Posts tagged schizophrenia
Articles and news from the latest research reports.
New genetic mutations shed light on schizophrenia
Researchers from the Broad Institute and several partnering institutions have taken a closer look at the human genome to learn more about the genetic underpinnings of schizophrenia. In two studies published this week in Nature (1, 2), scientists analyzed the exomes, or protein-coding regions, of people with schizophrenia and their healthy counterparts, pinpointing the sites of mutations and identifying patterns that reveal clues about the biology underlying the disorder.
Toward a Molecular Explanation for Schizophrenia
Surprisingly little is known about schizophrenia. It was only recognized as a medical condition in the past few decades, and its exact causes remain unclear. Since there is no objective test for schizophrenia, its diagnosis is based on an assortment of reported symptoms. The standard treatment, antipsychotic medication, works less than half the time and becomes increasingly ineffective over time.
Now, Prof. Illana Gozes — the Lily and Avraham Gildor Chair for the Investigation of Growth Factors, the director of the Adams Super Center for Brain Studies at the Sackler Faculty of Medicine, and a member of the Sagol School of Neuroscience at Tel Aviv University — has discovered that an important cell-maintenance process called autophagy is reduced in the brains of schizophrenic patients. The findings, published in Nature’s Molecular Psychiatry, advance the understanding of schizophrenia and could enable the development of new diagnostic tests and drug treatments for the disease.
"We discovered a new pathway that plays a part in schizophrenia," said Prof. Gozes. "By identifying and targeting the proteins known to be involved in the pathway, we may be able to diagnose and treat the disease in new and more effective ways."
Graduate students Avia Merenlender-Wagner, Anna Malishkevich, and Zeev Shemer of TAU, Prof. Brian Dean and colleagues of the University of Melbourne, and Prof. Galila Agam and Joseph Levine of Ben Gurion University of the Negev and Beer Sheva’s Psychiatry Research Center and Mental Health Center collaborated on the research.
Mopping up
Autophagy is like the cell’s housekeeping service, cleaning up unnecessary and dysfunctional cellular components. The process — in which a membrane engulfs and consumes the clutter — is essential to maintaining cellular health. But when autophagy is blocked, it can lead to cell death. Several studies have tentatively linked blocked autophagy to the death of brain cells seen in Alzheimer’s disease.
Brain-cell death also occurs in schizophrenics, so Prof. Gozes and her colleagues set out to see if blocked autophagy could be involved in the progression of that condition as well. They found RNA evidence of decreased levels of the protein beclin 1 in the hippocampus of schizophrenia patients, a brain region central to learning and memory. Beclin 1 is central to initiating autophagy — its deficit suggests that the process is indeed blocked in schizophrenia patients. Developing drugs to boost beclin 1 levels and restart autophagy could offer a new way to treat schizophrenia, the researchers say.
"It is all about balance," said Prof Gozes. "Paucity in beclin 1 may lead to decreased autophagy and enhanced cell death. Our research suggests that normalizing beclin 1 levels in schizophrenia patients could restore balance and prevent harmful brain-cell death."
Next, the researchers looked at protein levels in the blood of schizophrenia patients. They found no difference in beclin 1 levels, suggesting that the deficit is limited to the hippocampus. But the researchers also found increased levels of another protein, activity-dependent neuroprotective protein (ADNP), discovered by Prof. Gozes and shown to be essential for brain formation and function, in the patients’ white blood cells. Previous studies have shown that ADNP is also deregulated in the brains of schizophrenia patients.
The researchers think the body may boost ADNP levels to protect the brain when beclin 1 levels fall and autophagy is derailed. ADNP, then, could potentially serve as a biomarker, allowing schizophrenia to be diagnosed with a simple blood test.
An illuminating discovery
To further explore the involvement of ADNP in autophagy, the researchers ran a biochemical test on the brains of mice. The test showed that ADNP interacts with LC3, another key protein regulating autophagy — an interaction predicted by previous studies. In light of the newfound correlation between autophagy and schizophrenia, they believe that this interaction may constitute part of the mechanism by which ADNP protects the brain.
Prof. Gozes discovered ADNP in 1999 and carved a protein fragment, NAP, from it. NAP mimics the protein nerve cell protecting properties. In follow-up studies Prof. Gozes helped develop the drug candidate davunetide (NAP). In Phase II clinical trials, davunetide (NAP) improved the ability of schizophrenic patients to cope with daily life. A recent collaborative effort by Prof. Gozes and Dr. Sandra Cardoso and Dr. Raquel Esteves showed that NAP improved autophagy in cultures of brain-like cells. The current study further shows that NAP facilitates the interaction of ADNP and LC3, possibly accounting for NAP’s results in schizophrenia patients. The researchers hope NAP will be just the first of their many discoveries to improve understanding and treatment of schizophrenia.
(Image: Shutterstock)
The pauses that refresh the memory
Certain symptoms of schizophrenia may arise from uncontrolled activation of neurons that help to build memories during periods of rest
Sufferers of schizophrenia experience a broad gamut of symptoms, including hallucinations and delusions as well as disorientation and problems with learning and memory. This diversity of neurological deficits has made schizophrenia extremely difficult for scientists to understand, thwarting the development of effective treatments. A research team led by Susumu Tonegawa from the RIKEN–MIT Center for Neural Circuit Genetics has now revealed disruptions in the activity of particular clusters of neurons that might account for certain core symptoms of this disorder.
Tonegawa’s laboratory previously found that mice lacking the protein calcineurin in certain regions of the brain exhibit many behavioral deficits that are characteristic of schizophrenia. In their most recent study, the researchers sought out physiological alterations at the single-cell or circuit level that could connect the absence of the calcineurin protein in the brain with these behavioral impairments.
Their study focused on the hippocampus, a region of the brain associated with memory and spatial learning. Within the hippocampus, specialized ‘place cells’ switch on and off as an animal explores its environment. During subsequent periods of wakeful rest, these place cells continue to fire in patterns that essentially ‘replay’ recent wanderings, allowing the brain to build memories based on these experiences. The researchers used precisely positioned electrodes to measure differences in brain activity in these cells for normal mice and the calcineurin-deficient mouse model of schizophrenia.
Remarkably, essentially identical place-cell activity patterns were observed for both sets of mice during active exploration. Once the animals were at rest, however, the calcineurin-deficient mice displayed a dramatic increase in place-cell activity. In the normal hippocampus, the resting replay process depended on sequential activity from place cells corresponding to specific, real-world spatial coordinates. In contrast, this correlation was all but lost in the calcineurin-deficient mice. Instead, these neurons often seemed to fire indiscriminately, creating high levels of ‘noise’ that overwhelmed actual location information and thwarted memory formation.
“Our study provides the first potential evidence of disorganized thinking processes in a schizophrenia model at the single-cell and circuit level,” says Junghyup Suh, a member of Tonegawa’s research team. These findings fit with an emerging model that suggests that schizophrenic symptoms may arise from excess activation of brain regions within a ‘default mode network’—which includes the hippocampus—during wakeful rest. “Neurobiological approaches that can calm down the default mode network may therefore open up new avenues to alleviating symptoms or curing this mental disorder,” says Suh.
Scientists identify protein responsible for controlling communication between brain cells
Scientists are a step closer to understanding how some of the brain’s 100 billion nerve cells co-ordinate their communication. The study is published in the journal Cell Reports.
The University of Bristol research team investigated some of the chemical processes that underpin how brain cells co-ordinate their communication. Defects in this communication are associated with disorders such as epilepsy, autism and schizophrenia, and therefore these findings could lead to the development of novel neurological therapies.
Neurons in the brain communicate with each other using chemicals called neurotransmitters. This release of neurotransmitter from neurons is tightly controlled by many different proteins inside the neuron. These proteins interact with each other to ensure that neurotransmitter is only released when necessary. Although the mechanisms that control this release have been extensively studied, the processes that co-ordinate how and when the component proteins interact is not fully understood.
The School of Biochemistry researchers have now discovered that one of these proteins called ‘RIM1α’ is modified by a small protein named ‘SUMO’ which attaches to a specific region in RIM1α. This process acts as a ‘molecular switch’ which is required for normal neurotransmitter release.
Jeremy Henley, Professor of Molecular Neuroscience in the University’s Faculty of Medical and Veterinary Sciences and the study’s lead author, said: “These findings are important as they show that SUMO modification plays a vital and previously unsuspected role in normal brain function.”
The research builds on the team’s earlier work that identified a group of proteins in the brain responsible for protecting nerve cells from damage and could be used in future for therapies for stroke and other brain diseases.
(Source: bristol.ac.uk)
Signal found to enhance survival of new brain cells
A specialized type of brain cell that tamps down stem cell activity ironically, perhaps, encourages the survival of the stem cells’ progeny, Johns Hopkins researchers report. Understanding how these new brain cells “decide” whether to live or die and how to behave is of special interest because changes in their activity are linked to neurodegenerative diseases such as Alzheimer’s, mental illness and aging.
"We’ve identified a critical mechanism for keeping newborn neurons, or new brain cells, alive," says Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine’s Institute for Cell Engineering’s Stem Cell Program. "Not only can this help us understand the underlying causes of some diseases, it may also be a step toward overcoming barriers to therapeutic cell transplantation."
Working with a group led by Guo-li Ming, M.D., Ph.D., a professor of neurology in the Institute for Cell Engineering, and other collaborators, Song’s research team first reported last year that brain cells known as parvalbumin-expressing interneurons instruct nearby stem cells not to divide by releasing a chemical signal called GABA.
In their new study, as reported Nov. 10 online in Nature Neuroscience, Song and Ming wanted to find out how GABA from surrounding neurons affects the newborn neurons that stem cells produce. Many of these newborn neurons naturally die soon after their “birth,” Song says; if they do survive, the new cells migrate to a permanent home in the brain and forge connections called synapses with other cells.
To learn whether GABA is a factor in the newborn neurons’ survival and behavior, the research team tagged newborn neurons from mouse brains with a fluorescent protein, then watched their response to GABA. “We didn’t expect these immature neurons to form synapses, so we were surprised to see that they had built synapses from surrounding interneurons and that GABA was getting to them that way,” Song says. In the earlier study, the team had found that GABA was getting to the synapse-less stem cells by a less direct route, drifting across the spaces between cells.
To confirm the finding, the team engineered the interneurons to be either stimulated or suppressed by light. When stimulated, the cells would indeed activate nearby newborn neurons, the researchers found. They next tried the light-stimulation trick in live mice, and found that when the specialized interneurons were stimulated and gave off more GABA, the mice’s newborn neurons survived in greater numbers than otherwise. This was in contrast to the response of the stem cells, which go dormant when they detect GABA.
"This appears to be a very efficient system for tuning the brain’s response to its environment," says Song. "When you have a high level of brain activity, you need more newborn neurons, and when you don’t have high activity, you don’t need newborn neurons, but you need to prepare yourself by keeping the stem cells active. It’s all regulated by the same signal."
Song notes that parvalbumin-expressing interneurons have been found by others to behave abnormally in neurodegenerative diseases such as Alzheimer’s and mental illnesses such as schizophrenia. “Now we want to see what the role of these interneurons is in the newborn neurons’ next steps: migrating to the right place and integrating into the existing circuitry,” he says. “That may be the key to their role in disease.” The team is also interested in investigating whether the GABA mechanism can be used to help keep transplanted cells alive without affecting other brain processes as a side effect.
Schizophrenia linked to abnormal brain waves
Neuroscientists discover neurological hyperactivity that produces disordered thinking
Schizophrenia patients usually suffer from a breakdown of organized thought, often accompanied by delusions or hallucinations. For the first time, MIT neuroscientists have observed the neural activity that appears to produce this disordered thinking.
The researchers found that mice lacking the brain protein calcineurin have hyperactive brain-wave oscillations in the hippocampus while resting, and are unable to mentally replay a route they have just run, as normal mice do.
Mutations in the gene for calcineurin have previously been found in some schizophrenia patients. Ten years ago, MIT researchers led by Susumu Tonegawa, the Picower Professor of Biology and Neuroscience, created mice lacking the gene for calcineurin in the forebrain; these mice displayed several behavioral symptoms of schizophrenia, including impaired short-term memory, attention deficits, and abnormal social behavior.
In the new study, which appears in the Oct. 16 issue of the journal Neuron, Tonegawa and colleagues at the RIKEN-MIT Center for Neural Circuit Genetics at MIT’s Picower Institute for Learning and Memory recorded the electrical activity of individual neurons in the hippocampus of these knockout mice as they ran along a track.
Previous studies have shown that in normal mice, “place cells” in the hippocampus, which are linked to specific locations along the track, fire in sequence when the mice take breaks from running the course. This mental replay also occurs when the mice are sleeping. These replays occur in association with very high frequency brain-wave oscillations known as ripple events.
In mice lacking calcineurin, the researchers found that brain activity was normal as the mice ran the course, but when they paused, their ripple events were much stronger and more frequent. Furthermore, the firing of the place cells was abnormally augmented and in no particular order, indicating that the mice were not replaying the route they had just run.
This pattern helps to explain some of the symptoms seen in schizophrenia, the researchers say.
“We think that in this mouse model, we may have some kind of indication that there’s a disorganized thinking process going on,” says Junghyup Suh, a research scientist at the Picower Institute and one of the paper’s lead authors. “During ripple events in normal mice we know there is a sequential replay event. This mutant mouse doesn’t seem to have that kind of replay of a previous experience.”
The paper’s other lead author is David Foster, a former MIT postdoc. Other authors are Heydar Davoudi and Matthew Wilson, the Sherman Fairchild Professor of Neuroscience at MIT and a member of the Picower Institute.
The researchers speculate that in normal mice, the role of calcineurin is to suppress the connections between neurons, known as synapses, in the hippocampus. In mice without calcineurin, a phenomenon known as long-term potentiation (LTP) becomes more prevalent, making synapses stronger. Also, the opposite effect, known as long-term depression (LTD), is suppressed.
“It looks like this abnormally high LTP has an impact on activity of these cells specifically during resting periods, or post exploration periods. That’s a very interesting specificity,” Tonegawa says. “We don’t know why it’s so specific.”
The researchers believe the abnormal hyperactivity they found in the hippocampus may represent a disruption of the brain’s “default mode network” — a communication network that connects the hippocampus, prefrontal cortex (where most thought and planning occurs), and other parts of the cortex.
This network is more active when a person (or mouse) is resting between goal-oriented tasks. When the brain is focusing on a specific goal or activity, the default mode network gets turned down. However, this network is hyperactive in schizophrenic patients before and during tasks that require the brain to focus, and patients do not perform well in these tasks.
Further studies of these mice could help reveal more about the role of the default mode network in schizophrenia, Tonegawa says.
Building the best brain: U-M researchers show how brain cell connections get cemented early in life
Research on synapse stabilization could aid understanding of autism, schizophrenia, intellectual disability
When we’re born, our brains aren’t very organized. Every brain cell talks to lots of other nearby cells, sending and receiving signals across connections called synapses.
But as we grow and learn, things get a bit more stable. The brain pathways that will serve us our whole lives start to organize, and less-active, inefficient synapses shut down.
But why and how does this happen? And what happens when it doesn’t go normally? New research from the University of Michigan Medical School may help explain.
In a new paper in Nature Neuroscience, a team of U-M neuroscientists reports important findings about how brain cells called neurons keep their most active connections with other cells, while letting other synapses lapse.
Specifically, they show that SIRP alpha, a protein found on the surface of various cells throughout the body, appears to play a key role in the process of cementing the most active synaptic connections between brain cells. The research, done in mouse brains, was funded by the National Institutes of Health and several foundations.
The findings boost understanding of basic brain development – and may aid research on conditions like autism, schizophrenia, epilepsy and intellectual disability, all of which have some basis in abnormal synapse function.
“For the brain to be really functional, we need to keep the most active and most efficient connections,” says senior author Hisashi Umemori, M.D., Ph.D., a research assistant professor at U-M’s Molecular and Behavioral Neuroscience Institute and assistant professor of biological chemistry in the Medical School. “So, during development it’s crucial to establish efficient connections, and to eliminate inactive ones. We have identified a key molecular mechanism that the brain uses to stabilize and maturate the most active connections.”
Umemori says the new findings on SIRP alpha grew directly out of previous work on competition between neurons, which enables the most active ones to become part of pathways and circuits. (Read more on this research)
The team suspected that there must be some sort of signal between the two cells on either side of each synapse — something that causes the most active synapses to stabilize. So they set out to find out what it was.
SIRP-rise findings
The group had previously shown that SIRP-alpha was involved in some way in a neuron’s ability to form a presynaptic nerve terminal – an extension of the cell that reaches out toward a neighboring cell, and can send the chemical signals that brain cells use to talk to one another.
SIRP-alpha is also already known to serve an important function in the rest of the body – essentially, helping normal cells tell the immune system not to attack them. It may also help cancer cells evade detection by the immune system’s watchdogs.
In the new study, the team studied SIRP alpha function in the brain – and started to understand its role in synapse stabilization. They focused on the hippocampus, a region of the brain very important to learning and memory.
Through a range of experiments, they showed that when a brain cell receives signals from a neighboring cell across a synapse, it actually releases SIRP-alpha into the space between the cells. It does this through the action of molecules inside the cell – called CaMK and MMP – that act like molecular scissors, cutting a SIRP-alpha protein in half so that it can float freely away from the cell.
The part of the SIRP-alpha protein that floats into the synapse “gap” latches on to a receptor on the other side, called a CD47 receptor. This binding, in turn, appears to tell the cell that the signal it sent earlier was indeed received – and that the synapse is a good one. So, the cell brings more chemical signaling molecules down that way, and releases them into the synapse.
As more and more nerve messages travel between the “sending” and “receiving” cells on either side of that synapse, more SIRP-alpha gets cleaved, released into the synapse, and bound to CD47.
The researchers believe this repeated process is what helps the cells determine which synapses to keep – and which to let wither.
Umemori says the team next wants to look at what happens when SIRP-alpha doesn’t get cleaved as it should – and at what’s happening in cells when a synapse gets eliminated.
“This step of shedding SIRP-alpha must be critical to developing a functional neural network,” he says. “And if it’s not done well, disease or disorders may result. Perhaps we can use this knowledge to treat diseases caused by defects in synapse formation.”
He notes that the gene for the CD47 receptor is found in the same general area of our DNA as several genes that are suspected to be involved in schizophrenia.
How schizophrenia affects the brain
UI study documents the illness’s effect on brain tissue
It’s hard to fully understand a mental disease like schizophrenia without peering into the human brain. Now, a study by University of Iowa psychiatry professor Nancy Andreasen uses brain scans to document how schizophrenia impacts brain tissue as well as the effects of anti-psychotic drugs on those who have relapses.
Andreasen’s study, published in the American Journal of Psychiatry, documented brain changes seen in MRI scans from more than 200 patients beginning with their first episode and continuing with scans at regular intervals for up to 15 years. The study is considered the largest longitudinal, brain-scan data set ever compiled, Andreasen says.
Schizophrenia affects roughly 3.5 million people, or about one percent of the U.S. population, according to the National Institutes of Health. Globally, some 24 million are affected, according to the World Health Organization.
The scans showed that people at their first episode had less brain tissue than healthy individuals. The findings suggest that those who have schizophrenia are being affected by something before they show outward signs of the disease.
“There are several studies, mine included, that show people with schizophrenia have smaller-than-average cranial size,” explains Andreasen, whose appointment is in the Carver College of Medicine. “Since cranial development is completed within the first few years of life, there may be some aspect of earliest development—perhaps things such as pregnancy complications or exposure to viruses—that on average, affected people with schizophrenia.”
Andreasen’s team learned from the brain scans that those affected with schizophrenia suffered the most brain tissue loss in the two years after the first episode, but then the damage curiously plateaued—to the group’s surprise. The finding may help doctors identify the most effective time periods to prevent tissue loss and other negative effects of the illness, Andreasen says.
The researchers also analyzed the effect of medication on the brain tissue. Although results were not the same for every patient, the group found that in general, the higher the anti-psychotic medication doses, the greater the loss of brain tissue.
“This was a very upsetting finding,” Andreasen says. “We spent a couple of years analyzing the data more or less hoping we had made a mistake. But in the end, it was a solid finding that wasn’t going to go away, so we decided to go ahead and publish it. The impact is painful because psychiatrists, patients, and family members don’t know how to interpret this finding. ‘Should we stop using antipsychotic medication? Should we be using less?’”
The group also examined how relapses could affect brain tissue, including whether long periods of psychosis could be toxic to the brain. The results suggest that longer relapses were associated with brain tissue loss.
The insight could change how physicians use anti-psychotic drugs to treat schizophrenia, with the view that those with the disorder can lead productive lives with the right balance of care.
“We used to have hundreds of thousands of people chronically hospitalized. Now, most are living in the community, and this is thanks to the medications we have,” Andreasen notes. “But antipsychotic treatment has a negative impact on the brain, so … we must get the word out that they should be used with great care, because even though they have fewer side effects than some of the other medications we use, they are certainly not trouble free and can have lifelong consequences for the health and happiness of the people and families we serve.”
(Source: now.uiowa.edu)
Cell transplants may be a novel treatment for schizophrenia
Rodent research suggests feasibility of restoring neuron function
Research from the School of Medicine at The University of Texas Health Science Center at San Antonio suggests the exciting possibility of using cell transplants to treat schizophrenia.
Cells called “interneurons” inhibit activity within brain regions, but this braking or governing function is impaired in schizophrenia. Consequently, a group of nerve cells called the dopamine system go into overdrive. Different branches of the dopamine system are involved in cognition, movement and emotions.
“Since these cells are not functioning properly, our idea is to replace them,” said study senior author Daniel Lodge, Ph.D., assistant professor of pharmacology in the School of Medicine.
Transplant restored normal function
Dr. Lodge and lead author Stephanie Perez, graduate student in his laboratory, biopsied tissue from rat fetuses, isolated cells from the tissue and injected the cells into a brain center called the hippocampus. This center regulates the dopamine system and plays a role in learning, memory and executive functions such as decision making. Rats treated with the transplanted cells have restored hippocampal and dopamine function.
Stem cells are able to become different types of cells, and in this case interneurons were selected. “We put in a lot of cells and not all survived, but a significant portion did and restored hippocampal and dopamine function back to normal,” Dr. Lodge said.
‘You can essentially fix the problem’
Unlike traditional approaches to treating schizophrenia, such as medications and deep-brain stimulation, transplantation of interneurons potentially can produce a permanent solution. “You can essentially fix the problem,” Dr. Lodge said. “Ultimately, if this is translated to humans, we want to reprogram a patient’s own cells and use them.”
After meeting with other students, Perez brought the research idea to Dr. Lodge. “The students have journal club, and somebody had done a similar experiment to restore motor deficits and had good results,” Perez said. “We thought, why can’t we use it for schizophrenia and have good results, and so far we have.”
The study is in Molecular Psychiatry.
(Source: uthscsa.edu)
Genetic breakthrough another step to understanding schizophrenia
A consortium of scientists from 20 countries, including researchers from The University of Western Australia, has made a major breakthrough in understanding the genetic basis of the debilitating disorder, schizophrenia.
More than 175 scientists from 99 institutions across Europe, the United States of America and Australia contributed to a genome-wide association analysis which identified 13 new risk loci for schizophrenia.
In an article published in the journal, Nature Genetics, the study authors write that the results provide deeper insight into the genetic architecture of schizophrenia than ever before achieved, and provide a pathway to further research.
"For the first time, there is a clear path to increased knowledge of the etiology of schizophrenia through the application of standard, off-the-shelf genomic technologies for elucidating the effects of common variation," the authors wrote.
Schizophrenia is a complex mental disorder which affects about one per cent of people over their lifetime, leading to prolonged or recurrent episodes that impair severely social functioning and quality of life.
In terms of the ‘global burden of disease and disability’ index, developed by the World Health Organization, it ranks among the top 10 disorders, along with cancer, heart disease, diabetes and other non-communicable diseases.
Winthrop Professor Assen Jablensky, director of UWA’s Centre for Clinical Research in Neuropsychiatry (CCRN) at Graylands Hospital, and Professor Luba Kalaydjieva, of the UWA-affiliated Western Australian Institute for Medical Research (WAIMR), led the UWA research team which took part in the study.
Professor Jablensky said that while a strong genetic component in the causation of schizophrenia had been well established, the role of specific genes and the mechanisms of their regulation remained largely unknown.
"Until recently, results of genetic linkage and association studies could explain only a small fraction of the estimated heritability of the disorder and of its ‘genetic architecture’," Professor Jablensky said.
However recent technological advances, enabling efficient coverage of the entire human genome with millions of single nucleotide polymorphisms (SNPs) as genetic markers, had given rise to a new generation of genome-wide association studies (GWAS), which trace the DNA differences between people affected with the disease and healthy control individuals.
"Since the effects of individual SNPs are quite tiny, their reliable measurement requires very large samples of adequately diagnosed patients and controls," Professor Jablensky said.
"This recent study reports on a major breakthrough in the understanding of the genetic basis of schizophrenia, achieved through meta-analysis of GWAS datasets contributed by a large international Psychiatric Genomics Consortium (PGC) - which includes the UWA research team."
A WA case-control sample consisting of 893 schizophrenia patients and healthy controls was part of a collection of 21,246 schizophrenia cases and 38,072 controls from 19 research centres and consortia across Europe, Australia and the USA.
The study found that a total of 8300 SNPs contribute to the risk for schizophrenia and account for at least 32 per cent of the variance in liability.
"A particularly important result of this study is that many of these SNPs are located on a molecular pathway involved in neuronal calcium signalling, which suggests a novel pathogenetic link in the causation of schizophrenia and possibly other psychotic disorders," Professor Jablensky said.
He said ongoing and future studies by the UWA research team would aim to further refine the genetic analyses of the WA schizophrenia study (which at present includes 1259 persons), and to test neurobiological hypotheses about the treatment responses of genetically defined subsets of patients.
(Source: news.uwa.edu.au)