Posts tagged schizophrenia
Articles and news from the latest research reports.
Tickling the Brain with Magnetic Stimulation Improves Memory in Schizophrenia
Cognitive impairments are disabling for individuals with schizophrenia, and no satisfactory treatments currently exist. These impairments affect a wide range of cognition, including memory, attention, verbal and motor skills, and IQ. They appear in the earliest stages of the disease and disrupt or even prevent normal day-to-day functioning.
Scientists are exploring a variety of strategies to reduce these impairments including “exercising the brain” with specially designed computer games and medications that might improve the function of brain circuits.
In this issue of Biological Psychiatry, Dr. Mera Barr and her colleagues at University of Toronto provide new evidence that stimulating the brain using repetitive transcranial magnetic stimulation (rTMS) may be an effective strategy to improve cognitive function.
“In a randomized controlled trial, we evaluated whether rTMS can improve working memory in schizophrenia,” said Barr and senior author Dr. Zafiris Daskalakis. “Our results showed that rTMS resulted in a significant improvement in working memory performance relative to baseline.”
Transcranial magnetic stimulation is a non-invasive procedure that uses magnetic fields to stimulate nerve cells. It does not require sedation or anesthesia and so patients remain awake, reclined in a chair, while treatment is administered through coils placed near the forehead.
“TMS can have lasting effects on brain circuit function because this approach not only changes the activity of the circuit that is being stimulated, but it also may change the plasticity of that circuit, i.e., the capacity of the circuit to remodel itself functionally and structurally to support cognitive functions,” explained Dr. John Krystal, Editor of Biological Psychiatry.
Previous work has shown that rTMS improves working memory in healthy individuals and a recent open-label trial showed promising findings for verbal memory in schizophrenia patients. This series of findings led this study to determine if high frequency rTMS could improve memory in individuals with schizophrenia.
They recruited medicated schizophrenia patients who completed a working memory task before and after 4 weeks of treatment. Importantly, this was a double-blind study, where neither the patients nor the researchers knew who was receiving real rTMS or a sham treatment that was designed to entirely mimic the procedure without actually delivering brain stimulation.
rTMS not only improved working memory in patients after 4 weeks, but the improvement was to a level comparable to healthy subjects. These findings suggest that rTMS may be a novel, efficacious, and safe treatment for working memory deficits in schizophrenia.
In 2008, rTMS was FDA-approved to treat depression for individuals who don’t respond to pharmacotherapy. The hope is that additional research will replicate these findings and finally provide an approved treatment for cognitive impairments in schizophrenia.
The authors concluded: “Working memory is an important predictor of functional outcome. Developing novel treatments aimed at improving these deficits may ultimately translate into meaningful changes in the lives of patients suffering from this debilitating disorder.”
(Source: elsevier.com)
Virus and genes involved in causation of schizophrenia
For the first time, an international team of researchers has found that a combination of a particular virus in the mother and a specific gene variant in the child increases the risk of the child developing schizophrenia.
Viruses and genes interact in a way that may increase the risk of developing schizophrenia significantly. This happens already in the developing foetus.
An international team of scientists led by Aarhus University, Denmark, has made this discovery. As the first in the world, they scanned the entire genome of hundreds of sick and healthy people to see if there is an interaction between genes and a very common virus - cytomegalovirus - and to see whether the interaction influences the risk of developing schizophrenia.
And it does.
Women that have been infected by the virus - and around 70% has - will have a statistically significant increased risk of giving birth to a child who later develops schizophrenia if the child also has the aforementioned gene variant. This variant is found in 15 percent. The risk is five times higher than usual, the researchers report in Molecular Psychiatry.
No cause for alarm
People infected with cytomegalovirus most often do not know it, as the infection by the virus, which belongs to the herpes virus family, is usually very mild. But the researchers stress that there is no cause for alarm - even if both risk factors are present in mother and child, there may be a variety of other factors that prevents disease development in the child.
But as schizophrenia affects 1 per cent of the global population, this new knowledge is very important.
"In the longer term, the development of an effective vaccine against cytomegalovirus may help to prevent many cases of schizophrenia," says Professor of Medical Genetics at Aarhus University, Anders Børglum.
"And our discovery emphasizes that mental disorders such as schizophrenia may arise in the context of an interaction between genes and biological environmental factors very early in life."
(Source: eurekalert.org)
Single gene might explain dramatic differences among people with schizophrenia
Some of the dramatic differences seen among patients with schizophrenia may be explained by a single gene that regulates a group of other schizophrenia risk genes. These findings appear in a new imaging-genetics study from the Centre for Addiction and Mental Health (CAMH).
The study revealed that people with schizophrenia who had a particular version of the microRNA-137 gene (or MIR137), tended to develop the illness at a younger age and had distinct brain features – both associated with poorer outcomes – compared to patients who did not have this version. This work, led by Drs. Aristotle Voineskos and James Kennedy, appears in the latest issue of Molecular Psychiatry.
Treating schizophrenia is particularly challenging as the illness can vary from patient to patient. Some individuals stay hospitalized for years, while others respond well to treatment.
"What’s exciting about this study is that we could have a legitimate answer as to why some of these differences occur," explained Dr. Voineskos, a clinician-scientist in CAMH’s Campbell Family Mental Health Research Institute. "In the future, we might have the capability of using this gene to tell us about prognosis and how a person might respond to treatment."
"Drs. Voineskos and Kennedy’s findings are very important as they provide new insights into the genetic bases of this condition that affects thousands of Canadians and their families," said Dr. Anthony Phillips, Scientific Director at the Canadian Institutes of Health Research Institute of Neurosciences, Mental Health and Addiction.
Also, until now, sex has been the strongest predictor of the age at which schizophrenia develops in individuals. Typically, women tend to develop the illness a few years later than men, and experience a milder form of the disease.
"We showed that this gene has a bigger effect on age-at-onset than one’s gender has," said Dr. Voineskos, who heads the Kimel Family Translational Imaging-Genetics Research Laboratory at CAMH. "This may be a paradigm shift for the field."
The researchers studied MIR137 — a gene involved in turning on and off other schizophrenia-related genes — in 510 individuals living with schizophrenia. The scientists found that patients with a specific version of the gene tended to develop the illness at a younger age, around 20.8 years of age, compared to 23.4 years of age among those without this version.
"Although three years of difference in age-at-onset may not seem large, those years are important in the final development of brain circuits in the young adult," said Dr. Kennedy, Director of CAMH’s Neuroscience Research Department. "This can have major impact on disease outcome."
In a separate part of the study involving 213 people, the researchers used MRI and diffusion tensor-magnetic resonance brain imaging (DT-MRI). They found that individuals who had the particular gene version tended to have unique brain features. These features included a smaller hippocampus, which is a brain structure involved in memory, and larger lateral ventricles, which are fluid-filled structures associated with disease outcome. As well, these patients tended to have more impairment in white matter tracts, which are structures connecting brain regions, and serving as the information highways of the brain.
Developing tests that screen for versions of this gene could be helpful in treating patients earlier and more effectively.
"We’re hoping that in the near future we can use this combination of genetics and brain imaging to predict how severe a version of illness someone might have," said Dr. Voineskos. "This would allow us to plan earlier for specific treatments and clinical service delivery and pursue more personalized treatment options right from the start."
(Image: Akelei van Dam)
Malign environmental combination favours schizophrenia
The interplay between an infection during pregnancy and stress in puberty plays a key role in the development of schizophrenia, as behaviourists from ETH Zurich demonstrate in a mouse model. However, there is no need to panic.
Around one per cent of the population suffers from schizophrenia, a serious mental disorder that usually does not develop until adulthood and is incurable. Psychiatrists and neuroscientists have long suspected that adverse enviromental factors may play an important role in the development of schizophrenia. Prenatal infections such as toxoplasmosis or influenza, psychological, stress or family history have all come into question as risk factors. Nevertheless, until now researchers were unable to identify the interplay of the individual factors linked to this serious mental disease.
However, a research group headed by Urs Meyer, a senior scientist at the Laboratory of Physiology & Behaviour at ETH Zurich, has now made a breakthrough: for the first time, they were able to find clear evidence that the combination of two environmental factors contributes significantly to the development of schizophrenia-relevant brain changes and at which stages in a person’s life they need to come into play for the disorder to break out. The researchers developed a special mouse model, with which they were able to simulate the processes in humans virtually in fast forward. The study has just been published in the journal Science.
IQ loss linked to Schizophrenia genes
People at greater genetic risk of schizophrenia could see a fall in IQ as they age, study shows.
Scientists at the University say IQ decline in those at risk could happen even if they do not develop schizophrenia.
The findings could lead to new research into how different genes for schizophrenia affect brain function over time. Schizophrenia - a severe mental disorder characterised by delusions and by hallucinations - is in part caused by genetic factors.
The researchers used the latest genetic analysis techniques to reach their conclusion on how thinking skills change with age.
Retaining our thinking skills as we grow older is important for living well and independently. If nature has loaded a person’s genes towards schizophrenia, then there is a slight but detectable worsening in cognitive functions between childhood and old age. -Professor Ian Deary (Director of the University of Edinburgh’s Centre for Cognitive Ageing and Cognitive Epidemiology)
Historical data
They compared the IQ scores of more than 1,000 people from Edinburgh.
The people were tested for general cognitive functions in 1947, aged 11, and again when they were around 70 years old.
The researchers were able to examine people’s genes and calculate each subject’s genetic likelihood of developing schizophrenia, even though none of the group had ever developed the illness.
They then compared the IQ scores of people with a high and low risk of developing schizophrenia.
Scientists found that there was no difference at age 11, but people with a greater genetic risk of schizophrenia had slightly lower IQs at age 70.
Those people who had more genes linked to schizophrenia also had a greater estimated fall in IQ over their lifetime than those at lower risk.
Cognitive impact
With further research into how these genes affect the brain, it could become possible to understand how genes linked to schizophrenia affect people’s cognitive functions as they age. -Professor Andrew McIntosh (Centre for Clinical Brain Sciences)
Schizophrenia affects around 1 per cent of the population, often in the teenage or early adult years, and is associated with problems in mental ability and memory.
The study, which was funded by the BBSRC, Age UK, and the Chief Scientist Office, is published in the journal Biological Psychiatry.
Eye movements reveal impaired reading in schizophrenia
A study of eye movements in schizophrenia patients provides new evidence of impaired reading fluency in individuals with the mental illness.
The findings, by researchers at McGill University in Montreal, could open avenues to earlier detection and intervention for people with the illness.
While schizophrenia patients are known to have abnormalities in language and in eye movements, until recently reading ability was believed to be unaffected. That is because most previous studies examined reading in schizophrenia using single-word reading tests, the McGill researchers conclude. Such tests aren’t sensitive to problems in reading fluency, which is affected by the context in which words appear and by eye movements that shift attention from one word to the next.
The McGill study, led by Ph.D. candidate Veronica Whitford and psychology professors Debra Titone and Gillian A. O’Driscoll, monitored how people move their eyes as they read simple sentences. The results, which were first published online last year, appear in the February issue of the Journal of Experimental Psychology: General.
Eye movement measures provide clear and objective indicators of how hard people are working as they read. For example, when struggling with a difficult sentence, people generally make smaller eye movements, spend more time looking at each word, and spend more time re-reading words. They also have more difficulty attending to upcoming words, so they plan their eye movements less efficiently.
The McGill study, which involved 20 schizophrenia outpatients and 16 non-psychiatric participants, showed that reading patterns in people with schizophrenia differed in several important ways from healthy participants matched for gender, age, and family social status. People with schizophrenia read more slowly, generated smaller eye movements, spent more time processing individual words, and spent more time re-reading. In addition, people with schizophrenia were less efficient at processing upcoming words to facilitate reading.
The researchers evaluated factors that could contribute to the problems in reading fluency among the schizophrenia outpatients – specifically, their ability to parse words into sound components and their ability to skillfully control eye movements in non-reading contexts. Both factors were found to contribute to the reading deficits.
Genes for autism and schizophrenia only active in developing brains
Genes linked to autism and schizophrenia are only switched on during the early stages of brain development, according to a collaboration between researchers at Imperial College London, the University of Oxford and King’s College London.
This new study adds to the evidence that autism and schizophrenia are neurodevelopmental disorders, a term describing conditions that originate during early brain development.
The researchers studied gene expression in the brains of mice throughout their development, from 15-day old embryos to adults, and their results are published in Proceedings of the National Academy of Sciences.
The research focused on cells in the ‘subplate’, a region of the brain where the first neurons (nerve cells) develop. Subplate neurons are essential to brain development, and provide the earliest connections within the brain.
'The subplate provides the scaffolding required for a brain to grow, so is important to consider when studying brain development,' says Professor Zoltán Molnár, senior author of the paper from the University of Oxford, 'Looking at the pyramids in Egypt today doesn't tell us how they were actually built. Studying adult brains is like looking at the pyramids today, but by studying the developing brains we are able to see the transient scaffolding that has been used to construct it.'
The study shows that certain genes linked to autism and schizophrenia are only active in the subplate during specific stages of development. The data analysis was designed by Dr Enrico Petretto, Senior Lecturer in Genomic Medicine at Imperial College London. Dr Petretto said: “We looked at the full network of genes in the brain to identify which pathways play a role in early brain development. This allowed us to find coherent clusters of genes previously associated with susceptibility to autism spectrum disorders or schizophrenia. These results provide a unique resource for our understanding of how gene behaviour changes in the mouse subplate from the early embryonic stage to adulthood. This means we are better equipped to investigate how the gene network changes in the developing brain and identify any links with neurodevelopmental disorders.”
The team was able to map gene activity in full detail thanks to these new methods which allowed them to dissect and profile gene expression from small numbers of cells. This also enabled them to identify the different populations of subplate neurons more accurately.
Professor Hugh Perry, chair of the Medical Research Council’s Neuroscience and Mental Health Board, said: “By being able to pinpoint common genetic factors for neurological conditions such as autism and schizophrenia, scientists are able to understand an important part of the story as to why things go awry as our brains develop. The Medical Research Council’s commitment to a broad portfolio of neuroscience and mental health research places us in a unique position to respond to the challenge of mental ill health and its relationship with physical health and wellbeing.”
(Source: www3.imperial.ac.uk)
Brain activity study lends insight into schizophrenia
Magnetic fields produced by the naturally occurring electrical currents in the brain could potentially be used as an objective test for schizophrenia and help to better understand the disease, according to new research published today.
A team of researchers from Plymouth and Spain have used the non-invasive magnetoencephalogram (MEG) technique to find two spectral features that are significantly different in schizophrenia patients compared to healthy control subjects.
Furthermore, they found that there were four spectral features in the brain signals of schizophrenia patients that changed with age compared to healthy control subjects, suggesting that schizophrenia affects the way in which brain activity evolves with age.
The study has been published today, Thursday 31 January, in the journal Physiological Measurement.
Schizophrenia is a serious psychiatric disorder, usually starting in late adolescence, which is characterised by a range of positive and negative symptoms, including hallucinations, delusions, paranoia, cognitive impairment, social withdrawal, self-neglect and loss of motivation and initiative.
It has no objective test and is currently diagnosed by clinicians who assess patients using a defined set of criteria.
Lead author of the study Dr Javier Escudero said: “At present, there is no blood, cerebrospinal fluid, brain imaging or neurophysiological test for schizophrenia in routine clinical practice. The diagnosis relies on the interpretation of symptoms and clinical history according to consensus criteria.
"The advent of an objective marker for schizophrenia would significantly facilitate the diagnosis and offer a better understanding of the neurobiological basis of the disease."
In this study, the frequency spectrum of the MEG background activity was analysed in 15 schizophrenia patients with positive symptoms and 17 age-matched healthy control subjects.
A range of spectral features from the MEGs were analysed to provide a holistic view of the brain activity of each subject. The MEG produced 148 values for each subject, which were subsequently divided into five different groups representing different parts of the brain, and were statistically analysed.
The researchers also investigated whether the spectral features could be used to distinguish between schizophrenia patients and the healthy controls. They showed that they were able to classify patients with 71 per cent accuracy.
"The long-term vision is to develop a low-cost, non-invasive and objective test to aid the diagnosis of this and other brain diseases. The magnetoencephalogram is able to provide very detailed information about the brain activity; however, it is expensive. Therefore, we aim to transfer these developments to electroencephalogram recordings in the future, as this technique meets those requirements of reduced cost, high availability and non-invasiveness," continued Dr Escudero.
(Image: Shutterstock)
Protein Family Linked to Autism Suppresses the Development of Inhibitory Synapses
Synapse development is promoted by a variety of cell adhesion molecules that connect neurons and organize synaptic proteins. Many of these adhesion molecules are linked to neurodevelopmental disorders; mutations in neuroligin and neurexin proteins, for example, are associated with autism and schizophrenia. According to a study in The Journal of Cell Biology, another family of proteins linked to these disorders regulates the function of neuroligins and neurexins in order to suppress the development of inhibitory synapses.
Like neurexins and neuroligins, the neuronal proteins MDGA1 and MDGA2 have been linked to autism and schizophrenia, but their function in neurodevelopment was unknown. Both MDGA proteins localize to the plasma membrane, and their extracellular domains are similar to those of cell adhesion molecules. On the other hand, postsynaptic neuroligin proteins are known to help synapses form by associating with neurexins on presynaptic membranes. Neuroligin-2 specifically boosts the development of inhibitory synapses, whereas neuroligin-1 promotes the development of excitatory synapses.
Ann Marie Craig and colleagues from the University of British Columbia investigated the function of MDGAs using co-culture assays, in which postsynaptic proteins like neuroligin-1 or -2 are expressed in non-neuronal cells and then tested for their ability to induce presynaptic differentiation in neighboring neurons. MDGA1 didn’t promote synapse formation in these assays. Instead, it inhibited the ability of neuroligin-2 to promote synapse development. The researchers found that MDGA1’s extracellular domains bound to neuroligin-2, blocking its association with neurexin. The same domains were sufficient to inhibit neuroligin-2’s synapse-promoting activity. In contrast, MDGA1 didn’t show high affinity binding to, or inhibit the function of, neuroligin-1. This suggested that, by inhibiting neuroligin-2, MDGA1 might specifically suppress the development of inhibitory synapses, so Craig and colleagues investigated MDGA1 function in cultured hippocampal neurons.
“Overexpressing MDGA1 in neurons reduced the density of inhibitory synapses without affecting excitatory synapses,” Craig says. Knocking down MDGA1, on the other hand, increased inhibitory synapse development but had no effect on excitatory synapses.
“I can’t think of any other proteins that specifically suppress inhibitory synapse formation,” says Craig. Indeed, very few proteins in general have been identified as negative regulators of synapse development, compared to the many proteins that are known to promote synaptogenesis. The results suggest that function-altering mutations in the MDGA proteins may disrupt the balance of excitatory and inhibitory synapses in the brain, potentially explaining the development of autism and other neurodevelopmental disorders.
“This puts MDGAs in the same pathway as neurexins and neuroligins and strengthens the evidence for the involvement of synaptic organizing proteins in autism and schizophrenia,” Craig explains. As well as investigating the function of MDGA2, the researchers want to explore the therapeutic potential of MDGA1 inhibitors, not only against autism and schizophrenia but also for the treatment of epilepsy, in which excitatory and inhibitory synapses are also imbalanced.
(Source)
Evidence Mounts for Role of Mutated Genes in Development of Schizophrenia
Johns Hopkins researchers have identified a rare gene mutation in a single family with a high rate of schizophrenia, adding to evidence that abnormal genes play a role in the development of the disease.
The researchers, in a report published in the journal Molecular Psychiatry, say that family members with the mutation in the gene Neuronal PAS domain protein 3 (NPAS3) appear at high risk of developing schizophrenia or another debilitating mental illnesses.
Normally functioning NPAS3 regulates the development of healthy neurons, especially in a region of the brain known as the hippocampus, which appears to be affected in schizophrenia. The Johns Hopkins researchers say they have evidence that the mutation found in the family may lead to abnormal activity of NPAS3, which has implications for brain development and function.
"Understanding the molecular and biological pathways of schizophrenia is a powerful way to advance the development of treatments that have fewer side effects and work better than the treatments now available," says study leader Frederick C. Nucifora Jr., Ph.D., D.O., M.H.S., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. "We could definitely use better medicines."