Prozac May Have Antiviral Properties

The antidepressant fluoxetine (Prozac) appears to have antiviral properties, especially against human enteroviruses — a group of more than 60 viruses that includes poliovirus.

Researchers at the University of California, Los Angeles discovered the unexpected property while conducting laboratory tests on cell cultures.

Although immunization has kept poliovirus under control around the world, other enteroviruses remain a primary cause of certain types of meningitis, encephalitis, conjunctivitis, and several other diseases. 

Second only to the common cold virus, enteroviruses cause an estimated 15 million infections each year in the U.S., according to the Centers for Disease Control and Prevention.

Currently there are no treatments for enterovirus infections, and physicians can only offer supportive care and allow an infection to run its course.

An effective antiviral would be able to prevent millions of sicknesses annually, said the UCLA researchers. Vaccines are most effective if the immune system is taught to recognize and attack a virus. But enteroviruses have so much genetic variety that it would be too difficult to create a vaccine to prevent them.

So, in search for antiviral properties, the researchers turned to high-throughput screening (HTS), a method that allows scientists to test tens of thousands of chemical compounds in a single day using robotics.

The group recruited Dr. Robert Damoiseaux, the scientific director of UCLA’s Molecular Screening Shared Resource (MSSR), who specializes in HTS. Together they tested a collection of approved drugs and other chemical compounds and discovered several compounds that restrain enterovirus production.

Surprisingly, fluoxetine stood out from the crowd. In a series of follow-up tests, the researchers found that fluoxetine interferes with the growth and replication of coxsackieviruses, a prominent subtype of enteroviruses.

The researchers repeated the experiment on several kinds of coxsackieviruses with recurring success. Without the ability to reproduce, these invading viruses simply would die off.

Yet even with all this evidence, taking Prozac may not be the best way to clear a viral infection.

“We do not yet understand the mechanism of action, and we do not yet have any proof of antiviral effectiveness in humans or animals,” said lead researcher Paul Krogstad, M.D., professor of molecular and medical pharmacology.

Also, fluoxetine is linked to an increased risk of internal bleeding, and so too are some enteroviruses. The extra risk of hemorrhaging could possibly worsen the infection.

Krogstad said his group needs to gain a better understanding of how, exactly, fluoxetine stops viral reproduction. Overall, these findings could open the door to new drugs that target viral replication without the side effects of Prozac.

Source:  Antimicrobial Agents and Chemotherapy

 

Prozac pill bottle photo by shutterstock.

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Young Adults Value Appearance More Than Health

For many young adults, beauty really is little more than skin-deep and has little to do with health.

A new investigation by University of Missouri researchers studied how college-age women view their bodies, and how they feel about media messages aimed at women.

María Len-Ríos, Ph.D., an associate professor of strategic communication, and Suzanne Burgoyne, Ph.D., a professor of theater, used a focus group to develop an interactive play about body image.

The objective of the interactive play was to encourage frank discussions about conflicting societal messages regarding weight, values and healthful choices.

“During our focus group conversations, we learned that young people don’t think about nutrition when it comes to eating,” Len-Ríos said. “They think more about calorie-counting, which isn’t necessarily related to a balanced diet.”

The focus groups included college-age women, college-age men and mothers of college-age women, who discussed how body image is associated with engaging in restrictive diets, irregular sleep patterns and over-exercising.

“We receive so many conflicting media messages from news reports and advertising about how we should eat, how we should live and how we should look,” Len-Ríos said. “Some participants said they realize images of models are digitally enhanced, but it doesn’t necessarily keep them from wanting to achieve these unattainable figures—this is because they see how society rewards women for ‘looking good.’”

During the course of the investigation, researchers completed in-depth interviews with nutritional counselors who said lack of time and unhealthy food environments can keep college-age students from getting good nutrition.

“Eating well takes time, and, according to health professionals, college students are overscheduled and don’t have enough time to cook something properly or might not know how to prepare something healthful,” Len-Ríos said.

Based on the focus group conversations and interviews, Carlia Francis, an MU theater doctoral student and playwright, developed “Nutrition 101,” a play about women’s body images.

During performances, characters divulge their insecurities about their own bodies, disparage other women’s bodies and talk about nutrition choices. After a short, scripted performance, the actors remain in character, and audience members ask the characters questions.

“When you’re developing something for interactive theater, focus groups and in-depth interviews are great at getting at stories,” Len-Ríos said.

“Many of the stories used in the interactive play—like valuing people because of their appearance and not their personal qualities or abilities—came from individuals’ personal experiences.”

Burgoyne said the play helps facilitate dialogues about nutrition, media messages and self-awareness.

“Body image is a sensitive topic, and the play helps open discussions about how individuals view themselves and how media messages influence their self-images,” Burgoyne said.

“An easy way to improve individuals’ body images does not exist, but hopefully, the conversations that arise from the performances will help develop ways to counteract the images that the media promote.”

Source: University of Missouri

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How Drugs for Schizophrenia Sow Seeds of Resistance

A new study has identified why certain drugs have mixed success in treating schizophrenia; effective at first, but with chronic administration becoming less and less so.

In the study, reported online in the journal Nature Neuroscience, scientists investigated the external genetic reasons (called epigenetic factors) that cause treatment-resistance to atypical antipsychotic drugs.

Use of antipsychotic drugs is the standard of care for schizophrenia. Researchers at Mount Sinai School of Medicine report that 30 percent of individuals with schizophrenia do not respond to currently available treatments.

Researchers 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, Ph.D., lead investigator on the study.

Researchers 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.

In response, the research team administered a chemical called suberoylanilide hydroxamic acid (SAHA), which inhibits the entire family of HDACs. 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 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, Ph.D., 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 the frontal cortex of individuals with schizophrenia, which then reduces the presence of mGlu2, and thereby limits the efficacy of these drugs.”

As a result of these findings, Gonzalez-Maeso’s team is now developing compounds that specifically inhibit HDAC2 as adjunctive treatments to antipsychotics.

Source:The Mount Sinai Hospital/Mount Sinai School of Medicine

Stress Changes Learning in the Brain

A new experiment from German scientists suggests stress invokes our brain to use different and more complex processes during learning.

In the study, cognitive psychologists Drs. Lars Schwabe and Oliver Wolf discovered that the presence or absence of stress is associated with use of different brain regions and different strategies in the learning process.

Stress appears to make the brain work harder and use a more complex approach when learning. Study findings are reported in the Journal of Neuroscience.

Researchers discovered that non-stressed individuals applied a deliberate learning strategy, while stressed subjects relied more on their gut feeling.

“These results demonstrate for the first time that stress has an influence on which of the different memory systems the brain turns on,” said Schwabe.

In the study researchers analyzed the data from 59 subjects. Two groups were assigned with one group asked to immerse one hand into ice-cold water for three minutes (while being observed by video surveillance).

As expected, this activity stressed the subjects with data collected and confirmed by hormone assays.

The other group was asked to immerse one of their hands in warm water. Then both the stressed and non-stressed individuals completed a task called weather prediction. The task involved having subjects look at playing cards with different symbols and then using the cards to predict which combinations of cards forecast rain and which sunshine.

Each combination of cards was associated with a certain probability of good or bad weather. People apply differently complex strategies in order to master the task.

During the weather prediction task, the researchers recorded the brain activity with MRI.

Researchers found that both stressed and non-stressed subjects learned to predict the weather according to the symbols. However, the way in which they learned the task varied.

Non-stressed participants focused on individual symbols and not on combinations of symbols. They consciously pursued a simple strategy.

The MRI data showed that they activated a brain region in the medial temporal lobe – the hippocampus, which is important for long-term memory.

Stressed subjects, on the other hand, applied a more complex strategy.

They made their decisions based on the combination of symbols. They did this, however, subconsciously, i.e. they were not able to formulate their strategy in words.

In this group of stress participants, brain scans showed that the so-called striatum in the mid-brain was activated — a brain region that is responsible for more unconscious learning.

“Stress interferes with conscious, purposeful learning, which is dependent upon the hippocampus,” concluded Schwabe. “So that makes the brain use other resources. In the case of stress, the striatum controls behavior — which saves the learning achievement.”

Source: Ruhr-University Bochum

Abstract of the brain with key photo by shutterstock.

Regular Use of Computer Program Improves Seniors’ Memory

A new study by UCLA researchers finds that regular use of computerized memory and language training can help seniors.

Age-related memory decline affects approximately 40 percent of older adults. The cognitive decline is characterized by self-perception of memory loss and a decline in memory performance.

This was one of the first studies to assess the cognitive effects of a computerized memory training program. Researchers found that dedicated use of the program significantly improved memory and language skills among older adults.

In the study, researchers followed 59 participants with an average age of 84. Participants were recruited from local retirement communities.

Seniors were divided into two groups. The first group used a brain fitness program for an average of 73, 20-minute sessions, over a six-month period; the second group performed 45 20-minute sessions times during the same period.

The first group demonstrated significantly higher improvement in memory and language skills, compared to the second group.  Researchers said the study’s findings confirm that brain fitness tools may help improve language and memory.

Experts say that computer-aided training may ultimately help protect individuals from the cognitive decline associated with aging and Alzheimer’s disease.

Previous studies have shown that engaging in mental activities can help improve memory, but little research has been done to determine whether the numerous brain fitness games and memory training programs on the market are effective in improving memory.

Source: UCLA

Elderly woman on a computer photo by shutterstock.

Virtual Simulations Help Train Psychologists, Psychiatrists

Following on the heels of flight simulation training, medical simulation and now virtual mental health simulations train health professionals by realistically mimicking patient symptoms.

New simulators mimic the symptoms of a patient with clinical psychological disorders, according to new research presented at the American Psychological Association’s 120th Annual Convention.

“As this technology continues to improve, it will have a significant impact on how clinical training is conducted in psychology and medicine,” said psychologist and virtual reality technology expert Albert “Skip” Rizzo, Ph.D.

Technological advances including artificial intelligence and expert systems allow a highly interactive interaction with simulators even allowing the simulators to carry on a conversation with real humans.

“This has set the stage for the ‘birth’ of intelligent virtual humans to be used in clinical training settings,” Rizzo said. He showed videos of clinical psychiatry trainees engaging with virtual patients called “Justin” and “Justina.”

Justin is a 16-year-old with a conduct disorder who is being forced by his family to participate in therapy. Justina, the second and more advanced iteration of this technology, is a sexual assault victim who was designed to have symptoms of post-traumatic stress disorder.

In an initial test, 15 psychiatry residents, of whom six were women, were asked to perform a 15-minute interaction with Justina.

Video of one such interaction shows a resident taking an initial history by asking a variety of questions. Programmed with speech recognition software, Justina responds to the questions and the resident is able to make a preliminary diagnosis.

Rizzo’s virtual reality laboratory is working on the next generation of virtual patients using information from this and related user tests, and will further modify the characters for military clinical training, which the U.S. Department of Defense is funding, he said.

Researchers are working to develop simulated or virtual veterans with depression and suicidal thoughts, for use in training clinicians and other military personnel how to recognize the risk for suicide or violence.

Over time, Rizzo hopes to create a comprehensive computer training module that has a diverse library of virtual patients with numerous “diagnoses” for use by psychiatric and psychology educators and trainees.

Currently, psychology and psychiatry students are trained by role-playing with other students or their supervisors to gain experience to treat patients. They then engage in supervised on-the-job training with real patients to complete their degrees.

“Unfortunately, we don’t have the luxury of live standardized ‘actor’ patients who are commonly used in medical programs, so we see this technology as offering a credible option for clinical psychology training,” he said.

“What’s so useful about this technology is novice clinicians can gain exposure to the presentation of a variety of clinical conditions in a safe and effective environment before interacting with actual patients. In addition, virtual patients are more versatile and can be available anytime, anywhere. All you need is a computer.”

Source: American Psychological Association

Increased Dopamine Can Reduce Impulsivity

Researchers have discovered that elevating the level of the neurotransmitter dopamine in the frontal lobe of the brain can significantly decrease impulsivity in healthy adults.

The finding is important as impulsiveness is a risk factor for substance abuse.

“Impulsivity is a risk factor for addiction to many substances, and it has been suggested that people with lower dopamine levels in the frontal cortex tend to be more impulsive,” said lead author Andrew Kayser, Ph.D.

Researchers from the Ernest Gallo Clinic and Research Center at the University of California, San Francisco performed a double-blinded placebo study. The study has been published in the Journal of Neuroscience.

In the research, 23 adult research participants were given either tolcapone, a medication approved by the Food and Drug Administration (FDA) that inhibits a dopamine-degrading enzyme, or a placebo.

Investigators then gave the participants a task that measured impulsivity, asking them to make a hypothetical choice between receiving a smaller amount of money immediately (“smaller sooner”) or a larger amount at a later time (“larger later”).

Each participant was tested twice, once with tolcapone and once with placebo.

More impulse (at baseline) participants were more likely to choose the less impulsive “larger later” option after taking tolcapone than they were after taking the placebo.

Magnetic resonance imaging conducted while the participants were taking the test confirmed that regions of the frontal cortex associated with decision-making were more active in the presence of tolcapone than in the presence of placebo.

“To our knowledge, this is the first study to use tolcapone to look for an effect on impulsivity,” said Kayser.

The study is a proof-in-concept investigation and was not designed to investigate the reasons that reduced dopamine is linked with impulsivity.

However, explained Kayser, scientists believe that impulsivity is associated with an imbalance in dopamine between the frontal cortex, which governs executive functions such as cognitive control and self-regulation, and the striatum, which is thought to be involved in the planning and modification of more habitual behaviors.

“Most, if not all, drugs of abuse, such as cocaine and amphetamine, directly or indirectly involve the dopamine system,” said Kayser.

“They tend to increase dopamine in the striatum, which in turn may reward impulsive behavior. In a very simplistic fashion, the striatum is saying ‘go,’ and the frontal cortex is saying ‘stop.’ If you take cocaine, you’re increasing the ‘go’ signal, and the ‘stop’ signal is not adequate to counteract it.”

Kayser and his research team plan a follow-up study of the effects of tolcapone on drinking behavior.

“Once we determine whether drinkers can safely tolerate this medication, we will see if it has any effect on how much they drink while they’re taking it,” said Kayser.

Currently, Tolcapone is approved as a medication for Parkinson’s disease — a disease in which a chronic deficit of dopamine inhibits movement.

Source: University of California – San Francisco