Opposite risk patterns for autism and schizophrenia are associated with normal variation in birth size: phenotypic support for hypothesized diametric gene-dosage effects.

Opposite phenotypic and behavioural traits associated with copy number
variation and disruptions to imprinted genes with parent-of-origin
effects have led to the hypothesis that autism and schizophrenia share
molecular risk factors and pathogenic mechanisms, but a direct
phenotypic comparison of how their risks covary has not been attempted.
Here, we use health registry data collected on Denmark's roughly 5
million residents between 1978 and 2009 to detect opposing risks of
autism and schizophrenia depending on normal variation (mean ± 1 s.d.)
in adjusted birth size, which we use as a proxy for diametric
gene-dosage variation in utero. Above-average-sized babies (weight,
3691-4090 g; length, 52.8-54.3 cm) had significantly higher risk for
autism spectrum (AS) and significantly lower risk for schizophrenia
spectrum (SS) disorders. By contrast, below-average-sized babies
(2891-3290 g; 49.7-51.2 cm) had significantly lower risk for AS and
significantly higher risk for SS disorders. This is the first study
directly comparing autism and schizophrenia risks in the same
population, and provides the first large-scale empirical support for the
hypothesis that diametric gene-dosage effects contribute to these
disorders. Only the kinship theory of genomic imprinting predicts the
opposing risk patterns that we discovered, suggesting that molecular
research on mental disease risk would benefit from considering
evolutionary theory.

A mycotoxin present in many types of food deteriorates neuroregeneration

chemical structure of the mycotoxin ochratoxin A
chemical structure of the mycotoxin ochratoxin A (Photo credit: Wikipedia)
Researchers at the Institute for Biomedical Sciences at CEU-UCH, in
cooperation with colleagues of University of Valencia, showed through in
vitro as well as in vivo experiments on lab animals the potential
negative effect on neuroregeneration caused by Ochratoxine A, a
mycotoxine found in many types of food, especially cereals and their
derivatives. The study showed that Ochratoxine A deteriorates the
formation of new neurons in the brain, a process called neurogenesis
that, in particular, takes place in the subventricular zone, which in
the adult brain is the largest of the neurogenic zones.

Air Pollution and Children: Neural and Tight Junction Antibodies and Combustion Metals, the Role of Barrier Breakdown and Brain Immunity in Neurodegeneration.

Millions of children are exposed to concentrations of air pollutants, including fine particulate matter (PM2.5), above safety standards. Mexico City Metropolitan Area (MCMA) megacity children show an early brain imbalance in oxidative stress, inflammation, innate and adaptive immune response-associated genes, and blood-brain barrier breakdown. We investigated serum and cerebrospinal fluid (CSF) antibodies to neural and tight junction proteins and environmental pollutants in 139 children ages 11.91 ± 4.2 y with high versus low air pollution exposures. We also measured metals in serum and CSF. MCMA children showed significantly higher serum actin IgG, occludin/zonulin 1 IgA, IgG, myelin oligodendrocyte glycoprotein IgG and IgM (p < 0.01), myelin basic protein IgA and IgG, S-100 IgG and IgM, and cerebellar IgG (p < 0.001). Serum IgG antibodies to formaldehyde, benzene, and bisphenol A, and concentrations of Ni and Cd were significantly higher in exposed children (p < 0.001). CSF MBP antibodies and nickel concentrations were higher in MCMA children (p = 0.03). Air pollution exposure damages epithelial and endothelial barriers and is a robust trigger of tight junction and neural antibodies. Cryptic 'self' tight junction antigens can trigger an autoimmune response potentially contributing to the neuroinflammatory and Alzheimer and Parkinson's pathology hallmarks present in megacity children. The major factor determining the impact of neural antibodies is the integrity of the blood-brain barrier. Defining the air pollution linkage of the brain/immune system interactions and damage to physical and immunological barriers with short and long term neural detrimental effects to children's brains ought to be of pressing importance for public health.

Artificial sweeteners linked to abnormal glucose metabolism

Artificial sweeteners, promoted as aids to weight loss and diabetes
prevention, could actually hasten the development of glucose intolerance
and metabolic disease; and they do it in a surprising way: by changing
the composition and function of the gut microbiota – the substantial
population of bacteria residing in our intestines. These findings, the
results of experiments in mice and humans, were published today in Nature.
Among other things, says Dr. Eran Elinav of the Weizmann Institute's
Immunology Department, who led this research together with Prof. Eran
Segal of Computer Science and Applied Mathematics Department, the
widespread use of artificial sweeteners in drinks and food may be
contributing to the obesity and diabetes epidemic that is sweeping much
of the world.


Artificial sweeteners induce glucose intolerance by altering the gut microbiota

▶ The Immunopathogenesis of Multiple Sclerosis - YouTube

Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders

Animal models indicate that maternal infection during pregnancy can
result in behavioral abnormalities and neuropathologies in offspring. We
examined the association between maternal inpatient diagnosis with
infection during pregnancy and risk of ASD in a Swedish nationwide
register-based birth cohort born 1984-2007 with follow-up through 2011.
In total, the sample consisted of 2,371,403 persons with 24,414 ASD
cases. Infection during pregnancy was defined from ICD codes. In the
sample, 903 mothers of ASD cases (3.7%) had an inpatient diagnosis of
infection during pregnancy. Logistic regression models adjusted for a
number of covariates yielded odds ratios indicating approximately a 30%
increase in ASD risk associated with any inpatient diagnosis of
infection. Timing of infection did not appear to influence risk in the
total Swedish population, since elevated risk of ASD was associated with
infection in all trimesters. In a subsample analysis, infections were
associated with greater risk of ASD with intellectual disability than
for ASD without intellectual disability. The present study adds to the
growing body of evidence, encompassing both animal and human studies,
that supports possible immune-mediated mechanisms underlying the
etiology of ASD.

Uncovering the Hidden Risk Architecture of the Schizophrenias: Confirmation in Three Independent Genome-Wide Association Studies

Objective
The authors sought to demonstrate that schizophrenia is a
heterogeneous group of heritable disorders caused by different genotypic
networks that cause distinct clinical syndromes.

Method
In a large genome-wide association study of cases with
schizophrenia and controls, the authors first identified sets of
interacting single-nucleotide polymorphisms (SNPs) that cluster within
particular individuals (SNP sets) regardless of clinical status. Second,
they examined the risk of schizophrenia for each SNP set and tested
replicability in two independent samples. Third, they identified
genotypic networks composed of SNP sets sharing SNPs or subjects.
Fourth, they identified sets of distinct clinical features that cluster
in particular cases (phenotypic sets or clinical syndromes) without
regard for their genetic background. Fifth, they tested whether SNP sets
were associated with distinct phenotypic sets in a replicable manner
across the three studies.

Results
The authors identified 42 SNP sets associated with a 70% or
greater risk of schizophrenia, and confirmed 34 (81%) or more with
similar high risk of schizophrenia in two independent samples. Seventeen
networks of SNP sets did not share any SNP or subject. These disjoint
genotypic networks were associated with distinct gene products and
clinical syndromes (i.e., the schizophrenias) varying in symptoms and
severity. Associations between genotypic networks and clinical syndromes
were complex, showing multifinality and equifinality. The interactive
networks explained the risk of schizophrenia more than the average
effects of all SNPs (24%).

Conclusions
Schizophrenia is a group of heritable disorders caused by a
moderate number of separate genotypic networks associated with several
distinct clinical syndromes.

Metagenomic analysis of double-stranded DNA viruses in healthy adults.

The Human Microbiome Project (HMP) was undertaken with the
goal of defining microbial communities in and on the bodies of healthy
individuals using high-throughput, metagenomic sequencing analysis. The
viruses present in these microbial communities, the `human virome¿, are
an important aspect of the human microbiome that is particularly
understudied in the absence of overt disease. We analyzed eukaryotic
double-stranded DNA (dsDNA) viruses, together with dsDNA replicative
intermediates of single-stranded DNA viruses, in metagenomic sequence
data generated by the HMP. 706 samples from 102 subjects were studied,
with each subject sampled at up to five major body habitats: nose, skin,
mouth, vagina, and stool. Fifty-one individuals had samples taken at
two or three time points 30 to 359 days apart from at least one of the
body habitats.ResultsWe detected an average of 5.5 viral genera in each
individual. At least 1 virus was detected in 92% of the individuals
sampled. These viruses included herpesviruses, papillomaviruses,
polyomaviruses, adenoviruses, anelloviruses, parvoviruses, and
circoviruses. Each individual had a distinct viral profile,
demonstrating the high interpersonal diversity of the virome. Some
components of the virome were stable over time.ConclusionsThis study is
the first to use high-throughput DNA sequencing to describe the
diversity of eukaryotic dsDNA viruses in a large cohort of normal
individuals who were sampled at multiple body sites. Our results show
that the human virome is a complex component of the microbial flora.
Some viruses establish long-term infections that may be associated with
increased risk or possibly with protection from disease. A better
understanding of the composition and dynamics of the virome may hold
important keys to human health.

Increased Alzheimer's risk linked to long-term benzodiazepine use - Medical News Today

The study found that benzodiazepine use for 3 months or more was associated with an increased risk of Alzheimer's disease of up to 51%. The longer the exposure to benzodiazepines, the greater the risk of Alzheimer's. Long-acting benzodiazepines were also found to increase risk more than short-acting benzodiazepines.

Maternal complement C1q and increased odds for psychosis in adult offspring

The presence of maternal antibodies to food and infectious antigens may
confer an increased risk of developing schizophrenia and psychosis in
adult offspring. Complement factor C1q is an immune molecule with
multiple functions including clearance of antigen–antibody complexes
from circulation and mediation of synaptic pruning during fetal brain
development. To determine if maternal C1q was associated with offspring
schizophrenia and psychosis, we evaluated 55 matched case–control
maternal serum pairs from the National Collaborative Perinatal Project.
Sample pairs were composed of mothers whose offspring developed
psychoses as adults and those whose offspring were free from psychiatric
disease. Matching criteria for offspring included birth date, delivery
hospital, race, and gender, with further matching based on mother's age.
IgG markers of C1q, bovine milk casein, egg ovalbumin, and wheat gluten
were measured with enzyme-linked immunosorbent assays. C1q levels were
compared to food antigen IgG and to previously generated data for
C-reactive protein, adenovirus, herpes simplex viruses, influenza
viruses, measles virus, and Toxoplasma gondii. C1q was significantly elevated in case mothers with odds ratios of 2.66–6.31 (conditional logistic regressions, p ≤ 0.008–0.05).
In case mothers only, C1q was significantly correlated with antibodies
to both food and infectious antigens: gluten (R2 = 0.26, p ≤ 0.004), herpes simplex virus type 2 (R2 = 0.21, p ≤ 0.02), and adenovirus (R2 = 0.25, p ≤ 0.006).
In conclusion, exposure to maternal C1q activity during pregnancy may
be a risk factor for the development of schizophrenia and psychosis in
offspring. Prenatal measurement of maternal C1q may be an important and
convergent screening tool to identify potentially deleterious immune
activation from multiple sources.

Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment.

Scientists discover how to 'switch off' autoimmune diseases

Scientists have made an important breakthrough in the fight against debilitating autoimmune diseases such as multiple sclerosis by revealing how to stop cells attacking healthy body tissue. Rather than the body’s immune system destroying its own tissue by mistake, researchers at the University of Bristol have discovered how cells convert from being aggressive to actually protecting against disease.
Scientists were able to selectively target the cells that cause autoimmune disease by dampening down their aggression against the body’s own tissues while converting them into cells capable of protecting against disease. This type of conversion has been previously applied to allergies, known as ‘allergic desensitisation’, but its application to autoimmune diseases has only been appreciated recently.
The Bristol group has now revealed how the administration of fragments of the proteins that are normally the target for attack leads to correction of the autoimmune response.
Most importantly, their work reveals that effective treatment is achieved by gradually increasing the dose of antigenic fragment injected.



Here's the paper:-

Sequential transcriptional changes dictate safe and effective antigen-specific immunotherapy

Borna disease virus (BDV) infection in psychiatric patients and healthy controls in Iran.

BACKGROUND:

Borna disease virus (BDV) is an evolutionary old RNA virus, which infects brain and blood cells of
humans, their primate ancestors, and other mammals. Human infection has been correlated to mood disorders and schizophrenia, but the impact of BDV on mental-health still remains controversial due to poor methodological and cross-national comparability.

METHOD:

This
first report from the Middle East aimed to determine BDV infection
prevalence in Iranian acute psychiatric disorder patients and healthy
controls through circulating immune complexes (CIC), antibodies (Ab) and
antigen (pAg) in blood plasma using a standardized triple enzyme immune
assay (EIA). Samples of 314 subjects (114 psychiatric cases, 69 blood
donors, and 131 healthy controls) were assayed and data analyzed
quantitatively and qualitatively.

RESULTS:

CICs revealed a BDV prevalence of one third (29.5%) in healthy Iranian controls (27.5%
controls; 33.3% blood donors). In psychiatric patients CIC prevalence
was higher than in controls (40.4%) and significantly correlating with
bipolar patients exhibiting overt clinical symptoms (p = 0.005, OR =
1.65). CIC values were significantly elevated in bipolar (p = 0.001) and
major depressive disorder (p = 0.029) patients as compared to controls,
and in females compared to males (p = 0.031).

CONCLUSION:

This study supports a similarly high prevalence of subclinical human BDV
infections in Iran as reported for central Europe, and provides again an
indication for the correlation of BDV infection and mood disorders.
Further studies should address the morbidity risk for healthy carriers
and those with elevated CIC levels, along with gender disparities.

PLOS Biology: Epstein-Barr Virus: The Path from Association to Causality for a Ubiquitous Human Pathogen

Bacterial Infection and Alzheimer's Disease: A Meta-Analysis.

The possibility of an infectious etiology for Alzheimer's disease (AD)
has been repeatedly postulated over the past three decades. We provide
the first meta-analysis to address the relationship between bacterial
infection and AD. Studies examining the association between AD and
spirochetal bacteria or Chlamydophila pneumoniae (Cpn) were identified
through a systematic search of the databases MEDLINE, EMBASE, PubMed,
and Google Scholar. Data combined from 25 relevant, primarily
case-control studies demonstrated a statistically significant
association between AD and detectable evidence of infection of either
bacterial group. We found over a ten-fold increased occurrence of AD
when there is detectable evidence of spirochetal infection (OR: 10.61;
95% CI: 3.38-33.29) and over a four-fold increased occurrence of AD in a
conservative risk estimate (OR 4.45; 95% CI: 2.33-8.52). We found over a
five-fold increased occurrence of AD with Cpn infection (OR 5.66; 95%
CI: 1.83-17.51). This study shows a strongly positive association
between bacterial infection and AD. Further detailed investigation of
the role of bacterial infection is warranted.

Mice Genetically Depleted of Brain Serotonin Do Not Display a Depression-like Behavioral Phenotype - ACS Chemical Neuroscience

Reductions in function within the serotonin (5HT) neuronal system have
long been proposed as etiological factors in depression. Selective
serotonin reuptake inhibitors (SSRIs) are the most common treatment for
depression, and their therapeutic effect is generally attributed to
their ability to increase the synaptic levels of 5HT. Tryptophan
hydroxylase 2 (TPH2) is the initial and rate-limiting enzyme in the
biosynthetic pathway of 5HT in the CNS, and losses in its catalytic
activity lead to reductions in 5HT production and release. The time
differential between the onset of 5HT reuptake inhibition by SSRIs
(minutes) and onset of their antidepressant efficacy (weeks to months),
when considered with their overall poor therapeutic effectiveness, has
cast some doubt on the role of 5HT in depression. Mice lacking the gene
for TPH2 are genetically depleted of brain 5HT and were tested for a
depression-like behavioral phenotype using a battery of valid tests for
affective-like disorders in animals. The behavior of TPH2–/–
mice on the sucrose preference test, tail suspension test, and forced
swim test and their responses in the unpredictable chronic mild stress
and learned helplessness paradigms was the same as wild-type controls.
While TPH2–/– mice as a group were not responsive to SSRIs, a
subset responded to treatment with SSRIs in the same manner as
wild-type controls with significant reductions in immobility time on the
tail suspension test, indicative of antidepressant drug effects. The
behavioral phenotype of the TPH2–/– mouse questions the role of 5HT in depression. Furthermore, the TPH2–/–
mouse may serve as a useful model in the search for new medications
that have therapeutic targets for depression that are outside of the 5HT
neuronal system.

Folate concentrations during pregnancy and autistic traits in the offspring. The Generation R Study

In a population-based study, we examined the associations of maternal plasma folate concentrations at 13 weeks of gestation and prenatal folic acid supplement use with autistic traits in the offspring at the age of six years. Parent-reported autistic traits were assessed using the Social Responsiveness Scale short form. Maternal folate was not associated with autistic traits in the offspring. In contrast, prenatal folic acid use was associated with less child autistic traits. Future research should focus on the timing of the potential effect of prenatal folate on the development of autistic traits in combination with clinical diagnosis of autism in the offspring.

Epstein-Barr virus (EBV) infection leaves lasting epigenetic imprint

Epstein-Barr virus (EBV) is a prevalent human herpesvirus affecting over
90% of the adult population worldwide. Most individuals harbor EBV
asymptomatically as lifelong infections. However, in rare cases, EBV is
associated with epithelial and B cell malignancies. The viral life cycle
is dependent on host epigenetic machinery to regulate viral gene
expression programs that ensure viral persistence and spread. Infection
with EBV can lead to epigenetic changes in the host cell as well.
Several EBV proteins interact with host epigenetic machinery, such as
the latent membrane proteins ability to induce the activity of the DNA
methyltransferases (DMNT) [1-3]. The consequences of which can best be seen in EBV-associated malignancies with the CpG island methylator phenotype (CIMP) [4, 5].
CIMP is where CpG islands upstream of tumor suppressors are
hypermethylated and this phenotype has a strong correlation with EBV.
Whether EBV directs the DNA methylation changes, or if the epigenetic
changes are due to the carcinogenic process are still being defined.

Junk food makes rats lose appetite for balanced diet

A diet of junk food not only makes rats fat, but also reduces their appetite for novel foods, a preference that normally drives them to seek a balanced diet, reports a study published in the open-access journal Frontiers in Psychology.