A New Way to Predict, and Treat, Psychotic Illness

Psychotic illness is a relatively rare but often severe form of mental illness, affecting around one in 100 people at some point in their lives. It most commonly begins in adolescence and early adulthood, but onset can occur later during adulthood and even in the advanced years.
People with a psychotic illness may have a genetic predisposition, but not via a single gene. Multiple genes appear to be involved, as well as environmental factors such as stress, illicit drug use and social factors.
Methods of diagnosing psychotic illness haven’t changed in the past 15 to 20 years. Psychiatrists still rely on observing symptoms, then make informed guesses about the best course of treatment.
But emerging tools may offer a more sophisticated way of diagnosing psychotic illness, predicting the future course of the disease and providing early and specific treatment.

Symptoms and severity

People with psychotic illness can appear paranoid and may perceive their environment, and even friends and family, as hostile.
Signs of psychotic illness include abnormal sensory perception (such as visual hallucinations), changes in mood, disturbed thinking, reduced motivation, and a decline in function at work or school or University. Sleep problems can also occur.
Experience of psychotic illness varies from person to person but tends to follow one of four general courses. The first is the person has only one episode during their lifetime, with a full recovery afterwards.
The second course of illness includes multiple episodes of psychosis during the person’s lifetime, but they fully recover and go back to normal life between those episodes. These people usually need regular treatment.
In the third form, the multiple episodes of psychosis lead to progressive decline in day-to-day function. They don’t fully recover between single episodes, and worsen over time.
Finally, the most severe form of the illness is where the first episode of the disease leads to a severe decline in daily function, and the constant presence of severe signs and symptoms that require intensive treatment.

Problems diagnosing the disease

When the first signs and symptoms occur, psychiatrists cannot determine with enough certainty what type of illness course will likely take place, and what type of treatment should be provided and which treatments are unnecessary. This means treatment and interventions are reactive rather than preventive.
Unlike physical illnesses, we can’t rely on blood tests, brain scans or other biological tests. As a consequence of this lack of diagnostic accuracy, our field purely relies purely on observation.
But there is growing evidence that individual illness progression is dependent on a wide range of factors, including social, demographic, clinical, psychological and biological factors.

Towards a more sophisticated approach

My research team has developed a potential alternative to diagnosing and treating patients with severe mental illness, and psychosis in particular.
Our model integrates a range of diagnostic factors including clinical symptoms, cognitive abilities (memory, concentration, attention), MRI scans of the brain’s structure (to determine abnormal brain structure and function & loss of brain volume in circumscribed brain areas), and biomarkers (inflammatory biomarkers, neurotrophic biomarkers) in the patient’s blood, each of which play a specific role in the development and course of the illness.
When we use these factors individually, the prediction is usually poor. But when they’re taken together and are integrated in a meaningful way using appropriate prediction modelling as apply these in our research unit, then the likelihood with which the course of illness can be predicted increases significantly.
It may also help determine the patient’s treatment needs early and more specifically. Patients who are likely to progress to severe illness may be offered treatment earlier, for instance.
And those who are unlikely to develop severe illness may avoid unnecessary treatment – and the severe side effects.

Next steps in research

Our proposed approach would require a change in clinical practice. Clinicians would need to obtain a range of clinical, psychological and biological data from their patients in order to reach meaningful clinical conclusions and predictions rather than continue the pure trial-and-error approach. Collaboration between clinicians and specialist centres would be necessary to determine the disease trajectory.
But we’re not quite there, yet. We are currently re-analysing original data of previous studies in psychotic disorders and of ongoing research to show that our model works with currently available patient data. We are also testing our model on other groups of diagnoses, such as depression.
Should this approach prove to be valid, feasible and practicable after further rigorous testing and refinement, it could radically change clinical practice. We’re hoping it will one day help patients change the course of their illness and their lives for the better.
Bernhard Baune receives funding from National Health and Medical Research Council.
src .livescience.com/

Contact Sports Athletes More Likely to Carry MRSA

College athletes who play football, soccer and other contact sports are more likely to harbor the superbug methicillin-resistant Staphylococcus aureus (MRSA) than athletes who play non-contact sports, a new study suggests.
In the study, contact sports athletes were more than twice as likely to carry MRSA in their noses and throats, and they tended to carry the microbe for longer periods of time, compared with athletes in non-contact sports such as baseball and golf.
Over the course of the two-year study of college athletes, between 8 and 31 percent of contact sports athletes carried MRSA at any given time, compared with 0 to 23 percent of athletes in non-contact sports, and 5 to 10 percent of the general population.
None of the college athletes had symptoms of MRSA infection, but carrying the bacteria can increase the risk of infection, the researchers said.
MRSA is a type of staph bacteria that is resistant to the antibiotics typically used to treat the infection. It can cause skin infections, and if it enters the body, it can cause serious infections of the blood, heart, bone, joints and central nervous system, the researchers said.
Contact sports athletes are at higher risk for carrying MRSA, or becoming infected with the bacteria, because they have skin-to-skin contact with other players, and can have cuts that allow the bacteria to enter the body, the researchers said.
Although previous studies focused on MRSA outbreaks among college athletes, the new study is one of the first to look at athletes who carry the bacteria without symptoms, the researchers said.
"This study shows that even outside of a full-scale outbreak, when athletes are healthy and there are no infections, there are still a substantial number of them who are colonized with these potentially harmful bacteria," study researcher Natalia Jimenez-Truque, a research instructor at Vanderbilt University Medical Center in Nashville, Tennessee, said in a statement.
Athletes can reduce their risk of carrying or spreading MRSA infection by practicing good hygiene, including washing hands frequently, and not sharing towels, soap, razors and other personal items, Jimenez-Truque said. Athletes should also cover open wounds and shower after practices and games.
The study followed 377 athletes from Vanderbilt University playing 14 different sports, including football, soccer, basketball and lacrosse, baseball, cross-country and golf. Each month, the researchers took nose and throat swabs from the athletes to test for MRSA bacteria.
The study was presented today (Oct. 9) at IDWeek 2014, the annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society.
src livescience.com/

New Two-Step Strategy for Weakening Cancer

 

A cancer cell under attack by lymphocytes. Credit: thinkstockphotos.com/Rice University

Researchers from Rice University and the University of Texas MD Anderson Cancer Center reveal a new two-step strategy for weakening cancer.
Research by Rice University scientists who are fighting a cyberwar against cancer finds that the immune system may be a clinician’s most powerful ally.
“Recent research has found that cancer is already adept at using cyberwarfare against the immune system, and we studied the interplay between cancer and the immune system to see how we might turn the tables on cancer,” said Rice University’s Eshel Ben-Jacob, co-author of a new study this week in the Early Edition of the Proceedings of the National Academy of Sciences.
Ben-Jacob and colleagues at Rice’s Center for Theoretical Biological Physics (CTBP) and the University of Texas MD Anderson Cancer Center, developed a computer program that modeled a specific channel of cell-to-cell communication involving exosomes. Exosomes are tiny packets of proteins, messenger RNA and other information-coding segments that both cancer and immune cells make and use to send information to other cells.
“Basically, exosomes are small cassettes of information that are packed and sealed inside small nanoscale vesicles,” Ben-Jacob said. “These nanocarriers are addressed with special markers so they can be delivered to specific types of cells, and they contain a good deal of specific information in the form of signaling proteins, snippets of RNA, microRNAs and other data. Once taken by the target cells, these nanocarriers can order cells to change what they are doing and in some cases even change their identity.”
Ben-Jacob said recent research showed that dendritic cells use exosomal communications to carry out their specialized role as moderators of and mediators between the innate and adaptive immune systems. The innate and adaptive immune systems use different strategies to protect the body from disease. The innate system guards against all threats at all times and is the first to act even against unrecognized invaders. In contrast, the adaptive immune system acts more efficiently, and in a specific way, against recognized, established threats. Dendritic cells, which are part of both the innate and adaptive systems, share information and help “coach” the adaptive system’s hunter-killer cells about which cells to target and how best to destroy them.
“We were inspired to do this research by two papers — one that showed how the dendritic cells use the exosome to fight cancer and another that showed how cancer cells co-opt the exosomal system both to prevent the bone marrow from making dendritic cells and disable dendritic cells’ coaching abilities,” Ben-Jacob said. “This is cyberwarfare, pure and simple. Cancer uses the immune systems’ own communications network to attack not the soldiers but the generals that are coordinating the body’s defense.”
To examine the role of exosome-mediated cell-to-cell communication in the battle between cancer in the immune system, Ben-Jacob and postdoctoral fellow Mingyang Lu, the study’s first author, worked with CTBP colleagues to create a computer model that captured the special aspects of the exosomal exchange between cancer cells, dendritic cells and the other cells in the immune system.
“You should imagine there is a tug-of-war between the cancer and the immune system,” said study co-author and CTBP co-director José Onuchic, Rice’s Harry C. and Olga K. Wiess Professor of Physics and Astronomy. “Sometimes one side wins and sometimes the other. The question is whether we can understand this battle enough to use radiotherapy or chemotherapy in such a way as to change the balance of the tug-of-war in favor of the immune system.”
Based on their findings, Ben-Jacob and Onuchic say the answer is likely yes. In particular, the CTBP model found that the presence of exosomes creates a situation where three possible cancer states can exist, and one of the states — an intermediate state in which cancer is neither strong nor weak but the immune system is on high alert — could be the key for a new therapeutic approach and with reduced side effects.
“When exosomes are not included, there are only two possible states — one where cancer is strong and the immune system is weak and the other where cancer is weak and the immune system is strong,” Ben-Jacob said.
Although the state where cancer is weakened is preferable, there is a growing body of clinical evidence that suggests it is very difficult to force cancer directly from the strong to the weak position, in part because radiation and chemotherapeutic treatments also weaken the immune system as they weaken cancer.
“It is fairly common that a cancer recedes following treatment only to return stronger than ever in just a few months or weeks,” said study co-author Sam Hanash, professor of clinical cancer prevention and director of the Red and Charlene McCombs Institute for the Early Detection and Treatment of Cancer at MD Anderson. “The new model captures this dynamic and suggests alternative scenarios whereby the immune system does its job fighting the cancer.”
Ben-Jacob said the team showed that it was possible to force cancer from the strong to the moderate state by alternating cycles of radiation or chemotherapy with immune-boosting treatments.
“Our model shows that just a few of these treatment-boosting cycles can alter the cancer-immune balance to help the immune system bring the cancer to the moderate state,” Ben-Jacob said. “Once in the intermediate state, cancer can be brought further down to the weak state by a few short pulses of immune boosting.
“It is much more effective to use a two-step process and drive cancer from the strong to the intermediate state and then from the intermediate to the weak state,” he said. “Without the exosome — the cancer-immune cyberwar nanocarriers — and the third state, this two-step approach wouldn’t be possible.”
Ben-Jacob is a senior investigator at CTBP, adjunct professor of biochemistry and cell biology at Rice and the Maguy-Glass Chair in Physics of Complex Systems and professor of physics and astronomy at Tel Aviv University.
In addition to Ben-Jacob, Onuchic and Lu, study co-authors include Rice graduate student Bin Huang and Sam Hanash, director of the Red and Charline McCombs Institute for the Early Detection and Treatment of Cancer at the University of Texas MD Anderson Cancer Center. The research was supported by the Cancer Prevention and Research Institute of Texas, the National Science Foundation and the Tauber Family Funds.
Publication: Mingyang Lu, et al., “Modeling putative therapeutic implications of exosome exchange between tumor and immune cells,” PNAS, 2014; doi: 10.1073/pnas.1416745111
Source: Jade Boyd, Rice University News
Image: thinkstockphotos.com/Rice University,src http://scitechdaily.com/

Yale Researchers Detail How Blood Vessels Stay Fit

In a newly published study, researchers from Yale University detail a key molecular fitness signal that prevents vessels from becoming narrow and developing dangerous plaques.
Blood vessels need constant maintenance if they are to remain healthy. Yale researchers describe a key molecular fitness signal that prevents vessels from becoming narrow and developing dangerous plaques.
The research appears in the September 23 issue of the journal Science Signaling. Researchers found that blood vessels in mice lacking signal fibroblast growth factor receptor 1 became narrower and accumulated deleterious smooth muscle cells, seen in red in the accompanying photos. “We found FGFR1 to be crucial to maintaining normalcy,” said Yale’s Michael Simons, senior author of the study. The knowledge should help design better therapy to maintain vascular health and to prevent vessel narrowing that occurs in many life-threatening illnesses.
Abstract:
Abnormal vascular homeostasis can lead to increased proliferation of smooth muscle cells and deposition of extracellular matrix, resulting in neointima formation, which contributes to vascular lumen narrowing, a pathology that underlies diseases including transplant vasculopathy, the recurrence of stenosis, and atherosclerosis. Growth of neointima is in part due to endothelial-to-mesenchymal transition (EndMT), a transforming growth factor–β (TGFβ)–driven process, which leads to increased numbers of smooth muscle cells and fibroblasts and deposition of extracellular matrix. We reported that endothelial cell–specific knockout of fibroblast growth factor receptor 1 (FGFR1) led to activation of TGFβ signaling and development of EndMT in vitro and in vivo. Furthermore, EndMT in human diseased vasculature correlated with decreased abundance of FGFR1. These findings identify FGFR1 as the key regulator of TGFβ signaling and EndMT development.
Publication: Pei-Yu Chen, et al., “Fibroblast growth factor receptor 1 is a key inhibitor of TGFβ signaling in the endothelium,” Sci. Signal., 23 September 2014, Vol. 7, Issue 344, p. ra90; DOI: 10.1126/scisignal.2005504
Source: Bill Hathaway, Yale University News
Image: Yale University News,src http://scitechdaily.com/