First stem cell study of bipolar disorder yields promising results

March 26, 2014 by  
Filed under Featured, Research

A press release about some intriguing research:

What makes a person bipolar, prone to manic highs and deep, depressed lows? Why does bipolar disorder run so strongly in families, even though no single gene is to blame? And why is it so hard to find new treatments for a condition that affects 200 million people worldwide?

These cells, made from the skin of people with bipolar disorder, may help scientists understand the condition & develop new treatments.

These cells, made from the skin of people with bipolar disorder, may help scientists understand the condition & develop new treatments.

These cells, made from the skin of people with bipolar disorder, may help scientists understand the condition & develop new treatments.

New stem cell research published by scientists from the University of Michigan Medical School, and fueled by the Heinz C. Prechter Bipolar Research Fund, may help scientists find answers to these questions.

The team used skin from people with bipolar disorder to derive the first-ever stem cell lines specific to the condition. In a new paper inTranslational Psychiatrythey report how they transformed the stem cells into neurons, similar to those found in the brain – and compared them to cells derived from people without bipolar disorder.

The comparison revealed very specific differences in how these neurons behave and communicate with each other, and identified striking differences in how the neurons respond to lithium, the most common treatment for bipolar disorder.

It’s the first time scientists have directly measured differences in brain cell formation and function between people with bipolar disorder and those without.

The researchers are from the Medical School’s Department of Cell & Developmental Biology and Department of Psychiatry, and U-M’s Depression Center.

Stem cells as a window on bipolar disorder

The team used a type of stem cell called induced pluripotent stem cells, or iPSCs. By taking small samples of skin cells and exposing them to carefully controlled conditions, the team coaxed them to turn into stem cells that held the potential to become any type of cell. With further coaxing, the cells became neurons.

“This gives us a model that we can use to examine how cells behave as they develop into neurons. Already, we see that cells from people with bipolar disorder are different in how often they express certain genes, how they differentiate into neurons, how they communicate, and how they respond to lithium,” says Sue O’Shea, Ph.D., the experienced U-M stem cell specialist who co-led the work.

A small skin sample from a person with bipolar disorder can yield stem cells that can be coaxed to become neurons just like those in the brain.

A small skin sample from a person with bipolar disorder
can yield stem cells that can be coaxed to become
neurons just like those in the brain. 

“We’re very excited about these findings. But we’re only just beginning to understand what we can do with these cells to help answer the many unanswered questions in bipolar disorder’s origins and treatment,” says Melvin McInnis, M.D., principal investigator of the Prechter Bipolar Research Fund and its programs.

“For instance, we can now envision being able to test new drug candidates in these cells, to screen possible medications proactively instead of having to discover them fortuitously.”

The research was supported by donations from the Heinz C. Prechter Bipolar Research Fund, the Steven M. Schwartzberg Memorial Fund, and the Joshua Judson Stern Foundation. The A. Alfred Taubman Medical Research Institute at the U-M Medical School also supported the work, which was reviewed and approved by the U-M Human Pluripotent Stem Cell Research Oversight committee and Institutional Review Board.

O’Shea, a professor in the Department of Cell & Developmental Biology and director of the U-M Pluripotent Stem Cell Research Lab, and McInnis, the Upjohn Woodworth Professor of Bipolar Disorder and Depression in the Department of Psychiatry, are co-senior authors of the new paper.

McInnis, who sees firsthand the impact that bipolar disorder has on patients and the frustration they and their families feel about the lack of treatment options, says the new research could take treatment of bipolar disorder into the era of personalized medicine.

Not only could stem cell research help find new treatments, it may also lead to a way to target treatment to each patient based on their specific profile – and avoid the trial-and-error approach to treatment that leaves many patients with uncontrolled symptoms.

More about the findings:

These neurons - derived from stem cells made from the skin of people with bipolar disorder - communicated with one another differently than neurons made from the skin of people without bipolar disorder.

These neurons – derived from stem cells made from the skin of people with bipolar disorder – communicated with one another differently than neurons made from the skin of people without bipolar disorder.

The skin samples were used to derive the 42 iPSC lines. When the team measured gene expression first in the stem cells, and then re-evaluated the cells once they had become neurons, very specific differences emerged between the cells derived from bipolar disorder patients and those without the condition.

Specifically, the bipolar neurons expressed more genes for membrane receptors and ion channels than non-bipolar cells, particularly those receptors and channels involved in the sending and receiving of calcium signals between cells.

Calcium signals are already known to be crucial to neuron development and function. So, the new findings support the idea that genetic differences expressed early during brain development may have a lot to do with the development of bipolar disorder symptoms – and other mental health conditions that arise later in life, especially in the teen and young adult years.

Meanwhile, the cells’ signaling patterns changed in different ways when the researchers introduced lithium, which many bipolar patients take to regulate their moods, but which causes side effects. In general, lithium alters the way calcium signals are sent and received – and the new cell lines will make it possible to study this effect specifically in bipolar disorder-specific cells.

Like misdirected letters and packages at the post office, the neurons made from bipolar disorder patients also differed in how they were ‘addressed’ during development for delivery to certain areas of the brain. This may have an impact on brain development, too.

The researchers also found differences in microRNA expression in bipolar cells – tiny fragments of RNA that play key roles in the “reading” of genes. This supports the emerging concept that bipolar disorder arises from a combination of genetic vulnerabilities.

The researchers are already developing stem cell lines from other trial participants with bipolar disorder, though it takes months to derive each line and obtain mature neurons that can be studied. They will share their cell lines with other researchers via the Prechter Repository at U-M. They also hope to develop a way to use the cells to screen drugs rapidly, called an assay.

Haiming Chen, M.D., and Cindy DeLong, Ph.D., manager of the pluripotent stem cell core laboratory, are co-first authors of the paper.

Reference: Translational Psychiatry, early online publication, March 25, 2014.

 

Suicide of 9-Year-Old Isn’t School’s Fault

March 10, 2014 by  
Filed under Advocacy, Commentary

Jack Bouboushian reports on Courthouse News:

A Texas school district is not liable for a bullied fourth grader’s tragic suicide in the school nurse’s bathroom, the 5th Circuit ruled.

Montana Lance was just 9 years old when he hanged himself with his belt in a bathroom of the school nurse’s office in 2010.

The child had just returned to Stewarts Creek Elementary School after an eight-day stint at an alternative school where he went for pulling a penknife on Stewarts Creek classmates who had threatened him.

Read more on Courthouse News.

How is that we have zero tolerance cases that result in children being suspended for pointing their fingers like guns, but when it comes to students being harassed or bullied, schools that seemingly do not do enough to stop and prevent bullying are not liable?

If children can be held responsible for their conduct, when will we hold the schools fully responsible and accountable for their inaction or lack of safeguards?

North Shore-LIJ Doctors Testing New Tourette Syndrome Drug

March 10, 2014 by  
Filed under Research

The North Shore-LIJ Health System’s Movement Disorders Center will be one of nine sites in the United States taking part in a clinical trial of a new drug for Tourette syndrome, the health system announced today.

The drug, AZD5213, targets the histamine H3 receptor. Histamine is commonly associated with allergies and the immune system, but it also plays a role in regulating dopamine and the neurotransmitter is intimately tied to the symptoms of Tourette.

The trial was sparked by geneticists identifying a rare mutation in a gene for histidine decarboxylase (Hdc) in a family with Tourette syndrome – a father and his eight sons.

The mutation, which blocks histamine production, has only been found in that family, but researchers have created transgenic mice with the same mutation and those animals develop Tourette and compulsive-like behaviors. The animal studies showed that the mutations disrupted dopamine modulation and that histamine infusion reduced the dopamine levels.

“That scientists have replicated it in an animal model validates the hypothesis that the pathophysiology may be similar in human patients,” said Cathy Budman, MD, director of the Movement Disorders Program in Psychiatry, investigator at the Feinstein Institute for Medical Research and expert on Tourette syndrome who will oversee the study site for North Shore-LIJ.

The study will test safety, tolerability, pharmacokinetics and efficacy in adolescent patients, between 12 and 17 years old. In addition to safety, the Yale Global Tic Severity Scale will be used to see whether tics were reduced while on the study drug.

“We are hoping that this new investigational drug will prove to be effective for patients,” said Dr. Budman.

According to the 2007 National Survey of Children’s Health (NSCH), an estimated three in 1,000 children will develop Tourette syndrome although up to 1/200 may show milder tic symptoms. It is three times as likely in boys as in girls. Most patients experience their worst symptoms during adolescence, but symptoms may persist throughout life. Many patients also suffer from other conditions, including attention deficit-hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD). Anxiety, depression and anger control problems can also complicate the disease.

The brain chemistry changes that have been identified in Tourette open the door to the development of effective treatments. AZD5213 may be able to counteract these changes, with the potential to provide symptomatic relief with less of the negative side effects associated with existing treatments, said Dr. Budman.

For more information on the clinical trial, call study coordinator Arif Hafeez at 516-562-3224.

About North Shore-LIJ 

One of the nation’s largest health systems, North Shore-LIJ delivers world-class clinical care throughout the New York metropolitan area, pioneering research at The Feinstein Institute for Medical Research and a visionary approach to medical education highlighted by the Hofstra North Shore-LIJ School of Medicine. North Shore-LIJ cares for people at every stage of life at 16 hospitals and nearly 400 outpatient physician practices throughout the region. North Shore-LIJ’s owned hospitals and long-term care facilities house more than 6,000 beds, employ more than 10,000 nurses and have affiliations with more than 9,400 physicians. With a workforce of more than 47,000, North Shore-LIJ is the largest private employer in New York State. For more information, go tohttp://www.northshorelij.com.

About The Feinstein Institute for Medical Research

Headquartered in Manhasset, NY, The Feinstein Institute for Medical Research is home to international scientific leaders in many areas including Parkinson’s disease, Alzheimer’s disease, psychiatric disorders, rheumatoid arthritis, lupus, sepsis, human genetics, pulmonary hypertension, leukemia, neuroimmunology, and medicinal chemistry. The Feinstein Institute, part of the North Shore-LIJ Health System, ranks in the top 6th percentile of all National Institutes of Health grants awarded to research centers. For more information, visit http://www.FeinsteinInstitute.org.

SOURCE: PRWEB, March 5, 2014

Long Island: Study on OCD seeks research participants

February 13, 2014 by  
Filed under Research

As I’ve done in the past, I am posting a research recruitment notice for the benefit of those who might be interested in participating. The study has nothing to do with me or my websites and is presented only as a courtesy. As in other cases, a copy of the university’s Institutional Review Board approval was submitted with the request to post this announcement.

A new clinical research study for individuals with Obsessive-Compulsive Disorder (OCD) at Hofstra University’s Anxiety and Depression Treatment Program is seeking research participants.

The study will provide FREE psychological treatment (Exposure and Response Prevention – ERP) for those who qualify. Research has shown that ERP is the optimal treatment for OCD. The study involves 16 biweekly sessions for the duration of 8 weeks, and is open to individuals who:

  1. are 18 years of age or older
  2. suffer with  primarily contamination-related obsessions and compulsions
  3. have not experienced any changes in medication in the past 3 months
  4. are not currently involved in any other treatment (i.e., ERP, supportive, psychodynamic, etc.) or are willing to temporarily suspend current treatment for the duration of the study.

Interested individuals are welcome to contact the primary investigator, Jennifer Wilson, Doctoral Student in the Department of Psychology, at JenniferAWilson4@gmail.com.

Virtual Avatars May Impact Real-World Behavior

February 12, 2014 by  
Filed under Research

How you represent yourself in the virtual world of video games may affect how you behave toward others in the real world, according to new research published in Psychological Science, a journal of the Association for Psychological Science.

“Our results indicate that just five minutes of role-play in virtual environments as either a hero or villain can easily cause people to reward or punish anonymous strangers,” says lead researcher Gunwoo Yoon of the University of Illinois at Urbana-Champaign.

As Yoon and co-author Patrick Vargas note, virtual environments afford people the opportunity to take on identities and experience circumstances that they otherwise can’t in real life, providing “a vehicle for observation, imitation, and modeling.”

They wondered whether these virtual experiences — specifically, the experiences of taking on heroic or villainous avatars — might carry over into everyday behavior.

The researchers recruited 194 undergraduates to participate in two supposedly unrelated studies. The participants were randomly assigned to play as Superman (a heroic avatar), Voldemort (a villainous avatar), or a circle (a neutral avatar). They played a game for 5 minutes in which they, as their avatars, were tasked with fighting enemies. Then, in a presumably unrelated study, they participated in a blind taste test. They were asked to taste and then give either chocolate or chili sauce to a future participant. They were told to pour the chosen food item into a plastic dish and that the future participant would consume all of the food provided.

The results were revealing: Participants who played as Superman poured, on average, nearly twice as much chocolate as chili sauce for the “future participant.” And they poured significantly more chocolate than those who played as either of the other avatars.

Participants who played as Voldemort, on the other hand, poured out nearly twice as much of the spicy chili sauce than they did chocolate, and they poured significantly more chili sauce compared to the other participants.

A second experiment with 125 undergraduates confirmed these findings and showed that actually playing as an avatar yielded stronger effects on subsequent behavior than just watching someone else play as the avatar.

Interestingly, the degree to which participants actually identified with their avatar didn’t seem to play a role:

“These behaviors occur despite modest, equivalent levels of self-reported identification with heroic and villainous avatars, alike,” Yoon and Vargas note. “People are prone to be unaware of the influence of their virtual representations on their behavioral responses.”

The researchers hypothesize that that arousal, the degree to which participants are ‘keyed into’ the game, might be an important factor driving the behavioral effects they observed.

The findings, though preliminary, may have implications for social behavior, the researchers argue:

“In virtual environments, people can freely choose avatars that allow them to opt into or opt out of a certain entity, group, or situation,” says Yoon. “Consumers and practitioners should remember that powerful imitative effects can occur when people put on virtual masks.”

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For more information about this study, please contact: Gunwoo Yoon at gyoon3@illinois.edu.

The original research article can be found online.

SOURCE: Association for Psychological Science

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