Posts tagged schizophrenia
Articles and news from the latest research reports.
Eye Movements and the Search for Biomarkers for Schizophrenia
There is a long history of research on impaired eye movements associated with schizophrenia. Using a series of simple viewing tests, researchers of a new paper in Biological Psychiatry explored the ability of these eye movement tests to distinguish people with and without the diagnosis of schizophrenia.
Using their complete dataset, they were able to develop a model that could discriminate all schizophrenia cases from healthy control subjects with an impressive 98.3% accuracy.
Drs. Philip Benson and David St. Clair, lead authors on the paper, agreed that their findings were remarkable: “It has been known for over a hundred years that individuals with psychotic illnesses have a variety of eye movement abnormalities, but until our study, using a novel battery of tests, no one thought the abnormalities were sensitive enough to be used as potential clinical diagnostic biomarkers.”
Their battery of tests included smooth pursuit, free-viewing, and gaze fixation tasks. In smooth pursuit, people with schizophrenia have well-documented deficits in the ability to track slow-moving objects smoothly with their eyes. Their eye movements tend to fall behind the moving object and then catch-up with the moving object using a rapid eye movement, called a saccade.. A picture is displayed in the free-viewing test, and where most individuals follow a typical pattern with their gaze as they scan the picture, those with schizophrenia follow an abnormal pattern. In a fixation task, the instruction is to keep a steady gaze on a single unmoving target, which tends to be difficult for individuals with schizophrenia.
As expected, the researchers found that the performance of individuals with schizophrenia was abnormal compared to the healthy volunteer group on each of the eye tests. At right is an example of the differences, with the eye tracking of a schizophrenia case in red and a healthy control in blue.
The researchers then used several methods to model the data. The accuracy of each of the created algorithms was then tested by using eye test data from another group of cases and controls. Combining all the data, one of the models achieved 98.3% accuracy.
"It is encouraging to see the high sensitivity of this model for the diagnosis of schizophrenia. It will be interesting to see the extent to which this approach enables clinical investigators to distinguish people with schizophrenia from individuals with other psychiatric disorders," commented Dr. John Krystal, Editor of Biological Psychiatry.
Benson and St Clair have already started that work, stating, “We now have exciting unpublished data showing that patterns of eye movement abnormalities are specific to different psychiatric subgroups, another key requirement for diagnostic biomarkers. The next thing we want to know is when the abnormalities are first detectable and can they be used as disease markers for early intervention studies in major mental illness?”
"We are also keen to explore how best our findings can be developed for use in routine clinical practice," they added. Typical neuropsychological assessments are time-consuming, expensive, and require highly trained individuals to administer. In comparison, these eye tests are simple, cheap, and take only minutes to conduct. This means that a predictive model with such precision could potentially be incorporated in clinics and hospitals to aid physicians by augmenting traditional symptom-based diagnostic criteria.
(Source: alphagalileo.org)
Are Schizophrenia and Autism Close Relations?
TAU researcher discovers that family history of schizophrenia is a risk factor for autism
Autism Spectrum Disorders (ASD), a category that includes autism, Asperger Syndrome, and Pervasive Developmental Disorder, are characterized by difficulty with social interaction and communication, or repetitive behaviors. The U.S. Centers for Disease Control and Management says that one in 88 children in the US is somewhere on the Autism spectrum — an alarming ten-fold increase in the last four decades.
New research by Dr. Mark Weiser of Tel Aviv University’s Sackler Faculty of Medicine and the Sheba Medical Center has revealed that ASD appears share a root cause with other mental illnesses, including schizophrenia and bipolar disorder. At first glance, schizophrenia and autism may look like completely different illnesses, he says. But closer inspection reveals many common traits, including social and cognitive dysfunction and a decreased ability to lead normal lives and function in the real world.
Studying extensive databases in Israel and Sweden, the researchers discovered that the two illnesses had a genetic link, representing a heightened risk within families. They found that people who have a schizophrenic sibling are 12 times more likely to have autism than those with no schizophrenia in the family. The presence of bipolar disorder in a sibling showed a similar pattern of association, but to a lesser degree.
A scientific leap forward, this study sheds new light on the genetics of these disorders. The results will help scientists better understand the genetics of mental illness, says Dr. Weiser, and may prove to be a fruitful direction for future research. The findings have been published in the Archives of General Psychiatry.
All in the family
Researchers used three data sets, one in Israel and two in Sweden, to determine the familial connection between schizophrenia and autism. The Israeli database alone, used under the auspices of the ethics committees of both the Sheba Medical Center and the Israeli Defense Forces, included anonymous information about more than a million soldiers, including patients with schizophrenia and ASD.
"We found the same results in all three data sets," he says, noting that the ability to replicate the findings across these extensive databases is what makes this study so significant.Understanding this genetic connection could be a missing link, Dr. Weiser says, and provides a fresh direction for study. The researchers are now taking this research in a clinical direction. For now, though, the findings shouldn’t influence the way that doctors treat patients with either illness, he adds.
(Source: aftau.org)
A Gene Implicated In Schizophrenia Risk Is Also Associated With Risk for Cannabis Dependence
A paper by Shizhong Han and colleagues in the current issue of Biological Psychiatry implicates a new gene in the risk for cannabis dependence. This gene, NRG1, codes for the ErbB4 receptor, a protein implicated in synaptic development and function.
The researchers set out to investigate susceptibility genes for cannabis dependence, as research has already shown that it has a strong genetic component.
To do this, they employed a multi-stage design using genetic data from African American and European American families. In the first stage, a linkage analysis, the strongest signal was identified in African Americans on chromosome 8p21. Then using a genome-wide association study dataset, they identified one genetic variant at NRG1 that showed consistent evidence for association in both African Americans and European Americans. Finally, they replicated the association of that same variant in an independent sample of African-Americans.
All together, the findings suggest that NRG1 may be a susceptibility gene for cannabis dependence.
An interesting feature of this paper is that these findings may also suggest a link between the genetics of schizophrenia and the genetics of cannabis dependence. NRG1 emerged into public awareness after a series of genetic studies implicated it in the heritable risk for schizophrenia. Subsequent studies in post-mortem brain tissue also suggested that the regulation of NRG1 was altered in the brains of individuals diagnosed with schizophrenia.
Thus, the current findings may help to explain the already established link between cannabis use and the risk for developing schizophrenia. A number of epidemiologic studies have attributed the association of cannabis use and schizophrenia to the effects of cannabis on the brain rather than a common genetic link between these two conditions.
"The current data provide a potentially important insight into the heritable risk for schizophrenia and raise the possibility that there are some common genetic contributions to these two disorders," commented Dr. John Krystal, Editor of Biological Psychiatry.
However, further research will be necessary to further confirm the role that NRG1 plays in cannabis dependence and the potential link between cannabis use and psychosis.
(Source: alphagalileo.org)
Rare genetic disorder points to molecules that may play role in schizophrenia
Scientists studying a rare genetic disorder have identified a molecular pathway that may play a role in schizophrenia, according to new research in the Oct. 10 issue of The Journal of Neuroscience. The findings may one day guide researchers to new treatment options for people with schizophrenia — a devastating disease that affects approximately 1 percent of the world’s population.
Schizophrenia is characterized by a multitude of symptoms, including hallucinations, social withdrawal, and learning and memory deficits, which usually appear during late adolescence or early adulthood. Efforts to identify disease causes have been complicated by the fact that no single genetic mutation is strongly associated with the disease. By studying a rare genetic disorder that increases the risk of schizophrenia, Laurie Earls, PhD, and colleagues in the laboratory of Stanislav Zakharenko, MD, PhD, at St. Jude Children’s Research Hospital identified molecular changes that affect memory and are also present in people with schizophrenia.
Approximately 30 percent of people with a genetic disorder known as 22q11 deletion syndrome develop schizophrenia, making it one of the strongest risk factors for the disease. In previous studies of mice with the 22q11 deletion, Zakharenko’s group identified changes in nerve cells leading to deficits in the hippocampus — the brain’s learning and memory center — that appear with age. In the current study, the group confirmed similar molecular changes occur in people with schizophrenia. They also zeroed in on the gene contributing to the nerve cell changes.
"This study makes some very important discoveries about the precise mechanisms underlying the learning and memory deficits seen in the genetic mouse model — problems that are a central part of the human disease," said Carrie Bearden, PhD, an expert on 22q11 deletion syndrome at the University of California, Los Angeles, who was not involved in the study. "Pinpointing the specific gene involved is the first step toward developing targeted therapies that could reverse the cognitive deficits associated with schizophrenia, both in the context of this genetic mutation and the broader population," she added.
In previous studies, Zakharenko’s group found that abnormal nerve cell communication and cognitive dysfunction was associated with elevated levels of a protein that regulates calcium in certain nerve cells known as Serca2. These abnormalities are only detectable with age in mice with the 22q11 deletion.
In the current study, the researchers identified the gene Dgcr8 as the source of the changes.It produces molecules called microRNAs that normally keep Serca2 in check. Without them, the protein becomes elevated.By adding these molecules back into the hippocampus of animals with the 22q11 deletion, the researchers were able to reduce elevated Serca2 levels and reduce the cellular deficits associated with this genetic defect.
To assess whether the findings from these genetic mouse studies might translate to schizophrenia, the authors analyzed post-mortem brain tissue from people with schizophrenia. The researchers discovered that Serca2 was elevated even in patients with schizophrenia who did not have the 22q11 deletion.
"These data suggest a link between the nerve cell changes in patients with the 22q11 deletion syndrome and those that occur in patients with schizophrenia," Zakharenko said. "Serca2 regulation represents a novel therapeutic target for schizophrenia."
(Source: sott.net)
New de novo Genetic Mutations in Schizophrenia Identified
Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease. The study, the largest and most comprehensive of its kind, was published today in the online edition of the journal Nature Genetics.
Although schizophrenia typically onsets during adolescence and early adulthood, many of the mutations were found to affect genes with higher expression during early-to-mid fetal development. Together, the findings show that both the function of the mutated gene and when the gene is expressed are critically important in determining the risk for schizophrenia.
The findings inform epidemiologic studies showing that environmental factors, such as malnutrition or infections during pregnancy, can contribute to the development of schizophrenia. “Our findings provide a mechanism that could explain how prenatal environmental insults during the first and second trimester of pregnancy increase one’s risk for schizophrenia,” said study leader Maria Karayiorgou, MD, professor of psychiatry at CUMC, and acting chief, division of Psychiatric and Medical Genetics, New York State Psychiatric Institute. “Patients with these mutations were much more likely to have had behavioral abnormalities, such as phobias and anxiety in childhood, as well as worse disease outcome.”
Study explores how brain disruption may foster schizophrenia
Yale University researchers have discovered an innovative way to study how large brain systems are organized, an advance that has already provided insights into diseases such as schizophrenia.
The Yale team used a combination of neuroimaging, computational neurobiology, and pharmacological techniques to reveal functioning at both the cellular level and across larger brain regions.
In a paper in Proceedings of the National Academy of Sciences the week of Sept. 24, Yale scientists use this approach to show that a disruption of a particular signaling mechanisms within larger neural systems may be contribute to schizophrenia symptoms.
The eyes may be windows into the soul, but following their movement also could allow doctors to make quick, accurate diagnoses for disorders like autism, schizophrenia, or attention deficit hyperactivity disorder, various research projects suggest.
Eye tracking, which records where subjects focus when watching visual displays, could diagnose brain disorders more accurately than subjective questionnaires or medical examinations do, researchers say. Exams are expensive and time-consuming, and subjective tests have been known to wrongly identify healthy people or misdiagnose disorders.
To make sense of all that people see, the brain filters huge amounts of visual information, fills in gaps and focuses on certain objects. That complex task uses many mental circuits, so differences in what people choose to look at ― differences so subtle that only a computer can spot them ― could provide unprecedented insight into common neurological problems.
New algorithm can analyze information from medical images to identify diseased areas of the brain and connections with other regions.
Disorders such as schizophrenia can originate in certain regions of the brain and then spread out to affect connected areas. Identifying these regions of the brain, and how they affect the other areas they communicate with, would allow drug companies to develop better treatments and could ultimately help doctors make a diagnosis. But interpreting the vast amounts of data produced by brain scans to identify these connecting regions has so far proved impossible.
Now, researchers in the Computer Science and Artificial Intelligence Laboratory at MIT have developed an algorithm that can analyze information from medical images to identify diseased areas of the brain and their connections with other regions.
The MIT researchers will present the work next month at the International Conference on Medical Image Computing and Computer Assisted Intervention in Nice, France.
With a little training, signs of schizophrenia are averted
August 22, 2012
Animals that literally have holes in their brains can go on to behave as normal adults if they’ve had the benefit of a little cognitive training in adolescence. That’s according to new work in the August 23 Neuron, a Cell Press publication, featuring an animal model of schizophrenia, where rats with particular neonatal brain injuries develop schizophrenia-like symptoms.
"The brain can be loaded with all sorts of problems," said André Fenton of New York University. "What this work shows is that experience can overcome those disabilities."
Fenton’s team made the discovery completely by accident. His team was interested in what Fenton considers a core problem in schizophrenia: the inability to sift through confusing or conflicting information and focus on what’s relevant.
"As you walk through the world, you might be focused on a phone conversation, but there are also kids in the park and cars and other distractions," he explained. "These information streams are all competing for our brain to process them. That’s a really challenging situation for someone with schizophrenia."
Fenton and his colleagues developed a laboratory test of cognitive control needed for that kind of focus. In the test, rats had to learn to avoid a foot shock while they were presented with conflicting information. Normal rats can manage that task quickly. Rats with brain lesions can also manage this task, but only up until they become young adults—the equivalent of an 18- or 20-year-old person—when signs of schizophrenia typically set in.
While that was good to see, Fenton says, it wasn’t really all that surprising. But then some unexpected circumstances in the lab led them to test animals with adolescent experience in the cognitive control test again, once they had grown into adults.
These rats should have shown cognitive control deficits, similar to those that had not received prior cognitive training, or so the researchers thought. Instead, they were just fine. Their schizophrenic symptoms had somehow been averted.
Fenton believes their early training for focus forged some critical neural connections, allowing the animals to compensate for the injury still present in their brains in adulthood. Not only were the animals’ behaviors normalized with training, but the patterns of activity in their brains were also.
The finding is consistent with the notion that mental disorders are the consequence of problems in brain development that might have gotten started years before. They raise the optimistic hope that the right kinds of experiences at the right time could change the future by enabling people to better manage their diseases and better function in society. Adolescence, when the brain undergoes significant change and maturation, might be a prime time for such training.
"You may have a damaged brain, but the consequences of that damage might be overcome without changing the damage itself," Fenton says. "You could target schizophrenia, but other disorders aren’t very different," take autism or depression, for example.
And really, in this world of infinite distraction, couldn’t we all use a little more cognitive control?
Source: medicalxpress.com
Mount Sinai Researchers Identify New Drug Target for Schizophrenia
August 13, 2012
Researchers at Mount Sinai School of Medicine may have discovered why certain drugs to treat schizophrenia are ineffective in some patients. Published online in Nature Neuroscience, the research will pave the way for a new class of drugs to help treat this devastating mental illness, which impacts one percent of the world’s population, 30 percent of whom do not respond to currently available treatments.
A team of researchers at Mount Sinai School of Medicine set out to discover what epigenetic factors, or external factors that influence gene expression, are involved in this treatment-resistance to atypical antipsychotic drugs, the standard of care for schizophrenia. They discovered that, over time, an enzyme in the brains of schizophrenic patients analyzed at autopsy begins to compensate for the prolonged chemical changes caused by antipsychotics, resulting in reduced efficacy of the drugs.
"These results are groundbreaking because they show that drug resistance may be caused by the very medications prescribed to treat schizophrenia, when administered chronically," said Javier Gonzalez-Maeso, PhD, Assistant Professor of Psychiatry and Neurology at Mount Sinai School of Medicine and lead investigator on the study.
They found that an enzyme called HDAC2 was highly expressed in the brain of mice chronically treated with antipsychotic drugs, resulting in lower expression of the receptor called mGlu2, and a recurrence of psychotic symptoms. A similar finding was observed in the postmortem brains of schizophrenic patients. The research team administered a chemical called suberoylanilide hydroxamic acid (SAHA), which inhibits the entire family of HDACs. They found that this treatment prevented the detrimental effect of the antipsychotic called clozapine on mGlu2 expression, and also improved the therapeutic effects of atypical antipsychotics in mouse models.
Previous research conducted by the team showed that chronic treatment with the antipsychotic clozapine causes repression of mGlu2 expression in the frontal cortex of mice, a brain area key to cognition and perception. The researchers hypothesized that this effect of clozapine on mGlu2 may play a crucial role in restraining the therapeutic effects of antipsychotic drugs.
"We had previously found that chronic antipsychotic drug administration causes biochemical changes in the brain that may limit the therapeutic effects of these drugs,"said Dr. Gonzalez-Maeso. "We wanted to identify the molecular mechanism responsible for this biochemical change, and explore it as a new target for new drugs that enhance the therapeutic efficacy of antipsychotic drugs."
Mitsumasa Kurita, PhD, a postdoctoral fellow at Mount Sinai and the lead author of the study, said, “We found that atypical antipsychotic drugs trigger an increase of HDAC2 in frontal cortex of individuals with schizophrenia, which then reduces the presence of mGlu2, and thereby limits the efficacy of these drugs,” said
Dr. Gonzalez-Maeso’s team is now developing compounds that specifically inhibit HDAC2 as adjunctive treatments to antipsychotics. The study was funded by the National Institutes of Health.
Source: The Mount Sinai Hospital