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Research breakthrough in schizophrenia

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WHAT comes to mind when you hear ‘schizophrenia’? Hallucinations and delusions? Cognitive impairment? Feeling withdrawn from everyone around you? Apathy? With all the above being symptoms of this mental disorder, and with 1 in every 100 people affected, each individual’s life becomes a relentless battle, struggling with habitual activities, social interaction, and general wellbeing and self-care.
Current treatments help to reduce the severity of symptoms and allow patients to maintain a more functional daily life. However, antipsychotic medications, which are typically required lifelong, are not guaranteed to work for all schizophrenia patients, with only about 4 in 5 people benefitting usually.
Advances in scanning have allowed researchers for the first time to show lower levels of a protein found in the connections between neurons in the living brains of people with schizophrenia.
The researchers, who conducted the scans at the psychiatric imaging facility at the MRC London Institute of Medical Sciences, say these changes could underlie the cognitive difficulties seen in schizophrenia and provide targets for research into new treatments.
Synapses are the junctions between neurons. Neurons communicate across the synapse via neurotransmitters; chemicals that transmit the nerve signal.
Researchers investigated the relationship between synaptic density and schizophrenia, questioning whether a reduction in these brain connections is present in schizophrenia and whether they result from treatment with antipsychotic drugs.
The study was inspired by findings from previous post-mortem studies that demonstrated synaptic reductions in the brains of schizophrenia patients compared to healthy controls.
Measuring synaptic protein levels in living patients was not possible before the development of a new PET (Positron Emission Tomography) radioactive tracer that binds to a specific protein associated with synapses. Being “one of the first centres in the world” to have access to this, Professor Oliver Howes, Head of the Psychiatric Imaging Group at the MRC LMS, and his team grasped this opportunity to investigate synaptic loss in schizophrenic brains through the synaptic marker protein SV2A, which is found on the nerve terminal preceding the synapse and is involved in regulating neurotransmitter release.
The team found lower levels of SV2A in the brains of schizophrenia patients, indicating a reduction of synapses. Certain areas exhibited significantly lower levels, such as the frontal cortex which coordinates use, recall and processing of memory, planning complex cognitive behaviour and personality expression. These findings were supported by the understanding that these areas are associated with some of the major cognitive impairments seen in schizophrenia, thus providing a potential clue that synaptic loss may underlie these problems.
But to test whether the loss was a result of the illness or in fact due to treatment, a preclinical study was conducted in rat models investigating the effect of antipsychotic drugs on the levels of SV2A. They found that the antipsychotics did not contribute to the synaptic loss seen in schizophrenic patients, thereby reinforcing their overall findings.
So, what does this mean for the development of schizophrenia treatment?
If the synaptic loss is an underlying key contributor in the disease, further research into the mechanisms could lead to exploring ways to prevent this loss. Moreover, since microglia, known as the immune cells of the brain, play a role in mediating synaptic pruning, there is also potential to target microglia and see if it could introduce a way of preventing excess synaptic loss; an investigation that the team have already begun.
“The human brain, with its approximately 100 trillion synapses, is an extraordinarily complex organ,” says Dr Ellis Chika Onwordi of the Psychiatric Imaging Group and first author of this study. “Having the means to characterise the distribution of these synapses in the living brain, and to find differences in synaptic distribution between patients with schizophrenia and healthy controls, represents a significant advance in our ability to study the neurobiology of schizophrenia.”
Professor Oliver Howes, who led the study, said: “Our current treatments for schizophrenia only target one aspect of the disease – the psychotic symptoms – but the debilitating cognitive symptoms, such as loss of abilities to plan and remember, often cause much more long-term disability and there’s no treatment for them at the moment. Synaptic loss is thought to underlie these symptoms.
“Our lab at the MRC London Institute of Medical Sciences is one of the few places in the world with this new tracer, which means we’ve been able for the first time to show there are lower levels of a synaptic protein in people with schizophrenia. This suggests that loss of synapses could underlie the development of schizophrenia.
“We need to develop new treatments for schizophrenia. This protein SV2A could be a target for new treatments to restore synaptic function.”
The people with schizophrenia who were scanned had all received antipsychotic medication, so the researchers wanted to exclude this as a factor in the synaptic dysfunction. They gave antipsychotic drugs, haloperidol and olanzapine, to rats for 28 days and found it did not affect the levels of the protein SV2A.
Professor Howes said: “This is reassuring as it’s suggesting that our antipsychotic treatments aren’t leading to loss of brain connections.
“Next we hope to scan younger people in the very early stages to see how synaptic levels change during the development of the illness and whether these changes are established early on or develop over time.”

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Health

Ambulance delays as heart attack victims left waiting one hour 57 minutes

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FREEDOM of Information requests reveal the worst ambulance delays out of 22 local authorities in Wales.

Postcode lottery revealed with patients in some areas waiting over double the amount of time for life-threatening calls

The average wait time for amber calls, which includes heart attack and stroke victims was 1 hour 57 minutes. In Swansea, it was 2 hours 33 minutes.

Shocking figures have unveiled the local areas in Wales with the longest ambulance delays, revealing a stark “postcode lottery” for response times to life-threatening calls.

Figures were provided by local authority giving a more local breakdown of the usual Health Board data.

Potential heart attack and stroke victims in the worst-hit areas are now waiting an average of one hour and 57 minutes for paramedics to arrive.

The figures, uncovered by the Liberal Democrats through Freedom of Information requests, reveal how patients whose lives are in immediate danger are waiting twice as long in some rural areas than urban ones. In Anglesey, patients waited an average of 12 minutes and 22 seconds for category 1 calls compared to 6 minutes 31 seconds in Newport.

However, the figures for amber calls painted a much starker picture with an average arrival time of 1 hour 57 minutes in Wales, with the worst in Swansea, where the average wait was 2 hours 33 minutes.

Overall, 13 out of the 22 local authorities in Wales had an average wait of over 2 hours for amber calls.

The Welsh Liberal Democrats are calling for action on the social care crisis in order to free up hospital beds and stop ambulances waiting outside hospitals.

Welsh Liberal Democrat Leader Jane Dodds MS said:

“These figures are heart-breaking, but not necessarily shocking to anyone who has had to call on an ambulance in recent months.

“Far too many people are being left to wait too long in an emergency across every region of Wales. The length of amber calls, which includes stroke and heart attack victims in particularly concerning.

“None of this is the fault of our hardworking ambulance staff who are doing their utmost in extremely difficult conditions.

“We must see an end to the postcode lottery in emergency care, it shouldn’t matter where you live, you should be able to get timely medical attention when you need it most.

“Every day we hear more and more devastating stories of pensioners left stranded for hours, or families watching a loved one die before a paramedic could reach them.

“This cannot continue, the Welsh Labour Government must bring forward extra support to get ambulance services through winter as well as a long-term strategy to ensure people can get emergency care when they need it. That means addressing workforce shortages, fixing the social care crisis and ending the shortage of hospital beds, all of which are leaving patients in ambulances stuck outside A&E for hours.”

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Bereavement books to support children at Bronglais Hospital

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THANKS to donations, Hywel Dda Health Charities has purchased a collection of children’s books on bereavement for the Meurig oncology ward at Bronglais Hospital.

The books help families to support children when there has been a terminal cancer diagnosis.

Ellen Masters, Meurig Ward Administrator, said: “By having these books on the ward we are able to guide and support children and young people dealing with bad news and bereavement.

“Using stories and activities can be a really good way to discuss issues with a child who has been bereaved, helping them to explore feelings and emotions around loss.

“Parents also appreciate having something they can read to children which deals sensitively with the issues.”

Pictured with some of the books is Senior Ward Sister Alaw Ciornei.

Nicola Llewelyn, Head of Hywel Dda Health Charities, the official charity of Hywel Dda University Health Board, said: “The support of our local communities enables us to provide services over and above what the NHS can provide in the three counties of Hywel Dda and we are extremely grateful for every donation we receive.”

For more details about the charity and how you can help support local NHS patients and staff, go to www.hywelddahealthcharities.org.uk

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NHS Dental Treatment in Wales Still 55% Lower Than Pre-Pandemic Levels

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RESPONDING to figures released this week showing that the number of courses of NHS dental treatment are still 55.1% lower than the year prior to the pandemic, the Welsh Liberal Democrats have reiterated their calls for the use of dental hygienists and dental nurses to be increased to help clear backlogs.

Overall, there was a decrease of 35.5% (539,959 patients) in the total number of patients treated, and the percentage of the total population treated decreased by 17.0 percentage points. This is the largest decrease for both adults and children since the series began in the 24-month period ending March 2006.

The figures also show a worrying decline in the number of children treated decreased with a reduction of 33.6% (125,246 patients).

Welsh Liberal Democrat Leader Jane Dodds MS told The Ceredigion Herald: “The figures we see today are very concerning. An inability to access an NHS dentist continues to be one of the main concerns I hear from my constituents.

“Just over the course of this summer, the largest town in Powys lost two out of four of its dental practices and the picture is similar across much of Wales.

“Everyone understands the challenges faced by dentistry following the pandemic. However, there are actions the Welsh Government can take both in the here and now and in the longer term to help clear backlogs and get NHS dentistry back on track.

“When I’ve spoken to industry experts over the summer they have all said the same thing, increasing the number of dental nurses and dental hygienists, as well as broadening the work they are allowed to do will help clear backlogs.

“I will continue to press Labour to make these changes as soon as possible.”

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