Posts tagged schizophrenia
Articles and news from the latest research reports.
Working memory hinders learning in schizophrenia
A new study pinpoints working memory as a source of learning difficulties in people with schizophrenia.
Working memory is known to be affected in the millions of people — about 1 percent of the population — who have schizophrenia, but it has been unclear whether that has a specific role in making learning more difficult, said Anne Collins, a postdoctoral researcher at Brown University and lead author of the study.
“We really tend to think of learning as a unitary, single process, but really it is not,” said Collins, who in 2012 along with co-author Michael Frank, associate professor of cognitive, linguistic, and psychological sciences, developed an experimental task and a computational model of cognition that can distinguish the contributions of working memory and reinforcement in the learning process. “We thought we could try to disentangle that here and see if the impairment was in both aspects, or only one of them.”
In the new study in the Journal of Neuroscience, cognitive scientists Collins and Frank collaborated with schizophrenia experts James Waltz and James Gold of the University of Maryland to measure the effects of working memory and reinforcement in learning by applying these methods. They found that only working memory was a source of impairment.
Learning about learning’s components
To find that out, they marshaled 49 volunteers with schizophrenia and an otherwise comparable set of 36 people without the condition to participate in the specially designed learning task. In each round, participants were shown a set of images and then were asked to push one of three buttons when they saw each image. With each button push they were told whether they had hit the correct button for that image. Over time, through trial and error, participants could learn which picture called for which button. With perfect memory, one wouldn’t need to see an image more than three times to learn the right button to push when it appeared.
The task explicitly involves employing the brain’s systems for working memory (keeping each image–button association in mind) and for reinforcement learning (wanting to repeat an action that led to the feedback of “correct” and to avoid one that produced “incorrect”). But in different rounds while the degree of reinforcement remained the same, the experimenters varied the number of images in the sets the volunteers saw, from two to six. What varied, therefore, was the degree to which working memory was taxed.
What the researchers found was that for both people with schizophrenia and for controls, the larger the image set size, the more trials it took to learn to press the correct button consistently for each image and the longer it took to react to each stimulus. People with schizophrenia generally performed worse on the task than healthy controls.
Those results show that as the task involved more images, it became harder to do – a matter of working memory, since the capacity to maintain information explicitly in memory is limited – but that alone did not prove that working memory was a source of learning problems for people with schizophrenia. They could also be doing worse because of a slower use of the reinforcement.
To determine that, the researchers used their computational models of how learning occurs in the brain to fit the experimental data. They asked what parameters in the models needed to vary to accurately predict the behavior they measured in people with and without schizophrenia.
That analysis revealed that varying parameters of working memory, such as capacity, but not parameters of reinforcement learning, accounted best for differences in behavior between the groups.
“With model-fitting techniques, I can look quantitatively, trial-by-trial and see that the model predicts subject’s choices,” she said. “The same model explains both the healthy group and the patient group, but with differences in parameters.”
That confirmed that working memory uniquely affected learning in people with schizophrenia, while reinforcement learning mechanisms did not, Collins said.
The study suggests that working memory could be a more important target than reinforcement learning among researchers and clinicians hoping to help improve learning for people with schizophrenia, Collins said.
Among mentally healthy people as well, the study illustrates that the different components of learning can be understood individually, even as they all interact in the brain to make learning happen.
“More broadly, it brings attention to the fact that we need to consider learning as a multiactor kind of behavior that can’t be just summarized by a single system,” Collins said. “It’s important to design tasks that can separate them out so we can extract different sources of variance and correctly match them to different neural systems.”
(Image: Shutterstock)
Blood test may help determine who is at risk for psychosis
A study led by University of North Carolina at Chapel Hill researchers represents an important step forward in the accurate diagnosis of people who are experiencing the earliest stages of psychosis.
Psychosis includes hallucinations or delusions that define the development of severe mental disorders such as schizophrenia. Schizophrenia emerges in late adolescence and early adulthood and affects about 1 in every 100 people. In severe cases, the impact on a young person can be a life compromised, and the burden on family members can be almost as severe.
The study published in the journal Schizophrenia Bulletin reports preliminary results showing that a blood test, when used in psychiatric patients experiencing symptoms that are considered to be indicators of a high risk for psychosis, identifies those who later went on to develop psychosis.
“The blood test included a selection of 15 measures of immune and hormonal system imbalances as well as evidence of oxidative stress,” said Diana O. Perkins, MD, MPH, professor of psychiatry in the UNC School of Medicine and corresponding author of the study. She is also medical director of UNC’s Outreach and Support Intervention Services (OASIS) program for schizophrenia.
“While further research is required before this blood test could be clinically available, these results provide evidence regarding the fundamental nature of schizophrenia, and point towards novel pathways that could be targets for preventative interventions,” Perkins said.
Clark D. Jeffries, PhD, bioinformatics scientist at the UNC-based Renaissance Computing Institute (RENCI), is a co-author of the study, which was conducted as part of the North American Prodrome Longitudinal Study (NAPLS), an international effort to understand risk factors and mechanisms for development of psychotic disorders.
“Modern, computer-based methods can readily discover seemingly clear patterns from nonsensical data,” said Jeffries. “Added to that, scientific results from studies of complex disorders like schizophrenia can be confounded by many hidden dependencies. Thus, stringent testing is necessary to build a useful classifier. We did that.”
The study concludes that the multiplex blood assay, if independently replicated and if integrated with studies of other classes of biomarkers, has the potential to be of high value in the clinical setting.
(Image: Shutterstock)
Size at birth affects risk of adolescent mental health disorders
New research from the Copenhagen Centre for Social Evolution and Yale University offers compelling support for the general evolutionary theory that birth weight and -length can partially predict the likelihood of being diagnosed with mental health disorders such as autism and schizophrenia later in life. The study analyzed medical records of 1.75 million Danish births, and subsequent hospital diagnoses for up to 30 years, and adjusted for almost all other known risk factors. The study is published today in the Proceedings of the Royal Society, London B.
The number of people diagnosed with mental health disorders is on the rise in most affluent countries, but we do not yet have a comprehensive understanding of the factors that make people vulnerable to these disorders.
A new analysis of the extensive Danish public health database suggests that part of the answer may reside in genetic imprints established at conception that influence both size at birth and mental health during childhood and early adolescence.
The study tests predictions of the evolutionary theory of genomic imprinting – the idea that during fetal development some genes inherited from the mother are expressed differently to those inherited from the father. The potential consequence of this asymmetry is that maternal and paternal genes in a fetus will not cooperate fully during this period, even though they subsequently have shared interests due to their lifetime commitment to the same body.
Opposite forces balance each other
The reason for the conflict is that some of the genes known to be expressed in the placenta and the brain carry imprints that affect resource provisioning of the unborn child. When such genes come from the father, they favor investment of more of the mother’s resources in the developing fetus, whereas the maternally-imprinted genes will normally compensate for such paternally-influenced manipulative effects to lessen the drain on maternal resources. These opposite forces balance each other in most pregnancies, with the result that most children are born with close to average length and weight and with a high likelihood of balanced mental health development.
Small deviations may well be favorable in human populations, when somewhat heavier babies are more likely to develop abstract talents and somewhat lighter babies above average social talents, for instance. However, this incurs the risk of increasing the frequency of autistic- and schizophrenic-spectrum disorders in the rare cases where imprinting imbalances are larger. The theory may explain why natural selection has not removed this portion of the burden of mental disease from our ancestors.
The new study tests these predictions and its results are remarkably consistent. They show that the change to the risk of developing mental disorders when born smaller or larger than average are relatively small, but very consistent, clearly diametrical, and part of the single continuum that the theory predicts.
“When we started this large scale analysis four years ago, we hoped to find evidence that genetic imprinting happens, but we did not expect that the results would match the predictions as consistently as we found”, explains Professor Jacobus Boomsma, Director of the Centre for Social Evolution, University of Copenhagen, who coordinated the work.
Boomsma adds: “Our study confirms that larger babies have a higher risk for incurring autism-spectrum diagnoses later in life and lower risk for schizophrenia-spectrum disorders. For example, Danish newborns are on average 52 cm long and being born at 54 cm increases the autism risk by 20%. However, these are relative risks and these disorders remain rare: in this example the absolute risk increases from 0.65% to 0.78%. Risk patterns are opposite in smaller newborns, who have higher risks for schizophrenia and lower risks for autism. Only for the smallest, prematurely-born babies does this diametric pattern disappear, because they have elevated risks for almost all disease categories”.
Evolutionary conflicts
Boomsma also underlines that focused genomic studies will be needed to find out which genes are involved and how they affect brain function: ”Our Centre’s main objective is to develop and test evolutionary theory about the ways in which gene-level conflicts can corrupt even the most sophisticated forms of naturally evolved cooperation. It is no surprise that humans are vulnerable to such deep evolutionary conflicts, as are other mammals, and it is both useful and interesting to be aware of this part of our biological heritage”, says Professor Boomsma.
(Source: science.ku.dk)
Brain Development in Schizophrenia Strays from the Normal Path
Schizophrenia is generally considered to be a disorder of brain development and it shares many risk factors, both genetic and environmental, with other neurodevelopmental disorders such as autism and intellectual disability.
The normal path for brain development is determined by the combined effects of a complex network of genes and a wide range of environmental factors.
However, longitudinal brain imaging studies in both healthy and patient populations are required in order to map the disturbances in brain structures as they emerge, i.e., the disturbed trajectories of brain development.
A new study by an international, collaborative group of researchers has measured neurodevelopment in schizophrenia, by studying brain development during childhood and adolescence in people with and without this disorder. With access to new statistical approaches and long-term follow-up with participants, in some cases over more than a decade, the researchers were able to describe brain development patterns associated with schizophrenia.
"Specifically, this paper shows that parts of the brain’s cortex develop differently in people with schizophrenia," said first author Dr. Aaron F. Alexander-Bloch, from the National Institute of Mental Health.
"The mapping of the path that the brain follows in deviating from normal development provides important clues to the underlying causes of the disorder," said Dr. John Krystal, Editor of Biological Psychiatry.
The findings were derived by investigating the trajectory of cortical thickness growth curves in 106 patients with childhood-onset schizophrenia and a comparison group of 102 healthy volunteers.
Each participant, ranging from 7–32 years of age, had repeated imaging scans over the course of several years. Then, using over 80,000 vertices across the cortex, the researchers modeled the effect of schizophrenia on the growth curve of cortical thickness.
This revealed differences that occur within a specific group of highly-connected brain regions that mature in synchrony during typical development, but follow altered trajectories of growth in schizophrenia.
"These findings show a relationship between the hypothesis that schizophrenia is a neurodevelopmental disorder and the longstanding hypothesis – first articulated by the German anatomist Karl Wernicke in the late 19th century – that it is a disease of altered connectivity between regions of the brain," added Alexander-Bloch.
This theoretical consistency is important, as it allows researchers to better focus future studies of brain connectivity in schizophrenia, by targeting the brain regions known to be affected.
Schizophrenia not a single disease but multiple genetically distinct disorders
New research shows that schizophrenia isn’t a single disease but a group of eight genetically distinct disorders, each with its own set of symptoms. The finding could be a first step toward improved diagnosis and treatment for the debilitating psychiatric illness.
The research at Washington University School of Medicine in St. Louis is reported online Sept. 15 in The American Journal of Psychiatry.
About 80 percent of the risk for schizophrenia is known to be inherited, but scientists have struggled to identify specific genes for the condition. Now, in a novel approach analyzing genetic influences on more than 4,000 people with schizophrenia, the research team has identified distinct gene clusters that contribute to eight different classes of schizophrenia.
“Genes don’t operate by themselves,” said C. Robert Cloninger, MD, PhD, one of the study’s senior investigators. “They function in concert much like an orchestra, and to understand how they’re working, you have to know not just who the members of the orchestra are but how they interact.”
Cloninger, the Wallace Renard Professor of Psychiatry and Genetics, and his colleagues matched precise DNA variations in people with and without schizophrenia to symptoms in individual patients. In all, the researchers analyzed nearly 700,000 sites within the genome where a single unit of DNA is changed, often referred to as a single nucleotide polymorphism (SNP). They looked at SNPs in 4,200 people with schizophrenia and 3,800 healthy controls, learning how individual genetic variations interacted with each other to produce the illness.
In some patients with hallucinations or delusions, for example, the researchers matched distinct genetic features to patients’ symptoms, demonstrating that specific genetic variations interacted to create a 95 percent certainty of schizophrenia. In another group, they found that disorganized speech and behavior were specifically associated with a set of DNA variations that carried a 100 percent risk of schizophrenia.
“What we’ve done here, after a decade of frustration in the field of psychiatric genetics, is identify the way genes interact with each other, how the ‘orchestra’ is either harmonious and leads to health, or disorganized in ways that lead to distinct classes of schizophrenia,” Cloninger said.
Although individual genes have only weak and inconsistent associations with schizophrenia, groups of interacting gene clusters create an extremely high and consistent risk of illness, on the order of 70 to 100 percent. That makes it almost impossible for people with those genetic variations to avoid the condition. In all, the researchers identified 42 clusters of genetic variations that dramatically increased the risk of schizophrenia.
“In the past, scientists had been looking for associations between individual genes and schizophrenia,” explained Dragan Svrakic, PhD, MD, a co-investigator and a professor of psychiatry at Washington University. “When one study would identify an association, no one else could replicate it. What was missing was the idea that these genes don’t act independently. They work in concert to disrupt the brain’s structure and function, and that results in the illness.”
Svrakic said it was only when the research team was able to organize the genetic variations and the patients’ symptoms into groups that they could see that particular clusters of DNA variations acted together to cause specific types of symptoms.
Then they divided patients according to the type and severity of their symptoms, such as different types of hallucinations or delusions, and other symptoms, such as lack of initiative, problems organizing thoughts or a lack of connection between emotions and thoughts. The results indicated that those symptom profiles describe eight qualitatively distinct disorders based on underlying genetic conditions.
The investigators also replicated their findings in two additional DNA databases of people with schizophrenia, an indicator that identifying the gene variations that are working together is a valid avenue to explore for improving diagnosis and treatment.
By identifying groups of genetic variations and matching them to symptoms in individual patients, it soon may be possible to target treatments to specific pathways that cause problems, according to co-investigator Igor Zwir, PhD, research associate in psychiatry at Washington University and associate professor in the Department of Computer Science and Artificial Intelligence at the University of Granada, Spain.
And Cloninger added it may be possible to use the same approach to better understand how genes work together to cause other common but complex disorders.
“People have been looking at genes to get a better handle on heart disease, hypertension and diabetes, and it’s been a real disappointment,” he said. “Most of the variability in the severity of disease has not been explained, but we were able to find that different sets of genetic variations were leading to distinct clinical syndromes. So I think this really could change the way people approach understanding the causes of complex diseases.”
(Source: news.wustl.edu)
Reassembling the Self by Susan Aldworth
Reassembling The Self started as a collaboration between artist Susan Aldworth and a team of neuroscientists and clinicians at the Institute of Neuroscience at Newcastle University, UK.
Centred in a study of the condition of schizophrenia, it weaves together art, science, psychiatry and individual histories in an extraordinary exploration of self, perception and the fragility of human identity.
Exhibition runs from 16 September until 11 October 2014
Difficulty assessing effort drives motivation deficits in schizophrenia
Individuals with schizophrenia often have trouble engaging in daily tasks or setting goals for themselves, and a new study from San Francisco State University suggests the reason might be their difficulty in assessing the amount of effort required to complete tasks.
The research, detailed in an article published this week in the Journal of Abnormal Psychology, can assist health professionals in countering motivation deficits among patients with schizophrenia and help those patients function normally by breaking up larger, complex tasks into smaller, easier-to-grasp ones.
"This is one of the first studies to carefully and systematically look at the daily activities of people with schizophrenia — what those people are doing, what goals are they setting for themselves," said David Gard, an associate professor of psychology at SF State who has spent years researching motivation and emotion. "We knew that people with schizophrenia were not engaging in a lot of goal-directed behavior. We just didn’t know why."
In 2011, Gard received a grant from the National Institute of Mental Health to study the reasons behind this difficulty in goal setting. An earlier article detailing other research from this study, published in May in the journal Schizophrenia Research, showed that when people with schizophrenia do set goals for themselves, they set them for the same reasons as persons without: to connect with others. But motivation deficits are still common among these individuals, and his latest study set out to pinpoint the reason.
Through a series of cognitive assessments and random phone calls, Gard and his colleagues at SF State and the University of California, San Francisco collected data from 47 people with and 41 people without schizophrenia. Participants were called four times a day, randomly throughout the day, for a week and asked about their current mood, as well as what they were doing; how much enjoyment they were getting out of it; and what their goals for the rest of the day were. The results were coded by variables such as how much pleasure they were getting out of their daily activities and how much effort was involved, then compared that with the results from the cognitive assessments.
Gard and his fellow researchers found that, while people with schizophrenia engage in low-impact, pleasurable goals — such as watching TV or eating food for enjoyment — as much as others, they have greater difficulty with more complex undertakings or goals requiring more effort.
"There’s something breaking down in the process around assessing high-effort, high-reward goals," Gard said. "When the reward is high and the effort is high, that’s when people with schizophrenia struggle to hold in mind and go after the thing that they want for themselves."
The findings indicate that health-care providers who want to help individuals with schizophrenia set goals for themselves should break larger tasks into smaller, simpler ones with small rewards. For example, instead of guiding a patient specifically toward the larger goal of getting in physical shape, a provider could instead encourage them to gradually walk a little bit more every day.
"That’s something we would do for everyone else, but it might have been avoided in patients with schizophrenia because we thought they weren’t experiencing as much pleasure from their activities as they actually are," Gard added. "We can help them to identify things that are pleasurable and reward them toward larger goals."
(Source: news.sfsu.edu)
Stuck in neutral: brain defect traps schizophrenics in twilight zone
People with schizophrenia struggle to turn goals into actions because brain structures governing desire and emotion are less active and fail to pass goal-directed messages to cortical regions affecting human decision-making, new research reveals.
Published in Biological Psychiatry, the finding by a University of Sydney research team is the first to illustrate the inability to initiate goal-directed behaviour common in people with schizophrenia.
The finding may explain why people with schizophrenia have difficulty achieving real-world goals such as making friends, completing education and finding employment.
"The apparent lack of motivation in schizophrenic patients isn’t because they lack goals or don’t enjoy rewards and pleasure," says the University of Sydney’s Dr Richard Morris, the study’s lead author.
"They enjoy as many experiences as other people, including food, movies and scenes of natural beauty.
"What appears to block them are specific brain deficits that prevent them from converting their desires and goals into choices and behaviour."
Using a control group research design, the researchers used a two-prong approach to reveal how and why schizophrenics fail to convert their preferences into congruent choices.
First, using a series of experiments involving choosing between different snack food rewards, experimenters revealed that:
- schizophrenic subjects had a liking for snack foods equivalent to healthy adults
- when researchers reduced the value of one of the snacks, both subjects and healthy adults subsequently preferred different snacks, as expected
- surprisingly, schizophrenic subjects had major difficulty choosing their preferred snack when provided with a choice between their preferred snack and the devalued snack.
Second, researchers used functional magnetic resonance imaging (fMRI) to measures brain activity while study subjects performed learning tasks involving snack foods.
This technique relies on the fact that cerebral blood flow and neuronal activity are coupled. When an area of the brain is in use, bloodflow to that region increases, thereby indicating neural activity. This neural activity can be presented graphically by colour-coding the strength of activation across the brain or in specific brain regions. The technique can localise neural activity to within millimetres.
Functional MRI results revealed the following:
- schizophrenic subjects had normal neural activity in the brain region responsible for decision-making (prefrontal cortex)
- among schizophrenic subjects, brain regions responsible, in part, for controlling actions and choice (the caudate) had far lower neural activity than in healthy subjects
- lower neural activity in the caudate regions was correlated with the difficulty that schizophrenic subjects’ had applying their food preferences to obtain future snack foods.
"Pathology in the caudate and associated brain regions may prevent schizophrenic subjects from properly evaluating their desires then transmitting that information to guide their behavior," says Dr Morris.
"This means that desires and goals are intact in people with schizophrenia, however they have difficulty choosing the right course of action to achieve those goals.
"This failure to integrate desire with action means people with schizophrenia are stuck in limbo, wanting a normal life but unable to take the necessary steps to achieve it."
Schizophrenia affects one per cent of people worldwide, including in Australia.
However so-called “poor motivation” in schizophrenia is a major economic concern because it is not treated by current medicines, and often means patients fail to finish their education or hold a full-time job.
(Source: sydney.edu.au)
Schizophrenia’s genetic skyline rising
The largest genomic dragnet of any psychiatric disorder to date has unmasked 108 chromosomal sites harboring inherited variations in the genetic code linked to schizophrenia, 83 of which had not been previously reported. By contrast, the “skyline” of such suspect variants associated with the disorder contained only 5 significant peaks in 2011. By combining data from all available schizophrenia genetic samples, researchers supported by the National Institutes of Health powered the search for clues to the molecular basis of the disorder to a new level.
“While the suspect variation identified so far only explains only about 3.5 percent of the risk for schizophrenia, these results warrant exploring whether using such data to calculate an individual’s risk for developing the disorder might someday be useful in screening for preventive interventions,” explained Thomas R. Insel, M.D., director of the NIH’s National Institute of Mental Health, one funder of the study. “Even based on these early predictors, people who score in the top 10 percent of risk may be up to 20-fold more prone to developing schizophrenia.”
The newfound genomic signals are not simply random sites of variation, say the researchers. They converge around pathways underlying the workings of processes involved in the disorder, such as communication between brain cells, learning and memory, cellular ion channels, immune function and a key medication target.
The Schizophrenia Working Group of the Psychiatric Genomic Consortium (PGC) reports on its genome-wide analysis of nearly 37,000 cases and more than 113,000 controls in the journal Nature, July 21, 2014. The NIMH-supported PGC represents more than 500 investigators at more than 80 research institutions in 25 countries.
Prior to the new study, schizophrenia genome-wide studies had identified only about 30 common gene variants associated with the disorder. Sample sizes in these studies were individually too small to detect many of the subtle effects on risk exerted by such widely shared versions of genes. The PGC investigators sought to maximize statistical power by re-analyzing not just published results, but all available raw data, published and unpublished. Their findings of 108 illness-associated genomic locations were winnowed from an initial pool of about 9.5 million variants.
A comparison of the combined study data with findings in an independent sample of cases and controls suggest that considerably more such associations of this type are likely to be uncovered with larger sample sizes, say the researchers.
There was an association confirmed with variation in the gene that codes for a receptor for the brain chemical messenger dopamine, which is known to be the target for antipsychotic medications used to treat schizophrenia. Yet evidence from the study supports the view that most variants associated with schizophrenia appear to exert their effects via the turning on and off of genes rather than through coding for proteins.
The study found a notable overlap between protein-related functions of some linked common variants and rare variants associated with schizophrenia in other studies. These included genes involved in communication between neurons via the chemical messenger glutamate, learning and memory, and the machinery controlling the influx of calcium into cells.
“The overlap strongly suggests that common and rare variant studies are complementary rather than antagonistic, and that mechanistic studies driven by rare genetic variation will be informative for schizophrenia,” say the researchers.
Among the strongest associations detected, as in in previous genome-wide genetic studies, was for variation in tissues involved in immune system function. Although the significance of this connection for the illness process remains a mystery, epidemiologic evidence has long hinted at possible immune system involvement in schizophrenia.
Findings confirm that it’s possible to develop risk profile scores based on schizophrenia-associated variants that may be useful in research – but for now aren’t ready to be used clinically as a predictive test, say the researchers.
They also note that the associated variations detected in the study may not themselves be the source of risk for schizophrenia. Rather, they may be signals indicating the presence of disease-causing variation nearby in a chromosomal region.
Researchers are following up with studies designed to pinpoint the specific sequences and genes that confer risk. The PGC is also typing genes in hundreds of thousands of people worldwide to enlarge the sample size, in hopes of detecting more genetic variation associated with mental disorders. Successful integration of data from several GWAS studies suggests that this approach would likely be transferrable to similar studies of other disorders, say the researchers.
“These results underscore that genetic programming affects the brain in tiny, incremental ways that can increase the risk for developing schizophrenia,” said Thomas Lehner, Ph.D., chief of NIMH’s Genomics Research Branch. “They also validate the strategy of examining both common and rare variation to understand this complex disorder.”
Antipsychotic drugs linked to slight decrease in brain volume
A study published today 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.
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.”