is available on mitochondrial toxicity in pregnant women over the last ten years. Their report, published in the International Journal of Environmental Research and Public Health, reviews more than 100 studies from the Pubmed/MEDLINE database.
In the report, the researchers propose alternatives in order to avoid any harmful effects for pregnant women and their babies based on two strategies: the search for toxicity markers and the avoidance of any contact with mitochondrial toxic agents.

Energy Drinks and Youth Self-Reported Hyperactivity/Inattention Symptoms - Academic Pediatrics

Objective

To describe patterns in sweetened beverage consumption by race/ethnicity and sex, documenting both the amount and types of sweetened beverages consumed; and to examine the association of sweetened beverage consumption with hyperactivity/inattention symptoms among middle school students in a single urban school district.

Methods

Middle school students (n = 1649; 47% Hispanic and 38% black, non-Hispanic) from 12 schools, randomly selected out of 27 district schools, completed health behavior surveys in fall 2011. Students reported quantity and types of sweetened beverages consumed in the past 24 hours and completed the 5-item Hyperactivity/Inattention subscale of the Strengths and Difficulties Questionnaire to measure symptoms.

Results

Amount and variety of reported sweetened beverage consumption (including energy drinks) were greater among boys versus girls and among black and Hispanic versus white students. Risk of hyperactivity/inattention increased by 14% for each additional sweetened beverage consumed, adjusting for age, race/ethnicity, sex, school lunch eligibility, family structure, and sugary food consumption. Students reporting consumption of energy drinks were 66% more likely to be at risk for hyperactivity/inattention after adjusting for number of drinks, other types of drinks consumed, and other potential confounders.

Conclusions

Results support recommendations to limit consumption of sweetened beverages and to avoid consumption of energy drinks among children. Interventions to reduce sweetened beverage consumption should explicitly focus on energy drinks and other emerging sweetened beverages such as sports and sweetened coffee drinks. More research is needed to understand the direction of effects and the mechanisms behind the association between sweetened beverages and hyperactivity/inattention symptoms.

Frontiers | Induction of the pro-inflammatory NF-kB-sensitive miRNA-146a by human neurotrophic viruses | Virology

A remarkably wide variety of human neurotrophic viruses—ranging from herpes simplex 1 (HSV-1;Herpesviridae; dsDNA genome) to Hantavirus (HTV; Bunyaviridae; (−)ssRNA genome) to human immunodeficiency virus (HIV; Retroviridae; (+)ssRNA genome) are associated with the rapid up-regulation of the NF-kB-sensitive pro-inflammatory microRNA-146a (miRNA-146a) in the host shortly after infection. This significant miRNA-146a up-regulation appears to be beneficial to the infecting virus as part of an immune-evasion strategy. Interestingly, miRNA-146a is also significantly up-regulated in several human central nervous system (CNS) disorders. These include Alzheimer's disease (AD) and prion disease where miRNA-146a participates in pro-inflammatory and innate-immune signaling. This opinion paper will comment on some recently clarified roles for the NF-kB-regulated, pro-inflammatory miRNA-146a in viral-induced cellular dysfunction, and how anti-miRNA-146a and/or related therapeutic strategies may be beneficial in the clinical management of a broad spectrum of viral-mediated CNS disease.

Toll-like receptor-2 deficiency induces schizophrenia-like behaviors in mice.

 Dysregulation of the immune system contributes to the pathogenesis of neuropsychiatric disorders including schizophrenia. Here, we demonstrated that toll-like receptor (TLR)-2, a family of pattern-recognition receptors, is involved in the pathogenesis of schizophrenia-like symptoms. Psychotic symptoms such as hyperlocomotion, anxiolytic-like behaviors, prepulse inhibition deficits, social withdrawal, and cognitive impairments were observed in TLR-2 knock-out (KO) mice. Ventricle enlargement, a hallmark of schizophrenia, was also observed in TLR-2 KO mouse brains. Levels of p-Akt and p-GSK-3α/β were markedly higher in the brain of TLR-2 KO than wild-type (WT) mice. Antipsychotic drugs such as haloperidol or clozapine reversed behavioral and biochemical alterations in TLR-2 KO mice. Furthermore, p-Akt and p-GSK-3α/β were decreased by treatment with a TLR-2 ligand, lipoteichoic acid, in WT mice. Thus, our data suggest that the dysregulation of the innate immune system by a TLR-2 deficiency may contribute to the development and/or pathophysiology of schizophrenia-like behaviors via Akt-GSK-3α/β signaling.

Mothers can pass traits to offspring through bacteria's DNA

Commensal bacteria influence traits such as weight and behavior. But until now, researchers thought the bacteria that exerted these effects were acquired during a person's life. The study is the first to show that bacterial DNA can pass from parent to offspring in a manner that affects specific traits such as immunity and inflammation.
The researchers linked commensal bacteria in mice to the animals' susceptibility to a gut injury. Mice with certain inherited bacteria are susceptible to the injury, which is caused by exposure to a chemical. Female mice pass the bacteria to their offspring, making them vulnerable to the injury. Others carrying different bacteria are less susceptible.
In the short term, the findings may help scientists eliminate a significant "bug" in studies of genetically engineered mice. In several fields of research, scientists have been confronted intermittently with the sudden, unexplained appearance of new or altered traits in mice. The traits often spread from one mouse habitat to the next, suggesting a spreading microbial infection is responsible. But the traits also consistently pass from mother to offspring, suggesting a genetic cause.

Molecular Psychiatry - Cigarette smoking and thinning of the brain/'s cortex

"Cigarette smoking is associated with cognitive decline and dementia, but the extent of the association between smoking and structural brain changes remains unclear. Importantly, it is unknown whether smoking-related brain changes are reversible after smoking cessation. We analyzed data on 504 subjects with recall of lifetime smoking data and a structural brain magnetic resonance imaging at age 73 years from which measures of cortical thickness were extracted. Multiple regression analyses were performed controlling for gender and exact age at scanning. To determine dose–response relationships, the association between smoking pack-years and cortical thickness was tested and then repeated, while controlling for a comprehensive list of covariates including, among others, cognitive ability before starting smoking. Further, we tested associations between cortical thickness and number of years since last cigarette, while controlling for lifetime smoking. There was a diffuse dose-dependent negative association between smoking and cortical thickness. Some negative dose-dependent cortical associations persisted after controlling for all covariates. Accounting for total amount of lifetime smoking, the cortex of subjects who stopped smoking seems to have partially recovered for each year without smoking. However, it took ~25 years for complete cortical recovery in affected areas for those at the mean pack-years value in this sample. As the cortex thins with normal aging, our data suggest that smoking is associated with diffuse accelerated cortical thinning, a biomarker of cognitive decline in adults. Although partial recovery appears possible, it can be a long process."




Should We Continue to Feed Antibiotics to Livestock? (infograph)


Currently 80 percent of all antibiotics sold in the U.S. are given to poultry and livestock.
"Since the 1950s farmers have fed antibiotic growth promoters (AGPs) to livestock. Overusing these substances can create superbugs, pathogens that are resistant to multiple drugs and could be passed along to humans. Mindful of that, companies such as Perdue Farms have stopped using the drugs to make chickens gain weight faster.

Since Denmark banned AGPs in the 1990s, the major pork exporter says it's producing more pigs—and the animals get fewer diseases. Says Centers for Disease Control and Prevention epidemiologist Tom Chiller, "Antibiotics are miracle drugs that should only be used to treat diseases.""



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Promising results for new Alzheimer's therapy -- ScienceDaily

"Patients with Alzheimer's disease suffer a selective and early breakdown of so-called cholinergic nerve cells, which require a specific nerve growth factor (NGF) -- essentially a group of proteins necessary for cell growth and survival -- to function. As NGF levels decline, the cholinergic nerve cells begin to degrade and the patient's condition slowly deteriorates.
In an attempt to curb the breakdown of the cholinergic nerve cells, researchers at Karolinska Institutet's Centre for Alzheimer's Research and their colleagues at Karolinska University Hospital's neurosurgery clinic and the Danish biotech company NsGene introduced NGF directly into the brains of Alzheimer's patients. To do this, they used NGF-producing cell capsules, placing them in the basal fore-brain where the cholinergic cells reside using precision stereotactic surgery. There the capsules, which can easily be removed, release NGF to the surrounding cells in order to prevent their degradation"

"Our results show that when the patients received NGF, there was a significant increase in ChAT in the CSF," says Dr Taher Darreh-Shori, one of the researchers involved in the study. "The patients that exhibited this increase were also those that responded best to the treatment. Our PET scans also showed an increase in cholinergic cell activity and metabolism in the brain."
In addition, the researchers were able to detect a retardation of memory impairment over time compared with untreated patients. While all this suggests that cholinergic functionality improved in the Alzheimer's patients who had received NGF therapy, the team adds the caveat that far-reaching conclusions should not be drawn from the results:

Investigation reveals network of links between public health scientists and sugar industry -- ScienceDaily

"Public health scientists and a government committee working on nutritional advice receive funding from the very companies whose products are widely held to be responsible for the obesity crisis, an investigation by The BMJ reveals. Recipients of research funding from sugar and other related industries include members of the Scientific Advisory Committee on Nutrition (SACN), which is currently updating official advice on carbohydrates consumption, and researchers working for the Medical Research Council's Human Nutrition Research unit (HNR)."



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Metagenomic Sequencing Indicates That the Oropharyngeal Phageome of Individuals With Schizophrenia Differs From That of Controls.

Mucosal sites such as the oropharynx contain a wide range of microorganisms, collectively designated as the microbiome. The microbiome can affect behavior through a number of neurobiological and immunological mechanisms. Most previous studies have focused on the bacterial components of the microbiome. However, the microbiome also includes viruses such as bacteriophages, which are viruses that infect bacteria and alter their metabolism and replication. We employed metagenomic analysis to characterize bacteriophage genomes in the oral pharynx of 41 individuals with schizophrenia and 33 control individuals without a psychiatric disorder. This analysis was performed by the generation of more than 100000000 sequence reads from each sample and the mapping of these reads to databases. We identified 79 distinct bacteriophage sequences in the oropharyngeal samples. Of these, one bacteriophage genome, Lactobacillus phage phiadh, was found to be significantly different in individuals with schizophrenia (P < .00037, q < 0.03 adjusted for multiple comparisons). The differential levels of Lactobacillus phage phiadh remained significant when controlling for age, gender, race, socioeconomic status, or cigarette smoking (P < .006). Within the group of individuals with schizophrenia, the level of Lactobacillus phage phiadh correlated with the prevalence of immunological disorders as well as with the administration of valproate, which has been shown in animal models to alter the microbiome. The bacteriophage composition of the oropharynx in individuals with schizophrenia differs from that of controls. The biological consequences of this difference and the potential effects of altering bacteriophage levels through therapeutic interventions are worthy of further investigation.

Exposure to mercury, seafood associated with risk factor for autoimmune disease -- ScienceDaily

 "The findings, which appear in Environmental Health Perspectives, found that mercury -- even at low levels generally considered safe -- was associated with autoimmunity. Autoimmune disorders, which cause the body's immune system to attack healthy cells by mistake, affects nearly 50 million Americans and predominately women."




JAMA Network | Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome:  An IOM Report on Redefining an Illness


Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multisystem and often long-lasting disorder, with manifestations that can cause substantial morbidity and can severely impair patients’ health and well-being. It is estimated that between 836 000 and 2.5 million individuals are affected in the United States.1,2 Patients with ME/CFS are typically unable to perform their normal activities, and as many as one-fourth are homebound or bedridden, sometimes for extended periods.3 As a result, the personal and social effects and ramifications of this disease are enormous.

However, ME/CFS is poorly accepted and poorly understood, and the characteristics necessary to make the diagnosis are contested. Patients’ concerns are often met with dismay and skepticism, if not outright dismissal. Clinicians, in turn, are confronted by competing definitions, which were usually developed for research and are quite complex and difficult to implement in a busy clinical practice. Patients who are fortunate enough and persistent enough to receive a correct diagnosis frequently report long delays before their disorder was identified. It is almost certainly the case that the majority of affected patients are never diagnosed. This is unfortunate because effective symptom management is often available, whereas the wrong interventions can make symptoms worse.

Making the diagnosis is essential for providing appropriate care. To that end, the Department of Health and Human Services (HHS), together with the National Institutes of Health, US Social Security Administration, US Food and Drug Administration, Centers for Disease Control and Prevention, and Agency for Healthcare Research and Quality, tasked the Institute of Medicine (IOM) to develop “evidence-based clinical diagnostic criteria for ME/CFS for use by clinicians, using a consensus-building methodology,” with input from patients and clinicians; to “recommend whether new terminology for ME/CFS should be adopted”; and to create plans for disseminating these conclusions to clinicians.

Energy drinks significantly increase hyperactivity in schoolchildren, study finds -- ScienceDaily

Middle-school children who consume heavily sweetened energy drinks are 66% more likely to be at risk for hyperactivity and inattention symptoms, a new study led by the Yale School of Public Health has found.The finding has implications for school success and lends support to existing recommendations to limit the amount of sweetened beverages schoolchildren drink. The authors also recommend that children avoid energy drinks, which in addition to high levels of sugar also often contain caffeine. The study is published in the journal Academic Pediatrics
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Translational Psychiatry - Influence of maternal infections on neonatal acute phase proteins and their interaction in the development of non-affective psychosis

Although primary infections with Toxoplasma gondii or herpes viruses during pregnancy are established teratogens, chronic maternal infections with these pathogens are considered far less serious. However, such chronic infections have been associated with neuropsychiatric disorders in the offspring. The risks of non-affective psychoses, including schizophrenia, in offspring associated with these exposures during pregnancy have not been completely defined. We used data from neonatal dried blood samples from 199 cases of non-affective psychosis and 525 matched controls (born 1975–1985). We measure immunoglobulin G antibodies directed at T. gondii, cytomegalovirus and herpes simplex virus type-1 and -2, as well as levels of nine acute phase proteins (APPs). We assessed the interaction between maternal antibodies and neonatal APP in terms of risk of non-affective psychosis. Among controls, maternal exposure to T. gondii or cytomegalovirus, but not to the other herpes viruses, was associated with significantly higher levels of neonatal APPs. Among cases, none of the maternal exposures were associated with any significant change in APPs. We observed increased RR for non-affective psychosis associated with maternal infection with T. gondii (odds ratio 2.1, 95% confidence interval 1.1–4.0) or cytomegalovirus (1.7, 0.9–3.3) only among neonates with low APP levels. These findings suggest that chronic maternal infection with T. gondii or cytomegalovirus affect neonatal markers of innate immunity. Deficient fetal immune responses in combination with maternal chronic infections may contribute to subsequent risk for psychosis. A greater understanding of the maternal–fetal immunological interplay may ultimately lead to preventive strategies toward neuropsychiatric disorders.