Reduced production of myelin, a type of protective nerve fibre that is lost in diseases like multiple sclerosis, may also play a role in the development of mental illness, according to researchers at the Graduate School of Biomedical Sciences at Mount Sinai School of Medicine.
Myelin is an insulating material that wraps around the axon, the threadlike part of a nerve cell through which the cell sends impulses to other nerve cells. New myelin is produced by nerve cells called oligodendrocytes both during development and in adulthood to repair damage in the brain of people with diseases such as multiple sclerosis (MS).
A new study led by Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomics; and Neurology at Mount Sinai, determined that depriving mice of social contact reduced myelin production, demonstrating that the formation of new oligodendrocytes is affected by environmental changes. This research provides further support to earlier evidence of abnormal myelin in a wide range of psychiatric disorders, including autism, anxiety, schizophrenia and depression.
‘We knew that a lack of social interaction early in life impacted myelination in young animals but were unsure if these changes would persist in adulthood,’ said Dr. Casaccia, who is also Chief of the Center of Excellence for Myelin Repair at the Friedman Brain Institute at Mount Sinai School of Medicine. ‘Social isolation of adult mice causes behavioural and structural changes in neurons, but this is the first study to show that it causes myelin dysfunction as well.’
Dr. Casaccia’s team isolated adult mice to determine whether new myelin formation was compromised. After eight weeks, they found that the isolated mice showed signs of social withdrawal. Subsequent brain tissue analyses indicated that the socially isolated mice had lower-than-normal levels of myelin-forming oligodendrocytes in the prefrontal cortex, but not in other areas of the brain. The prefrontal cortex controls complex emotional and cognitive behaviour.
The researchers also found changes in chromatin, the packing material for DNA. As a result, the DNA from the new oligodendrocytes was unavailable for gene expression.
After observing the reduction in myelin production in socially-isolated mice, Dr. Casaccia’s team then re-introduced these mice into a social group. After four weeks, the social withdrawal symptoms and the gene expression changes were reversed.
‘Our study demonstrates that oligodendrocytes generate new myelin as a way to respond to environmental stimuli, and that myelin production is significantly reduced in social isolation,’ said Dr. Casaccia. ‘Abnormalities occur in people with psychiatric conditions characterised by social withdrawal. Other disorders characterised by myelin loss, such as MS, often are associated with depression. Our research emphasises the importance of maintaining a socially stimulating environment in these instances.’
At Mount Sinai, Dr. Casaccia’s laboratory is studying oligodendrocyte formation to identify therapeutic targets for myelin repair. They are screening newly-developed pharmacological compounds in brain cells from rodents and humans for their ability to form new myelin. EurekAlert

Scientists say they have developed a breath-test that can accurately tell if a person has bowel cancer. The test, which looks for exhaled chemicals linked to tumour activity, was able to identify a majority of patients with the disease.
The British Journal of Surgery reported an overall accuracy of 76%.
However, another scientist said it was unlikely a fully functioning and reliable breath-test would be available soon for the general public. Scientists are working on breath-tests for a host of other diseases, including several types of cancer, TB and diabetes.
If diagnosed and treated early, the chances of stopping cancer can be good, but there is often little or no outward sign of the disease until it has progressed significantly.
The current screening test for bowel cancer looks for signs of blood in the faeces, but only a small proportion of those who test positive actually have colorectal cancer, which means unnecessary and invasive further testing for many people.
The breath-test technology relies on the idea that the biology of tumours can lead to the production of specific ‘volatile organic compounds’, combinations of chemicals unlikely in a healthy person.
These can be found in small amounts in the breath of the patient, and early studies found dogs could be trained to identify them – although the latest study relies an electronic device to analyse breath gases.
The team from a hospital in Bari, southern Italy, compared the breath of 37 patients known to have bowel cancer with that of 41 ‘controls’ who were thought to be healthy.
The initial test identified the cancer patients with 85% accuracy, and although, when combined with a follow-up test, the overall result fell to 76%, the researchers were upbeat about its potential.
‘The present findings further support the value of breath-testing as a screening tool,’ they say.
It might be possible that the technique could help identify patients whose cancer was returning after treatment.
Bigger studies with a greater number of patients were now needed to fine-tune the test and confirm it worked, said Dr Donato Altomare and colleagues. BBC

Children with HIV have a 2.5 fold increased risk of atherosclerosis, according to research presented at EUROECHO and other Imaging Modalities 2012. Antiretroviral treatment, lipid lowering drugs and prevention with healthy lifestyles are needed to prevent early death from cardiovascular disease.
EUROECHO and other Imaging Modalities 2012 is the annual meeting of the European Association of Cardiovascular Imaging (EACVI), a registered branch of the European Society of Cardiology (ESC).
Antiretroviral treatment is prolonging the lives of HIV patients, who no longer die prematurely from the infection. But the treatment is not a cure, and the virus remains in the body.
‘The infection makes the body fight for its life, so the immune system is always activated and there is chronic inflammation,’ said Dr Talia Sainz Costa, principal investigator of the study and a paediatrician from Madrid, Spain.
In addition, many antiretroviral drugs increase bad (LDL) cholesterol and lower good (HDL) cholesterol. Dr Sainz Costa said:
‘Children with HIV will have high cholesterol for a long period and on top of that the virus causes chronic inflammation – both are bad for the arteries.’
Patients with HIV die 10 years prematurely from non-AIDS disease which includes cardiovascular diseases, cancer, liver and renal diseases.
‘This is especially important for children because they have been living with HIV since birth or even before,’ said Dr Sainz Costa. ‘By the time they are 50 years old they will have accumulated more toxicity from the treatment and more secondary effects from the infection and will be at an even greater risk of heart attacks and other complications.’
The present study aimed to discover whether children and adolescents already have early atherosclerosis damage. Carotid intima-media thickness (IMT), a marker of atherosclerosis, was measured using echocardiography in 150 children and adolescents with HIV and 150 age and sex matched healthy controls.
The researchers found that 17% of the HIV group were smokers compared to 11% of the control group. Dr Sainz Costa said:
‘Smoking levels in adolescents in Spain are known to be high. The even higher levels in the HIV group are probably related to low socio-economic status and very complex social/family backgrounds.’
After adjustment for age, sex, BMI and smoking status, HIV was independently associated with thicker IMT (p=0.005). Children and adolescents had a 2.5 fold increased risk of higher IMT due to HIV. Dr Sainz Costa said:
‘Our study shows that children and adolescents with HIV have arteries that are more rigid and less elastic, which means that the process of atherosclerosis has begun and they have increased risk of an infarct in the future.’
The researchers also found that frequencies of activated T CD4+ cells were higher among HIV-infected children and young adults (p=0.002). ‘This shows that the immune system is more active,’ said Dr Sainz Costa.
They concluded that clinicians need to take cardiovascular prevention more seriously in children and adolescents with HIV, while continuing to treat the HIV infection. Dr Sainz Costa said: ‘Cardiovascular disease has already put down roots in children and adolescents with HIV and we need to take preventive measures at this early stage. We should be more aggressive in treating their high cholesterol with medication – this practice is common in adults but rare in children.’ She added:
‘We also need to be stricter about healthy lifestyle advice. Many children and adolescents with HIV come from families with low socio-economic status and are more prone to smoking, poor diet and inactivity. This age group also struggles with adherence to medication which is another worry, but we should not let this decrease our efforts to prevent future complications.’
Dr Sainz Costa concluded: ‘HIV research is investigating ways to control the inflammation and immune activation with agents such as probiotics, aspirin and corticoids. In the meantime clinicians need to focus on ensuring their young patients with HIV take the antiretroviral treatment, take lipid lowering drugs when necessary, and adopt healthier lifestyles.’ European Society of Cardiology

About 10 percent of kids born with kidney defects have large alterations in their genomes known to be linked with neuro-developmental delay and mental illness, a new study by Columbia University Medical Center (CUMC) researchers has shown.
Congenital defects of the kidney and urinary tract account for nearly 25 percent of all birth defects in the US and are present in about 1 in every 200 births. Eventually, an evaluation for genomic alterations will be part of the standard clinical workup. Patients with congenital kidney disease—who are currently lumped into one category—will be placed in subgroups based on their genetic mutations and receive a more precise diagnosis.
‘This changes the way we should handle these kids,’ said kidney specialist Ali Gharavi, MD, associate professor of medicine at CUMC, associate director of the Division of Nephrology, and an internist and nephrologist at NewYork-Presbyterian Hospital.’
‘If a physician sees a child with a kidney malformation, that is a warning sign that the child has a genomic disorder that should be looked at immediately because of the risk of neuro-developmental delay or mental illness later in life,’ he said. ‘This is a major opportunity for personalising medical care. As we learn which therapies work best for each subgroup, the underlying genetic defect of the patient will dictate what approach to take.’
The current study was the result of a large collaborative effort of CUMC and other medical centers in the US, Italy, Poland, Croatia, Macedonia, and the Czech Republic. It was led by Dr. Gharavi and his colleague Simone Sanna-Cherchi, MD, an associate research scientist in CUMC’s Department of Medicine.
Until now, no studies have linked congenital kidney disease with neuro-developmental disorders.
‘If you talk to clinicians, they tell you that some of these kids behave differently,’ Dr. Sanna-Cherchi said. ‘There has been a general assumption, though, that behavioural or cognitive issues in children with chronic illnesses such as kidney disease stem from the child’s difficulty in coping with the illness. Our study suggests that in some cases, neuro-developmental issues may be attributable to an underlying genomic disorder, not the kidney disease.’
The mutations discovered by Drs. Gharavi and Sanna-Cherchi and their colleagues belong to a class of mutations called copy number variations (CNVs). CNVs are extra copies or deletions of DNA just large enough to contain several genes. When CNVs are present, the ‘dose’ of the affected genes is either lower or higher than normal, potentially leading to a health disorder.
Until the mid-2000s, when effective techniques for detecting CNVs were developed, scientists thought that CNVs caused only a small number of health disorders. Today, tens of thousands of different CNVs have been discovered and linked to several disorders—including autism, schizophrenia, and Parkinson’s disease.
To see if CNVs are involved in congenital kidney defects, Drs. Gharavi and Sanna-Cherchi scanned the genomes of 522 individuals with small and malformed kidneys from medical centres in Europe and United States. About 17 percent of the patients carried a CNV that appeared to contribute to their kidney disorder.
In studies of children with previously discovered CNVs, most of the CNVs had been linked to developmental delays or mental illness. In the current study, about 1 in 10 children had a CNV linked to developmental delays or mental illness.
Though it remains unclear why kidney malformations and neurodevelopment are linked in some cases, it is possible that the same genes involved in kidney development are involved in brain development, Dr. Gharavi said. University of Columbia

Hot flushes are not ‘in the head,’ but new research suggests they may start there. A UA research team has identified a region in the brain that may trigger the uncomfortable surges of heat most women experience in the first few years of menopause.
Hot flushes – also called hot flashes – affect millions of people, and not just women. Yet, it is still unclear what causes the episodes of temperature discomfort, often accompanied by profuse sweating.
Now a team of researchers around Dr. Naomi Rance, a professor in the department of pathology at the UA College of Medicine, has come closer to understanding the mechanism of hot flushes, a necessary step for potential treatment options down the road.

The team identified a group of brain cells known as KNDy neurons as a likely control switch of hot flushes. KNDy neurons (pronounced ‘candy’) are located in the hypothalamus, a portion of the brain controlling vital functions that also serves as the switchboard between the central nervous system and hormone signals.

‘Although the KNDy neurons are a very small population of cells, our research reveals that they play extremely important roles in how the body controls its energy resources, reproduction and temperature,’ said Melinda Mittelman-Smith, who led the study as part of her doctoral thesis. ‘They are true multitaskers.’

By studying KNDy neurons in rats, the research team created an animal model of menopause to elucidate the biological mechanisms of temperature control in response to withdrawal of the hormone oestrogen, the main trigger of the changes that go along with menopause.

They discovered that tail skin temperature was consistently lower in rats whose KNDy neurons were inactivated, suggesting the neurons control a process known as vasodilation, or widening of the blood vessels to increase blood flow through the skin.

‘The hallmark of hot flushes is vasodilation,’ explained Rance, who also is a neuropathologist at The University of Arizona Medical Center. ‘When you flush, your skin gets hot and you can see the redness of the skin. It is an attempt of the body to get rid of heat, just like sweating. Except that if you were to measure core temperature at that point, you would find it is not even elevated.’

Although the results are not yet directly applicable in helping individuals affected by hot flushes, they mark a necessary first step, Rance said.

‘Obviously we can’t do these studies in women, and only if we understand the mechanism is there a chance of developing therapies. All that is known so far is that dwindling estrogen levels have something to do with it but anything after that is a black box.’