Good Foods Boost Moods

New research reveals that some common foods enhance moods with a striking similarity to valproic acid, a widely used prescription mood-stabilizing drug.

“Molecules in chocolate, a variety of berries and foods containing omega-3 fatty acids have shown positive effects on mood. In turn, our studies show that some commonly used flavor components are structurally similar to valproic acid,” said Karina Martinez-Mayorga, Ph.D., leader of the research team, which presented its findings at a meeting of the American Chemical Society.

Valproic acid, which is sold under brand names such as Depakene, Depakote and Stavzor, is used to smooth out the mood swings of people with manic-depressive disorder and related conditions, she said.

“The large body of evidence that chemicals in chocolate, blueberries, raspberries, strawberries, teas and certain foods could well be mood-enhancers encourages the search for other mood modulators in food,” she added.

While people have recognized the mood-altering properties of food for years, Martinez-Mayorga’s team is looking to identify the chemical compounds that moderate mood swings, help maintain cognitive health, improve mental alertness and delay the onset of memory loss.

Her study involved the use of techniques associated with chemoinformatics ― the application of informatic methods to solve chemical problems ― to screen the chemical structures of more than 1,700 food ingredients for similarities to antidepressant drugs and other agents with reported antidepressant activity.

She noted her team plans to move from analyzing the database to actually testing the flavor/mood hypothesis experimentally. The end result may be dietary recommendations or new nutritional supplements with beneficial mood effects, she said.

“It is important to remember that just eating foods that may improve mood is not a substitute for prescribed antidepressive drugs,” Martinez-Mayorga cautioned.

She added that eating specific foods and living a healthful lifestyle can generally boost moods for people who don’t require medication.

Karina Martinez-Mayorga, Ph.D., who described research done while working at the Torrey Pines Institute for Molecular Studies, is now with the Chemistry Institute at the National Autonomous University of Mexico.

Source: The American Chemical Society

Strawberries dipped in chocolate photo by shutterstock.

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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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Cocoa May Slow Cognitive Impairment of Aging

If there is a more pleasurable way of staving off the cognitive impairment of aging than drinking cocoa, perhaps only red wine drinkers have found it.

Flavanols are naturally occurring antioxidants found in abundance in cocoa plants. They help the body deal with free radicals that trigger negative changes in body chemistry and help prevent blood clots.

Now, a new study led by Giovambattista Desideri, M.D., study lead author and associate professor of internal medicine and public health at the University of L’Aquila in Italy, suggests ingesting cocoa flavanols daily may improve mild cognitive impairment.

Experts say that more than six percent of people aged 70 years or older develop mild cognitive impairment (MCI) annually. Moreover, MCI can progress to dementia and Alzheimer’s disease.

Researchers say flavanols may aid brain health by protecting neurons from injury, enhancing metabolism, and facilitating neuronal interaction with the molecular structures responsible for memory. They are also found in tea, grapes, red wine and apples and have been associated with a decreased risk of dementia.

Indirectly, flavanols may help by improving brain blood flow.

In the study, 90 elderly participants with mild cognitive impairment were randomized to drink daily either 990 milligrams (high), 520 mg (intermediate) or 45 mg (low) of a dairy-based cocoa flavanol drink for eight weeks.

Researchers controlled participants’ diet to eliminate other sources of flavanols from foods and beverages other than the dairy-based cocoa drink.

Cognitive function was examined by neuropsychological tests of executive function, working memory, short-term memory, long-term episodic memory, processing speed and global cognition.

Researchers found:

• Scores significantly improved in the ability to relate visual stimuli to motor responses, working memory, task-switching and verbal memory for those drinking the high and intermediate flavanol drinks;
• Participants drinking daily higher levels of flavanol drinks had significantly higher overall cognitive scores than those participants drinking lower-levels;
• Insulin resistance, blood pressure and oxidative stress also decreased in those drinking high and intermediate levels of flavanols daily. Changes in insulin resistance explained about 40 percent of the composite scores for improvements in cognitive functioning.

“This study provides encouraging evidence that consuming cocoa flavanols, as a part of a calorie-controlled and nutritionally-balanced diet, could improve cognitive function,” Desideri said. However, he warns that the beneficial findings may have been influenced by a variety of factors.

“The positive effect on cognitive function may be mainly mediated (influenced) by an improvement in insulin sensitivity. It is yet unclear whether these benefits in cognition are a direct consequence of cocoa flavanols or a secondary effect of general improvements in cardiovascular function.”

Furthermore, the study population was generally in good health without known cardiovascular disease. Thus, it would not be completely representative of all mild cognitive impairment patients.

In addition, only some clinical features of mild cognitive impairment were explored in the study.

“Given the global rise in cognitive disorders, which have a true impact on an individual’s quality of life, the role of cocoa flavanols in preventing or slowing the progression of mild cognitive impairment to dementia warrants further research,” Desideri said.

“Larger studies are needed to validate the findings, figure out how long the positive effects will last and determine the levels of cocoa flavanols required for benefit.”

The research is reported in the American Heart Association’s journal Hypertension.

Source: American Heart Association

Woman drinking cocoa photo by shutterstock.

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, Depression Reduce Brain Volume Thanks to Genetic ‘Switch’

Scientists have known that stress and depression can cause the brain to retract or lose volume, a condition associated with both emotional and cognitive impairment. Now, a new study discovers why this occurs.

Yale scientists have found that the deactivation of a single genetic switch can instigate a cascading loss of brain connections in humans and depression in animal models.

Researchers say the genetic switch, known as a transcription factor, represses the expression of several genes that are necessary for the formation of synaptic connections between brain cells. The loss of connections, in turn, can contribute to loss of brain mass in the prefrontal cortex, say the scientists.

“We wanted to test the idea that stress causes a loss of brain synapses in humans,” said senior author Ronald Duman, Ph.D. “We show that circuits normally involved in emotion, as well as cognition, are disrupted when this single transcription factor is activated.”

In the study, the research team analyzed tissue of depressed and non-depressed patients donated from a brain bank and looked for different patterns of gene activation.

The brains of patients who had been depressed exhibited lower levels of expression in genes that are required for the function and structure of brain synapses.

Lead author and postdoctoral researcher H.J. Kang, Ph.D., discovered that at least five of these genes could be regulated by a single transcription factor called GATA1.

When the transcription factor was activated in animal models, rodents exhibited depressive-like symptoms, suggesting GATA1 plays a role not only in the loss of connections between neurons but also in symptoms of depression.

This finding of genetic variations in GATA1 may help researchers identify people at high risk for major depression or sensitivity to stress.

“We hope that by enhancing synaptic connections, either with novel medications or behavioral therapy, we can develop more effective antidepressant therapies,” Duman said.

Source: Yale University

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

Genetic Link Found to Rapid Weight Gain from Antipsychotic Meds

Scientists have discovered two genetic variants associated with substantial, rapid weight gain occurring in nearly half of patients treated with antipsychotic medications.

The results from two studies from the Centre for Addiction and Mental Health in Canada could eventually be used to identify which patients have the variations, enabling doctors to choose strategies to prevent this serious side effect and offer more personalized treatment, the researchers note.

“Weight gain occurs in up to 40 percent of patients taking medications called second-generation or atypical antipsychotics, which are used because they’re effective in controlling the major symptoms of schizophrenia,” said Dr. James Kennedy, senior author of the study.

The weight gain can lead to obesity, type 2 diabetes, heart problems and a shortened life span, he noted.

“Identifying genetic risks leading to these side effects will help us prescribe more effectively,” said Kennedy. Currently, the center screens for two other genetic variations that affect patients’ responses to psychiatric medications.

Each study identified a different variation near the melanocortin-4 receptor (MC4R) gene, which is known to be linked to obesity.

In the latest study, people carrying two copies of a variant gained about three times as much weight as those with one or no copies, after six to 12 weeks of treatment with atypical antipsychotics.

The study had four patient groups: Two from the U.S., one in Germany, and one from a larger European study. Three of the four groups had never taken atypical antipsychotics.

Different groups were treated with drugs such as olanzapine, risperidone, aripiprazole or quetiapine, and compliance was monitored to ensure the treatment regime was followed, the researchers said. Weight and other metabolic-related measures were taken at the start and during treatment.

“The weight gain was associated with this genetic variation in all these groups, which included pediatric patients with severe behavior or mood problems, and patients with schizophrenia experiencing a first episode or who did not respond to other antipsychotic treatments,” noted researcher Dr. Daniel Müller.

“The results from our genetic analysis combined with this diverse set of patients provide compelling evidence for the role of this MC4R variant. Our research group has discovered other gene variants associated with antipsychotic-induced weight gain in the past, but this one appears to be the most compelling finding thus far.”

The gene’s role in antipsychotic-induced weight gain was identified in a study published earlier this year in The Pharmacogenomics Journal. Researchers
found a different variation on MC4R that was linked to the side effect.

For both studies, CAMH researchers did genotyping experiments to identify the single changes to the sequence of the MC4R gene — known as single nucleotide polymorphisms (SNPs) — related to the drug-induced weight gain side effect.

The MC4R gene encodes a receptor involved in the brain pathways regulating weight, appetite and satiety. “We don’t know exactly how the atypical antipsychotics disrupt this pathway, or how this variation affects the receptor,” said Müller. “We need further studies to validate this result and eventually turn this into a clinical application.”

The recent study is published online in the Archives of General Psychiatry.

Source: The Centre for Addiction and Mental Health (CAMH)

DNA photo by shutterstock.

Animal Study Suggests New Class of Antioxidants May Be Beneficial for Parkinson’s

A new powerful class of antioxidants may provide relief from Parkinson’s in the future.

The medication, called synthetic triterpenoids, blocked development of Parkinson’s disease in an animal model.

The trial is discussed in the journal Antioxidants & Redox Signaling , as authored by Dr. Bobby Thomas, a neuroscientist at the Medical College of Georgia.

Thomas and his colleagues were able to block the death of dopamine-producing brain cells that occurs in Parkinson’s by using the drugs to bolster Nrf2, a natural antioxidant and inflammation fighter.

Researchers know that stressors from a variety of sources, be it trauma, insect bites or the simple aging process increases oxidative stress causing the body to respond with inflammation — as a part of the natural healing process.

“This creates an environment in your brain that is not conducive for normal function,” Thomas said.

“You can see the signs of oxidative damage in the brain long before the neurons actually degenerate in Parkinson’s.”

Nrf2, the master regulator of oxidative stress and inflammation, is – inexplicably – significantly decreased early in Parkinson’s. In fact, Nrf2 activity declines normally with age.

“In Parkinson’s patients you can clearly see a significant overload of oxidative stress, which is why we chose this target,” Thomas said. “We used drugs to selectively activate Nrf2.”

Researchers looked at a number of antioxidants already under study for a wide range of diseases from kidney failure to heart disease and diabetes, and found triterpenoids to be the most effective on Nrf2.

Co-author Dr. Michael Sporn, Professor of Pharmacology, Toxicology and Medicine at Dartmouth Medical School, chemically modified the agents so they could permeate the protective blood-brain barrier.

Researchers found that in both human neuroblastoma and mouse brain cells they were able to document an increase in Nrf2 in response to the synthetic triterpenoids.

Their preliminary evidence indicates the synthetic triterpenoids also increase Nrf2 activity in astrocytes, a brain cell type which nourishes neurons and hauls off some of their garbage.

The drugs didn’t protect brain cells in an animal where the Nrf2 gene was deleted, more proof that that Nrf2 is the drugs’ target.

Researchers are now studying the impact of synthetic triterpenoids in an animal model genetically programmed to acquire PD slowly, as humans do.

Source: Medical College of Georgia