Category: Schizophrenia

Antipsychotic medications are increasingly prescribed in the US, but they can cause serious side effects including rapid weight gain, especially in children. In the first study of its kind, researchers at Zucker Hillside Hospital and the Feinstein Institute for Medical Research identified a gene that increases weight gain in those treated with commonly-used antipsychotic drugs.

These findings were published in the May issue of Archives of General Psychiatry.

Second-generation antipsychotics (SGAs) were used as the treatment in this study. SGAs are commonly used to treat many psychotic and nonpsychotic disorders. However, it is important to note that these SGAs are associated with substantial weight gain, including the development of obesity and other cardiovascular risk factors. The weight gain side effect of SGAs is significant because it often results in a reduced life expectancy of up to 30 years in those who suffer from chronic and severe mental illnesses. The weight gain also prompts some to stop taking the medication, adversely impacting their quality of life.

In this genome-wide association study (GWAS), researchers first evaluated a group of pediatric patients in the US being treated for the first time with antipsychotics. They then replicated the result in three independent groups of patients who were in psychiatric hospitals in the United States and Germany or participating in European antipsychotic drug trials. The gene that was identified to increase weight gain, MC4R or melanocortin 4 receptor, has been previously identified as being linked to obesity and type 2 diabetes. In the new study, it was found that patients gained up to 20 pounds when on treatment.

"This study offers the prospect of being able to identify individuals who are at greatest risk for severe weight gain following antipsychotic treatment," said Anil Malhotra, MD, investigator at the Zucker Hillside Hospital Department of Psychiatry Research and Feinstein Institute for Medical Research. "We hope that those who are at risk could receive more intensive or alternative treatment that would reduce the potential for weight gain and we are currently conducting studies to identify such treatment."

Additional Details About the Study

Researchers conducted the first GWAS of SGA-induced weight gain in patients carefully monitored for medication adherence who were undergoing initial treatment with SGAs. To confirm results, they next assessed three independent replication cohorts: 1) a cohort of adult subjects undergoing their first treatment with a single SGA (clozapine), 2) a cohort of adult subjects treated with the same SGAs as in our discovery sample, and 3) a cohort of adult subjects in the first episode of schizophrenia and enrolled in a randomized clinical trial of antipsychotic drugs. The discovery cohort consisted of 139 pediatric patients undergoing first exposure to SGAs. The 3 additional cohorts consisted of 73, 40, and 92 subjects. Patients in the discovery cohort were treated with SGAs for 12 weeks. Additional cohorts were treated for 6 and 12 weeks.

This GWAS yielded 20 single-nucleotide polymorphisms at a single locus exceeding a statistical threshold of P10-5. This locus, near the melanocortin 4 receptor (MC4R) gene, overlaps a region previously identified by large-scale GWAS of obesity in the general population. Effects were recessive, with minor allele homozygotes gaining extreme amounts of weight during the 12-week trial. These results were replicated in 3 additional cohorts, with rs489693 demonstrating consistent recessive effects; meta-analysis revealed a genome-wide significant effect. Moreover, consistent effects on related metabolic indices, including triglyceride, leptin, and insulin levels were observed.

A pioneering new study finds that a specific type of computerized cognitive training can lead to significant neural and behavioral improvements in individuals with schizophrenia. The research, published by Cell Press in the February 23 issue of the journal Neuron, reveals that 16 weeks of intensive cognitive training is also associated with improved social functioning several months later and may have far-reaching implications for improving the quality of life for patients suffering from neuropsychiatric illness.

Schizophrenia is a debilitating psychiatric illness that is associated with severe clinical symptoms, such as hallucinations and delusions, as well as substantial social and cognitive deficits. "Schizophrenia patients struggle with 'reality monitoring,' the ability to separate the inner world from the outer reality," states senior author, Dr. Sophia Vinogradov. "Although there are drugs that reduce the clinical symptoms of schizophrenia, current medications do not improve cognitive deficits. In addition, conventional psychotherapy has not proven to be successful, and there is a pressing need for new therapeutic strategies."

In the current study, scientists from the University of California, San Francisco, took a unique approach to enhancing behavior and brain activation in individuals with schizophrenia. "We predicted that in order to improve complex cognitive functions in neuropsychiatric illness, we must initially target impairments in lower-level perceptual processes, as well as higher-order working memory and social cognitive processes," explains senior study author, Dr. Srikantan Nagarajan.

The first author, Dr. Karuna Subramaniam, who conducted the study and analyzed the data, found that when compared with pretraining assessments, schizophrenia patients who received 80 hours of computerized training (over 16 weeks) exhibited improvements in their ability to perform complex reality-monitoring tasks, which were associated with increased activation of the medial prefrontal cortex (mPFC). The mPFC is a critical brain region that supports successful reality-monitoring processes. "We found that the level of mPFC activation was also linked with better social functioning six months after training," says Dr. Subramaniam. "In contrast, patients in a control group who played computer games for 80 hours did not show any improvements, demonstrating that the behavioral and neural improvements were specific to the computerized training patient group."

"Our study is the first to demonstrate that neuroscience-informed cognitive training can lead to more 'normal' brain-behavior associations in patients with schizophrenia, which in turn predict better social functioning months later," concludes Dr. Vinogradov. "These findings raise the exciting likelihood that the neural impairments in schizophrenia — and undoubtedly other neuropsychiatric illnesses — are not immutably fixed, but instead may be amenable to well-designed interventions that target restoration of neural system functioning."

A team of neuroscientists led by a Wayne State University School of Medicine professor has discovered stark developmental differences in brain network function in children of parents with schizophrenia when compared to those with no family history of mental illness.

The study, led by Vaibhav Diwadkar, Ph.D., assistant professor of psychiatry and behavioral neurosciences and co-director of the Division of Brain Research and Imaging Neuroscience, was published in the March 2012 issue of the American Medical Association journal Archives of General Psychiatry and is titled, "Disordered Corticolimbic Interactions During Affective Processing in Children and Adolescents at Risk for Schizophrenia Revealed by Functional Magnetic Resonance Imaging and Dynamic Causal Modeling."

The results provide significant insight into plausible origins of schizophrenia in terms of dysfunctional brain networks in adolescence, demonstrate sophisticated analyses of functional magnetic resonance imaging (fMRI) data and clarify the understanding of developmental mechanisms in normal versus vulnerable brains. The resulting information can provide unique information to psychiatrists.

The study took place over three years, using MRI equipment at Harper University Hospital in Detroit. Using fMRI the researchers studied brain function in young individuals (8 to 20 years of age) as they observed pictures of human faces depicting positive, negative and neutral emotional expressions. Participants were recruited from the metropolitan Detroit area. Because children of patients are at highly increased risk for psychiatric illnesses such as schizophrenia, the team was interested in studying brain network function associated with emotional processing and the relevance of impaired network function as a potential predictor for schizophrenia.

To investigate brain networks, the researchers applied advanced analyses techniques to the fMRI data to investigate how brain regions dynamically communicate with each other. The study demonstrated that children at risk for the illness are characterized by reduced network communication and disordered network responses to emotional faces. This suggests that brain developmental processes are going awry in children whose parents have schizophrenia, suggesting this is a subgroup of interest to watch in future longitudinal studies.

"Brain network dysfunction associated with emotional processing is a potential predictor for the onset of emotional problems that may occur later in life and that are in turn associated with illnesses like schizophrenia," Diwadkar said. "If you clearly demonstrate there is something amiss in how the brain functions in children, there is something you can do about it. And that's what we're interested in."

The results don't show whether schizophrenia will eventually develop in the subjects. "It doesn't mean that they have it, or that they will have it," he said.

"The kids we studied were perfectly normal if you looked at them," he said. "By using functional brain imaging we are trying to get underneath behavior."

"We are able to do this because we can investigate dynamic changes in brain network function by assessing changes in the fMRI signal. This allowed us to capture dramatic differences in how regions in the brain network are interacting with each other," he said.

According to the National Alliance on Mental Illness, schizophrenia affects men and women with equal frequency, but generally manifests in men in their late teens or early 20s, and in women in their late 20s or early 30s.

Diwadkar worked with Wayne State medical student Sunali Wadehra, M.A., and colleagues at Harvard Medical School and the University of Pittsburgh School of Medicine. Global collaborator Simon Eickhoff, Dr.Med., of Research Center Jülich and the Institute of Clinical Neuroscience and Medical Psychology at Heinrich-Heine University Düsseldorf, in Germany, also provided significant insight.

This study was supported by the National Institute of Mental Health of the National Institutes of Health along with the Children's Research Center of Michigan; the National Alliance for Research on Schizophrenia and Depression (Diwadkar); the Joe Young Sr.; the Office of the Vice President, Wayne State University; and the German Research Foundation.

People with schizophrenia who completed 80 hours of intensive, computerized cognitive training exercises were better able to perform complex tasks that required them to distinguish their internal thoughts from reality.

As described in the journal Neuron, a small clinical study conducted at the San Francisco VA Medical Center (SFVAMC) and the University of California, San Francisco (UCSF), tested the digital exercises as a new therapy for schizophrenia.

"We predicted that in order to improve complex cognitive functions in neuropsychiatric illness, we must target impairments in lower-level perceptual processes, as well as higher-order working-memory and social cognitive processes," said Srikantan Nagarajan, PhD, a professor of radiology and biomedical imaging at UCSF and a senior author of the study.

When compared with their assessments before the training, schizophrenia patients who received 80 hours of computerized training over the course of 16 weeks became better at monitoring reality. This improvement coincided with increased activation in a key part of the brain: the medial prefrontal cortex.

"The medial prefrontal cortex is a critical higher-order brain region that supports successful reality-monitoring processes," said Karuna Subramaniam, the study's first author, who worked directly with the patients in the study and analyzed their data.

HOW THE STUDY WORKED Schizophrenia strikes about 1 percent of all Americans and about 51 million people worldwide. It is one of the most intractable and difficult to treat psychiatric illnesses, with prognosis becoming progressively poorer the longer a patient has the disease, according to the study's senior author, Sophia Vinogradov, MD, professor and interim associate chief of staff for mental Health at SFVAMC and interim vice chair of psychiatry at UCSF.

One of the core impairments of the disease is losing a grip on what is real, she said. "Reality-monitoring is the ability to separate the inner world from outer reality," she explained. "It is a complex cognitive function that is impaired in schizophrenia."

In the study, the brains of 31 patients with schizophrenia and 15 healthy people used for comparison were scanned using functional magnetic resonance imaging (fMRI) while they performed a reality-monitoring task.

Then, 16 of the 31 patients with schizophrenia were randomly assigned to complete 80 hours of computerized training composed of auditory, visual and social cognitive exercises that included programs designed by the Posit Science Corporation. The other 15 patients with schizophrenia were assigned to play computer games for the same amount of time.

After 80 hours, all of the subjects repeated the original reality-monitoring task in the MRI scanner, to monitor brain activity associated with their ability to discern words they made up in their head (internally-generated information) from words the experimenter showed them (externally-presented information).

The reality-monitoring test consisted of a study phase and a retrieval phase. During the study phase, subjects read sentences with noun-verb-noun structures outside the scanner. These were simple sentences like: "The chicken crossed the road." During this study phase, the final word of each sentence was either presented by the scientists or it was left blank for subjects to make up and fill in themselves (e.g., "The rabbit ate the ___" to which the subject might write down, "carrot").

Then, 45 minutes later, the subjects performed the retrieval phase in the MRI scanner where their brain activity was monitored while they were shown pairs of nouns from the sentence list. They had to identify whether the second word in the noun pair was a word that they had previously generated themselves during the study phase ("rabbit-carrot") or was one that the experimenter had presented to them ("chicken-road").

Compared to their pre-training assessments, people who had received the computerized cognitive training were better able to distinguish between the words they had made up themselves and those that had been presented to them. Furthermore, analyses of the MRI data revealed they also had increased activity in the part of the brain (the medial prefrontal cortex) that governs these decisions.

"Interestingly, greater activation within the medial prefrontal cortex was also linked with better social functioning six months after training," Subramaniam said. "In contrast, patients in the computer games control condition did not show any improvements, demonstrating that the behavioral and neural changes were specific to the computerized training patient group."

What this suggests, said Vinogradov, is that "the neural impairments in schizophrenia are not immutably fixed but may be amenable to well-designed interventions that target restoration of neural system functioning."

The study "sets the groundwork for what could be a new treatment approach in psychiatric illness — a new tool we could use in addition to medication, psychotherapeutic approaches or cognitive behavioral approaches," she said.

The article, "Computerized Cognitive Training Restores Neural Activity within the Reality Monitoring Network in Schizophrenia" by Karuna Subramaniam, Tracy L. Luks, Melissa Fisher, Gregory V. Simpson, Srikantan Nagarajan, and Sophia Vinogradov appears in the Feb. 23 issue of Neuron.

This work was funded by the National Institute of Mental Health. Gregory Simpson, an author of the study, is a senior scientist at Brain Plasticity Institute, Inc. Sophia Vinogradov, also a study author, is a consultant to Brain Plasticity Institute, Inc., which has a financial interest in computerized cognitive training programs.

Scientists at Case Western Reserve University School of Medicine found a way to rapidly produce pure populations of cells that grow into the protective myelin coating on nerves in mice. Their process opens a door to research and potential treatments for multiple sclerosis, cerebral palsy and other demyelinating diseases afflicting millions of people worldwide.

The findings were published in the online issue of Nature Methods on Sept. 25.

"The mouse cells that we utilized, which are pluripotent epiblast stem cells, can make any cell type in body," Paul Tesar, an assistant professor of genetics at Case Western Reserve and senior author of the study, explained. "So our goal was to devise precise methods to specifically turn them into pure populations of myelinating cells, called oligodendrocyte progenitor cells, or OPCs."

Their success holds promise for basic research and beyond.

"The ability of these methods to produce functional cells that restore myelin in diseased mice provides a solid framework for the ability to produce analogous human cells for use in the clinic," said Robert H. Miller, vice dean for research at the school of medicine and an author of the paper.

Tesar worked with CWRU School of Medicine researchers Fadi J. Najm, Shreya Nayak, and Peter C. Scacheri, from the department of genetics; Anita Zaremba, Andrew V. Caprariello and Miller, from the department of neurosciences; and with Eric. C. Freundt, now at the University of Tampa.

Myelin protects nerve axons and provides insulation needed for signals to pass along nerves intact. Loss of the coating results in damage to nerves and diminished signal-carrying capacity, which can be expressed outwardly in symptoms such as loss of coordination and cognitive function.

Scientists believe that manipulating a patient's own OPCs or transplanting OPCs could be a way to restore myelin.

And, they have long known that pluripotent stem cells have the potential to differentiate into OPCs. But, efforts to push stem cells in that direction have resulted in a mix of cell types, unsuitable for studying the developmental process that produces myelin, or to be used in therapies.

Tesar and colleagues are now able to direct mouse stem cells into oligodendrocyte progenitor cells in just 10 days. The team's success relied upon guiding the cells through specific stages that match those that occur during normal embryonic development.

First, stem cells in a petri dish are treated with molecules to direct them to become the most primitive cells in the nervous system. These cells then organize into structures called neural rosettes reminiscent of the developing brain and spinal cord.

To produce OPCs, the neural rosettes are then treated with a defined set of signaling proteins previously known to be important for generation of OPCs in the developing spinal cord.

After this 10 day protocol, the researchers were able to maintain the OPCs in the lab for more than a month by growing them on a specific protein surface called laminin and adding growth factors associated with OPC development.

The OPCs were nearly homogenous and could be multiplied to obtain more than a trillion cells.

The OPCs were treated with thyroid hormone, which is key to regulating the transition of the OPCs to oligodendrocytes. The result was the OPCs stopped proliferating and turned into oligodendrocytes within four days.

Testing on nerves lacking myelin, both on the lab bench and in diseased mouse models, showed the OPCs derived from the process flourished into oligodendrocytes and restored normal myelin within days, demonstrating their potential use in therapeutic transplants.

Because they are able to produce considerable numbers of OPCs — a capability that up until now has been lacking — the researchers have created a platform for discovering modulators of oligodendrocyte differentiation and myelination. This may be useful for developing drugs to turn a patient's own cells into myelinating cells to counter disease.

The National Institutes of Health, CWRU School of Medicine, the New York Stem Cell Foundation, the Myelin Repair Foundation, the National Center for Regenerative Medicine, and the Case Comprehensive Cancer Center funded the research.

Journal Reference:

1. Fadi J Najm, Anita Zaremba, Andrew V Caprariello, Shreya Nayak, Eric C Freundt, Peter C Scacheri, Robert H Miller, Paul J Tesar. Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells. Nature Methods, 2011; DOI: 10.1038/nmeth.1712

Columbia University Medical Center researchers have shown that new, or "de novo," protein-altering mutations — genetic errors that are present in patients but not in their parents — play a role in more than 50 percent of "sporadic" — i.e., not hereditary — cases of schizophrenia.

The findings will be published online on August 7, 2011, in Nature Genetics.

A group led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhD, examined the genomes of patients with schizophrenia and their families, as well as healthy control groups. All were from the genetically isolated, European-descent Afrikaner population of South Africa.

These findings build on earlier studies by Karayiorgou, professor of psychiatry at Columbia University Medical Center. More than 15 years ago, Karayiorgou and her colleagues described a rare de novo mutation that accounts for 1-2 percent of sporadic cases of schizophrenia. With advances in technology, three years ago the Columbia team was able to search the entire genome for similar lesions that insert or remove small chunks of DNA. The mutations found accounted for about 10 percent of sporadic cases.

Encouraged by their progress, they wondered whether other, previously undetectable, de novo mutations accounted for an even greater percentage of sporadic cases. Using state-of-the-art "deep sequencing," they examined the nucleotide bases of almost all the genes in the human genome. This time they found 40 mutations, all from different genes and most of them protein-altering. The results point the way to finding more, perhaps even hundreds, of mutations that contribute to the genetics of schizophrenia — a necessary step toward understanding how the disease develops.

"Identification of these damaging de novo mutations has fundamentally transformed our understanding of the genetic basis of schizophrenia," says Bin Xu, PhD, assistant professor of clinical neurobiology at Columbia University Medical Center and first author of the study.

"The fact that the mutations are all from different genes," says Karayiorgou, "is particularly fascinating. It suggests that many more mutations than we suspected may contribute to schizophrenia. This is probably because of the complexity of the neural circuits that are affected by the disease; many genes are needed for their development and function." Karayiorgou and her team will now search for recurring mutations, which may provide definitive evidence that any specific mutation contributes to schizophrenia.

The potentially large number of mutations makes a gene-therapy approach to treating schizophrenia unlikely. Researchers suspect, however, that all of the mutations affect the same neural circuitry mechanisms. "Using innovative neuroscience methods," says co-author Dr. Joseph Gogos, MD, PhD, and associate professor of physiology and neuroscience at Columbia University Medical Center, "we hope to identify those neural circuit dysfunctions, so we can target them for drug development."

The study's results also help to explain two puzzles: the persistence of schizophrenia, despite the fact that those with the disease do not tend to pass down their mutations through children; and the high global incidence of the disease, despite large environmental variations.

The study was supported by NIMH, the Lieber Center for Schizophrenia Research at Columbia University, and NARSAD.

Journal Reference:

1. Bin Xu, J Louw Roos, Phillip Dexheimer, Braden Boone, Brooks Plummer, Shawn Levy, Joseph A Gogos, Maria Karayiorgou. Exome sequencing supports a de novo mutational paradigm for schizophrenia. Nature Genetics, 2011; DOI: 10.1038/ng.902

NewsPsychology (July 13, 2011) — Research to be presented at the upcoming annual meeting of the Society for the Study of Ingestive Behavior (SSIB), the foremost society for research into all aspects of eating and drinking behavior, may explain why some antipsychotic drugs can promote overeating, weight gain, and insulin resistance.

Olanzapine, an atypical antipsychotic drug approved by the FDA for the treatment of schizophrenia and bipolar disorder, has been associated with body weight gain and impaired glucose homeostasis in humans and in experimental animals. As part of a Dutch research consortium, studies led by Simon Evers (University of Groningen, the Netherlands) sought to reveal underlying mechanisms for olanzapine’s metabolic effects by studying healthy adult male volunteers. The research was motivated by observations of what co-author Anton Scheurink described as “a mysterious interaction between schizophrenia and diabetes.”

Their results confirmed previous findings that olanzapine induces weight gain by increasing caloric intake, but also revealed that olanzapine reduces body temperature, which contributes to decreased energy expenditure. Indeed, reduced body temperature after olanzapine treatment may generate many of the known side effects of this antipsychotic drug. The authors’ new findings also demonstrate that olanzapine alters peripheral glucose metabolism, which may contribute to impaired insulin sensitivity.

According to lead author Simon Evers, “Our research group believes that reduced body temperature is the foremost direct and consistent effect of olanzapine in humans and in experimental animals. Reduced body temperature might explain several of olanzapine’s metabolic side effects, including increased food intake, reduced energy expenditure, sedation, high blood sugar, body weight gain, and insulin resistance.”

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The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Society for the Study of Ingestive Behavior.

De novo mutations — genetic errors that are present in patients but not in their parents — are more frequent in schizophrenic patients than in normal individuals, according to an international group of scientists led by Dr. Guy A. Rouleau of the University of Montreal and CHU Sainte-Justine Hospital. The discovery, published in Nature Genetics, may enable researchers to define how the disease results from these mutations and eventually develop new treatments for it.

"The occurrence of de novo mutations, as observed in this study, may in part explain the high worldwide incidence of schizophrenia," says Dr. Rouleau, who is also Director of the CHU Sainte-Justine Research Center and researcher at the University of Montreal Hospital Research Centre. "Because the mutations are located in many different genes, we can now start to establish genetic networks that would define how these gene mutations predispose to schizophrenia," adds Simon Girard, the student who performed the key experiments that led to this discovery. "Most of the genes identified in this study have not been previously linked to schizophrenia, thereby providing new potential therapeutic targets."

Schizophrenia is a major mental disorder characterized by a wide spectrum of symptoms, including delusions, hallucinations, disturbances in thinking, and deterioration of social behaviours. According to the World Health Organization, as many as 24 million individuals worldwide suffer from schizophrenia and over half of them are not receiving appropriate care to relieve their symptoms.

Dr. Rouleau's team used modern DNA sequencing technologies to identify genetic changes in patients with schizophrenia whose parents showed no signs of the disease. To identify genetic mutations associated with schizophrenia, Dr. Rouleau and his team analysed approximately 20,000 genes from each participant in the study. The research team was especially interested in "de novo" mutations, meaning those that are present in patients but absent in their parents.

"Our results not only open the door to a better understanding of schizophrenia," adds Dr. Rouleau. "They also give us valuable information about the molecular mechanisms involved in human brain development and function."

The identification of de novo mutations in schizophrenia supports the hypothesis proposed by Dr. Rouleau in 2006, that this type of mutation plays a role in several diseases affecting brain development such as autism, schizophrenia and mental retardation.

"Increased exonic de novo mutation rate in probands affected with schizophrenia" was published online on July 10, 2011 in Nature Genetics. The authors are Simon L. Girard, Julie Gauthier, Anne Noreau, Lan Xiong, Sirui Zhou, Loubna Jouan, Alexandre Dionne-Laporte, Dan Spiegelman, Edouard Henrion, Ousmane Diallo, Pascale Thibodeau, Isabelle Bachand, Jessie Y.J. Bao, Amy Hin Yan Tong, Chi-Ho Lin, Bruno Millet, Nematollah Jaafari, Ridha Joober, Patrick A. Dion, Si Lok, Marie-Odile Krebs, and Guy A. Rouleau.

This research was funded in large part by Genome Canada and Génome Québec, with contributions by the Canadian Institutes of Health Research (CIHR) and the Brain and Behavior Research Foundation (formerly NARSAD, the National Alliance for Research on Schizophrenia and Depression) and the University of Montreal. The University of Montreal is officially known as Université de Montréal.

Journal Reference:

1. Simon L Girard, Julie Gauthier, Anne Noreau, Lan Xiong, Sirui Zhou, Loubna Jouan, Alexandre Dionne-Laporte, Dan Spiegelman, Edouard Henrion, Ousmane Diallo, Pascale Thibodeau, Isabelle Bachand, Jessie Y J Bao, Amy Hin Yan Tong, Chi-Ho Lin, Bruno Millet, Nematollah Jaafari, Ridha Joober, Patrick A Dion, Si Lok, Marie-Odile Krebs, Guy A Rouleau. Increased exonic de novo mutation rate in individuals with schizophrenia. Nature Genetics, 2011; DOI: 10.1038/ng.886

Understanding the actions of other people can be difficult for those with schizophrenia. Vanderbilt University researchers have discovered that impairments in a brain area involved in perception of social stimuli may be partly responsible for this difficulty.

"Misunderstanding social situations and interactions are core deficits in schizophrenia," said Sohee Park, Gertrude Conaway Professor of Psychology and one of the co-authors on this study. "Our findings may help explain the origins of some of the delusions involving perception and thoughts experienced by those with schizophrenia."

In findings published in the journal PLoS ONE, the researchers found that a particular brain area, the posterior superior temporal sulcus or STS, appears to be implicated in this deficit.

"Using brain imaging together with perceptual testing, we found that a brain area in a neural network involved in perception of social stimuli responds abnormally in individuals with schizophrenia," said Randolph Blake, Centennial Professor of Psychology and co-author. "We found this brain area fails to distinguish genuine biological motion from highly distorted versions of that motion."

The study's lead author, Jejoong Kim, completed the experiments as part of his dissertation under the supervision of Park and Blake in Vanderbilt's Department of Psychology. Kim is now conducting research in the Department of Brain and Cognitive Sciences at Seoul National University in Korea, where Blake is currently a visiting professor.

"We have found… that people with schizophrenia tend to 'see' living things in randomness and this subjective experience is correlated with an increased activity in the (posterior) STS," the authors wrote. "In the case of biological motion perception, these self-generated, false impressions of meaning can have negative social consequences, in that schizophrenia patients may misconstrue the actions or intentions of other people."

In their experiments, the researchers compared the performance of people with schizophrenia to that of healthy controls on two visual tasks. One task involved deciding whether or not an animated series of lights depicted the movements of an actor's body. The second task entailed judging subtle differences in the actions depicted by two similar animations viewed side by side. On both tasks, people with schizophrenia performed less well than the healthy controls.

fMRI used to ID brain area

Next, the researchers measured brain activity using functional magnetic resonance imaging (fMRI) while the subjects — healthy controls and schizophrenia patients — performed a version of the side-by-side task. Once again, the individuals with schizophrenia performed worse on the task. The researchers were then able to correlate those performance deficits with the brain activity in each person.

The fMRI results showed strong activation of the posterior portion of the STS in the healthy controls when they were shown biological motion. In the individuals with schizophrenia, STS activity remained relatively constant and high regardless of what was presented to them.

Analysis of the brain activity of the schizophrenia patients also showed high STS activity on trials where they reported seeing biological motion, regardless of whether the stimulus itself was biological or not.

For reasons yet to be discovered, area STS in schizophrenia patients fails to differentiate normal human activity from non-human motion, leading Kim and colleagues to surmise that this abnormal brain activation contributes to the patients' difficulties reading social cues portrayed by the actions of others.

The National Research Foundation of Korea in the Korean Ministry of Education, Science and Technology funded the research.

Journal Reference:

1. Jejoong Kim, Sohee Park, Randolph Blake. Perception of Biological Motion in Schizophrenia and Healthy Individuals: A Behavioral and fMRI Study. PLoS ONE, 2011; 6 (5): e19971 DOI: 10.1371/journal.pone.0019971

 There is a significant need for objective tests that could improve clinical prediction of future psychosis.

In this new study, the researchers followed a group of people clinically at high risk for developing psychosis. They found that the individuals who went on to develop schizophrenia had smaller MMN than the subgroup who did not. This finding suggests that MMN might be useful in predicting the later development of schizophrenia.

One strategy has been to determine whether physiologic measures that are abnormal in people diagnosed with schizophrenia might also be useful in estimating the risk for developing this illness. This is the strategy taken by German and Swiss researchers in the current issue of Biological Psychiatry.

They used electroencephalography (EEG), which measures the brain's electrical activity or "brain waves," to study the brain's response to commonly and rarely presented tones that differed in length.

When these rare "deviant" tones are presented to healthy people, the brain automatically generates a particular electrical wave called mismatch negativity, or MMN. People diagnosed with schizophrenia have reduced MMN.

In this new study, the researchers followed a group of people clinically at high risk for developing psychosis. They found that the individuals who went on to develop schizophrenia had smaller MMN than the subgroup who did not. This finding suggests that MMN might be useful in predicting the later development of schizophrenia.

"With this type of study, the devil is always in the details. How sensitive is MMN as a risk predictor? How reliable is it? How many people are mistakenly classified? How long of a follow-up period is necessary to make this test useful? Are there subgroups of individuals for whom this test is or is not reliable?" mused Dr. John Krystal, Editor of Biological Psychiatry. "If we hope to use this type of measure to guide research and even clinical interventions, then it has to be an extremely robust measure with respect to the issues that I just mentioned, among others. Yet, this is exactly the type of initial step that we need to move toward clinically meaningful biological tests."

First author Dr. Mitja Bodatsch agreed, adding that "integration of both biological and clinical measures into multidimensional models might be the crucial next step forward to improve risk staging in psychiatry."

Journal Reference:

1. Mitja Bodatsch, Stephan Ruhrmann, Michael Wagner, Ralf Müller, Frauke Schultze-Lutter, Ingo Frommann, Jürgen Brinkmeyer, Wolfgang Gaebel, Wolfgang Meier, Joachim Klosterkötter. Prediction of Psychosis by Mismatch Negativity. Schizophrenia Research, 2010; 117 (2-3): 244 DOI: 10.1016/j.schres.2010.02.372