The brain and mental health

PROFILE: A new scan for autism

Christine Ecker
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Dr Christine Ecker has developed a new way of diagnosing autism from a 15-minute brain scan.

Christine is a neuroscientist, and she currently works as a lecturer in neuro-imaging at the Institute of Psychiatry (IoP) , King’s College London. She works on the MRC-funded Autism Imaging Multicentre Study (AIMS), a major research project exploring the relationship between genes and brain development in people with autism. AIMS is being carried out by the IoP and the universities of Oxford and Cambridge.

“Our team works with people with autism spectrum disorder and we’re mainly interested in brain structure and brain functioning; how the brain works in autism,” says Christine.

People with autism mainly have difficulty with social interaction and communication. It is a spectrum condition, so people can be affected by the condition to varying degrees and it is complex, involving many different interlinked factors. At the moment it is diagnosed on the basis of a person’s behaviour. But this is not always easy, as Christine explains:

“Diagnosis isn’t too complicated in children, because the defining symptoms start to appear around the age of four. But autism was only categorised as a disorder 10 or 15 years ago, so there are still a large number of undiagnosed adults out there, and diagnosing adults is a lot more problematic.

We give people tasks to do and interview their parents, but often that’s not too reliable because the people we see can be middle-aged, their parents might be in their seventies or eighties and you’ve got to ask them to remember how their son or daughter was at the age of four or five. So what we are trying to establish is a set of bio-markers for autism, to help with the diagnosis.”

In 2010, Christine and her colleagues began using a new analytical technique being developed at the IoP to look at autism. The technique they have developed involves doing a magnetic resonance imaging (MRI) scan of the person’s brain and then ‘training’ a computer programme to analyse the differences in brain structure between people with brain disorders and healthy volunteers. The technique is extremely sensitive to all kinds of minute differences, such as volume, curvature and the pattern of folding in various parts of the brain. It puts these minute measurements together and then makes a prediction.

“The computer software will find a pattern of brain regions that are different between the two groups,” says Christine. “Once you’ve found this pattern you can scan someone new – and the computer programme will compare it to the sample it already has and then predict how likely it is that the person has autism.”

The team tested the technique on two sets of scans from around 40 patients from AIMS, half of whom had autism. In the first sample, which looked only at the volume of grey matter in the brain, the technique diagnosed autism with around 86 per cent accuracy. In the second sample, which measured all of the other features besides just grey matter volume, the accuracy was 90 per cent.

“What is new and exciting about our research is that for the very first time we can say something about individual brains. Traditionally we’ve only ever been able to look at mean differences between groups of people with autism and groups of healthy people. This could pave the way for a more individual approach to diagnosis and treatment”

Christine’s next challenge is to discover whether the scan will work in a clinical setting.

“We’re going to compare how the software performs in comparison to the conventional diagnosis. If it turns out that the test is still accurate then we can start with larger clinical trials. We’re hoping to scan the next 100 people by the end of 2011 and move onto larger clinical trials in 2012,” she says.

“I don’t think the brain scan will necessarily replace the conventional behavioural diagnosis, but it will add important extra information in cases where psychiatrists can’t be sure if someone has autism by using the conventional means.”

So if these studies eventually prove that the scan is an effective way of diagnosing autism, what will this mean for patients?

Christine says: “For most people, getting a diagnosis is very important because it unlocks access to specialist services. And of course it’s important to diagnose the condition as early and reliably as possible and particularly in adults where the diagnosis is very complicated and very time and cost intensive. So if we could diagnose autism with a 15-minute brain scan and patients don’t have to bring their parents along, it would make the diagnostic process itself a lot more comfortable for them.”

Achievements

New hope for Parkinson’s transplant treatment

Researchers funded by the MRC and Imperial College London have reopened the possibility of using a transplant treatment to relieve the symptoms of Parkinson’s disease.

In the 1990s researchers showed that it was possible to reverse the damage caused by Parkinson’s disease by transplanting brain cells from donated fetal brains into patients suffering from the disease. But when it emerged a few years later that the transplants also caused some patients to suffer from jerky, involuntary movements, this approach was abandoned.

To find out more about the cause of these side effects, a research team led by Dr Marios Politis at the MRC Clinical Sciences Centre in London scanned the brains of three patients who had received brain cell transplants. The scans showed that the involuntary movements were caused by malfunctioning nerve cells in the area of the brain where the transplant had taken place. The team also found that they could treat the movements with a drug which desensitises these nerve cells. They hope this discovery will lead to a resurgence in clinical trials in this area.

Dr Politis commented: “We are thrilled that this discovery could revive this promising area of research. We know that the benefits of this treatment could last up to 16 years, and we look forward to bringing this treatment one step closer to a reality for Parkinson’s patients.”

Re-starting the body clock

Most living creatures have an internal 24-hour body clock. This is a complex system of molecules in every cell that drives natural body processes known as circadian rhythms, such as our sleep and wake cycles. Disruption to these cycles can cause jet-lag after a long-haul flight, but can also play a role in psychiatric disorders.

Scientists funded by the MRC and the Biotechnology and Biological Sciences Research Council have now discovered a way to reset and restart this body clock in mice.

The clock works as a series of rises and falls in levels of the molecules, like a series of ‘ticks’. Daylight and darkness are important for re-setting the clock and fine adjustments are made by several enzymes, including one called casein kinase 1. Casein kinase 1 facilitates a drop in body clock molecules inside cells, so any changes in its activity can adjust the ‘ticking’ from 24 hours to a shorter or longer time period. In mice whose body clocks had been completely shut down, and in mouse tissue samples, the scientists were able to re-start the circadian rhythms using a drug to inhibit the activity of casein kinase 1.

Dr Michael Hastings, who led the work for the MRC Laboratory of Molecular Biology in Cambridge, alongside teams from the University of Manchester and pharmaceutical company Pfizer, explained: “Our findings suggest that by using drugs to inhibit casein kinase 1 we could treat conditions associated with disrupted circadian rhythms, such as bipolar disorder, jet lag and the negative health impacts of shift work.”

World’s first blood test for vCJD

The world’s first accurate blood test for variant Creutzfeldt-Jakob disease (vCJD) has been developed by MRC scientists, in collaboration with the NHS National Prion Clinic. vCJD is a brain disease caused by infectious agents called prions, and causes personality change, loss of body function and eventually death. At the moment, a clear diagnosis can be made only once serious and often irreversible symptoms of the disease have developed. There is also a chance that those unknowingly carrying vCJD could pass on the infection to others, for example through blood transfusions.

The highly sensitive new blood test consists of a ‘capture matrix’ based on metal particles, to which prions in the blood sample stick. Antibodies are then used to pick up the presence of prions which can be detected at one part per ten billion. The scientists tested 190 samples, including 21 from individuals known to have vCJD and the test was shown to be 100 per cent specific.

Lead author Dr Graham Jackson, programme leader at the MRC Prion Unit in Cambridge, said: “Although further larger studies are needed to confirm its effectiveness, this is the best hope yet of a successful early diagnostic test for vCJD. It could potentially go on to allow blood services to screen the population for vCJD infection, assess how many people in the UK are silent carriers and prevent onward transmission of the disease.”

Psychosis linked to altered brain chemistry

Patients who develop a psychosis, such as schizophrenia, show an increased capacity to make the brain chemical messenger dopamine, a new study has shown.

Dr Oliver Howes, group head at the MRC Clinical Sciences Centre in London, and colleagues at the Institute of Psychiatry, King’s College London, used a brain scanning technique (PET imaging) to measure patients’ capacity to make dopamine. They also scanned healthy volunteers and people with psychiatric problems who got better, and then compared the three groups. Besides the discovery that psychosis patients are able to produce more dopamine, the team also found that greater capacity to make dopamine was linked to more severe symptoms in those who developed psychosis. Dr Howes’ more recent research has suggested that the abnormal dopamine production capacity increases further with the onset of psychosis.

He said: “Psychotic illnesses such as schizophrenia are one of the top ten health problems in young adults worldwide; our finding is an important clue as to what causes them.” “As there was no change in the dopamine function of patients with psychiatric problems who got better, it appears that altered dopamine function is specific to the later development of psychosis.” The team is now carrying out research to see if the scan can be used as a predictive test, and to help develop preventive treatments. This has the potential to save many lives, because around one in 10 people with schizophrenia die from suicide, usually in the first few years after the illness starts.

Early years education staves off dementia in later life

By the time we die, almost all of us will have some physical evidence of dementia in our brains, even if the illness has not taken hold and caused significant memory problems. It had previously been suggested that there was a relationship between the number of years spent in education earlier on in life and the level of damage caused to the brain by the time people died.

Professor Carol Brayne at the MRC Cognitive Function and Ageing Co-operative at Cambridge University has led two of the largest long-term cohort studies, including the MRC-funded Cognitive Function and Ageing Study (MRC CFAS), working in collaboration with a third cohort based in Finland, to see whether a longer-term education can help reduce a person’s risk of developing dementia, or whether education in fact helps the brain make itself more resilient to the onslaught of neurodegenerative diseases.

Professor Brayne commented: “Our study showed that education in early life appears to enable some people to cope with a lot of changes in their brain before dementia symptoms emerge, despite the fact that people at higher education levels were just as likely to show physical signs of dementia in their brains at death as those who had studied less.

“We found that for each additional year of education there is an 11 per cent decrease in risk of developing physical symptoms of dementia. This study provides strong support for educational investment early in a person’s life which should have an impact on society and the whole lifespan.”

Word-learning discovery could help stroke patients

Researchers at the MRC Cognition and Brain Sciences Unit in Cambridge have found that after just 15 minutes of listening to a new word, the brain creates new networks of neurons to make up a long-term memory trace (a change in brain tissue which forms a memory). This process happens far faster than was previously thought.

The researchers recorded electrical signals in the brains of healthy volunteers while they listened to repetitions of new made-up words and familiar words. The scientists analysed how the brain activity changed over time as the made-up word became more and more familiar. Brain activity in response to these new words increased until the new memory traces were virtually indistinguishable from the memory traces of an already familiar word.

Dr Yury Shtyrov, who led the research, said: “Even a little practice can lead to changes in the brain and the formation of new brain networks that help us to memorise words. Faster rehabilitation may be possible if treatments for people with brain damage, such as stroke patients, target the brain’s ability to rapidly create these memory traces.”

Sibling study sheds light on addiction

A personality trait known as impulsivity is likely to be an inherited risk factor predisposing individuals to drug addiction, according to research led by Dr Karen Ersche at the MRC-funded Behavioural and Clinical Neuroscience Institute at the University of Cambridge.

By studying 30 pairs of siblings, one of whom was drug-dependent and one of whom was not, and comparing them to 30 unrelated non-drug users, Dr Ersche was able to establish a new understanding of the relationship between drug addiction and two character traits: impulsivity, acting on the spur of the moment; and sensation-seeking, pursuing excitement and sensations to stave off boredom.

People who are dependent on cocaine reported significantly higher levels of impulsivity than healthy volunteers. Their siblings also reported increased levels of impulsivity, although not as high as their drug-dependent brother or sister. In contrast, sensation-seeking personality traits were increased only in those who were drug-dependent, suggesting that sensation-seeking is a result of drug abuse, rather than a predisposing cause.

Dr Ersche explained: “Our findings give us an important insight into why some people are more vulnerable to drug addiction than others. We can’t change people’s personality traits, but if we know which individuals are more at risk of developing drug addiction we can target preventative strategies more effectively.”