Gene Linked to Autism and Intellectual Disability

Autism spectrum disorder and intellectual disability often occur together and may even share similar genetic causes. Researchers reporting in the Cell Press journal Cell Reports have now linked mutations in a particular gene to the two disorders in humans. By revealing these genetic changes and their potential impact on common brain processes, researchers may uncover treatment approaches that could benefit a variety of patients.

In a study of four families with a total of 16 individuals affected by a spectrum of cognitive and social impairments, the research team, led by investigators from Boston Children’s Hospital and Harvard Medical School, discovered two mutations in the CC2D1A gene that prevent the gene’s expression. When inherited from both parents, the lack of gene expression can cause mild to severe intellectual disability, autism, and/or seizures. The scientists then explored the function of this gene through experiments in mice.

Harvard Medical School

“A neuron must perform a very complex balancing act to respond to signals from other cells, and we found that CC2D1A is a key component in controlling this balance,” says senior author Dr. Christopher Walsh. A critical part of that balance involves the control of a signaling pathway that relies on NF-kappaB, a protein necessary for the survival and function of neurons. Reducing CC2D1A expression in mice led to decreased complexity of neurons and to increased NF-kappaB activity. Furthermore, the effects of CC2D1A depletion in neurons could be reversed by treating the mice with compounds that inhibit NF-kappaB activity.

“We hope that in the future, by fully understanding how this gene affects signaling in the brain, we may be able to identify drugs to restore the normal signaling balance in neurons and improve cognitive and social function in patients,” says lead author Dr. M. Chiara Manzini. “In addition, by studying how the same exact genetic change can cause either intellectual disability or autism, we can explore how these disorders originate and where they overlap.”

The researchers plan to investigate what percentage of individuals individuals with intellectual disability and autism may carry CC2D1A mutations and to determine whether other genes affect neurons in a similar fashion.

- MFP News Services
- 10/21/14

High-Salt Diet May Double Threat of Heart Disease for Diabetic Patients

Washington, DC — People with Type 2 diabetes who eat a diet high in salt face twice the risk of developing cardiovascular disease as those who consume less sodium, according to a new study published in the Endocrine Society’s Journal of Clinical Endocrinology & Metabolism.

Diabetes occurs when there is too much sugar in the bloodstream. People develop Type 2 diabetes when their bodies become resistant to the hormone insulin, which carries sugar from the blood to cells.

According to the U.S. Centers for Disease Control and Prevention, about 29.1 million Americans have some form of diabetes. This population is at risk for heart disease. Between 2003 and 2006, cardiovascular disease death rates were about 1.7 times higher among adults diagnosed with diabetes than those who were not, according to the CDC’s 2014 National Diabetes Statistics Report.

“The study’s findings provide clear scientific evidence supporting low-sodium diets to reduce the rate of heart disease among people with diabetes,” said the study’s first author, Chika Horikawa, RD, MSc, CDE, of the University of Niigata Prefecture in Niigata, Japan. “Although many guidelines recommend people with diabetes reduce their salt intake to lower the risk of complications, this study is among the first large longitudinal studies to demonstrate the benefits of a low-sodium diet in this population.”

Niigata University

The nationwide cohort study surveyed participants in the Japan Diabetes Complications Study who were between the ages of 40 and 70 and had been diagnosed with diabetes. Participants were identified at 59 outpatient centers and universities across Japan. In all, 1,588 people responded to a survey about their diets, including sodium intake. The researchers reviewed data on cardiovascular complications participants experienced over the course of eight years.

Researchers divided the participants into four groups based on their sodium intake. The analysis found people who ate an average of 5.9 grams of sodium daily had double the risk of developing cardiovascular disease than those who ate, on average, 2.8 grams of sodium daily. The effects of a high-sodium diet were exacerbated by poor blood sugar control.

“To reduce the risk of developing cardiovascular disease, it is important for people who have Type 2 diabetes to improve their blood sugar control as well as watch their diet,” Horikawa said. “Our findings demonstrate that restricting salt in the diet could help prevent dangerous complications from diabetes.”

- MFP News Services
- 10/20/14

Antipsychotic Drugs Linked to Decrease in Brain Volume

A study published recently has confirmed a link between antipsychotic medication and a slight, but measureable, decrease in brain volume in patients with schizophrenia. For the first time, researchers have been able to examine whether this decrease is harmful for patients’ cognitive function and symptoms, and noted that over a nine year follow-up, this decrease did not appear to have any effect.

As we age, our brains naturally lose some of their volume – in other words, brain cells and connections. This process, known as atrophy, typically begins in our thirties and continues into old age. Researchers have known for some time that patients with schizophrenia lose brain volume at a faster rate than healthy individuals, though the reason why is unclear.

Now, in a study published in the open access journal PLOS ONE, a team of researchers from the University of Oulu, Finland, and the University of Cambridge has identified the rate of decrease in both healthy individuals and patients with schizophrenia. They also documented where in the brain schizophrenia patients have more atrophy, and have examined links between atrophy and antipsychotic medication.

University of Cambridge

By comparing brain scans of 33 patients with schizophrenia with 71 control subjects over a period of 9 years – from age 34 to 43 – the researchers were able to show that schizophrenia patients lost brain volume at a rate of 0.7% each year. The control participants lost brain volume at a rate of 0.5% per year.

Scientists have previously speculated that antipsychotic medication used to treat schizophrenia may be linked to this decrease in brain volume. Today’s research confirms this association, showing that the rate of decrease in volume was greater when the dose of medication was higher. However, the mechanisms behind this – and whether it was in fact the medication that was causing this greater loss of tissue – are not clear. Some researchers have previously argued that whilst older antipsychotic medications might cause brain volume decreases, newer antipsychotic medications may protect against these decreases. However, today’s research suggests that both classes of antipsychotic medication are associated with similar declines in brain volume.

The researchers also looked at whether there was any link between the volume of brain lost and the severity of symptoms or loss of cognitive function, but found no effect.

Professor Juha Veijola from the Department of Psychiatry at the University of Oulu, Finland says: “We all lose some brain tissue as we get older, but people with schizophrenia lose it at a faster rate. We’ve shown that this loss seems to be linked to the antipsychotic medication people are taking. Research like this where patients are studied for many years can help to develop guidelines about when clinicians can reduce the dosage of antipsychotic medication in the long term treatment of people with schizophrenia.”

“It’s important to stress that the loss of brain volume doesn’t appear to have any effect on people over the nine year follow-up we conducted, and patients should not stop their medication on the basis of this research, ” adds Dr Graham Murray from the Behavioural and Clinical Neuroscience Institute and the Department of Psychiatry at University of Cambridge. “A key question in future will be to examine whether there is any effect of this loss of brain volume later in life. We need more research in larger studies with longer follow-ups to evaluate the significance of these brain changes.”

- MFP News Services
- 10/17/14