Tuesday, 9 December 2014

gut microbiome and mental health


http://journals.lww.com/co-psychiatry/Fulltext/2015/01000/The_gut_microbiome_and_diet_in_psychiatry___focus.2.aspx


Monday, 18 August 2014

motivation and schizophrenia

l: Brain defect traps schizophrenics in twilight zone

Date:
August 17, 2014
Source:
University of Sydney
Summary:
People with schizophrenia struggle to turn goals into actions because brain structures governing desire and emotion are less active and fail to pass goal-directed messages to cortical regions affecting human decision-making, new research reveals.

People with schizophrenia struggle to turn goals into actions because brain structures governing desire and emotion are less active and fail to pass goal-directed messages to cortical regions affecting human decision-making, new research reveals.
Published in Biological Psychiatry, the finding by a University of Sydney research team is the first to illustrate the inability to initiate goal-directed behaviour common in people with schizophrenia.
The finding may explain why people with schizophrenia have difficulty achieving real-world goals such as making friends, completing education and finding employment.
"The apparent lack of motivation in schizophrenic patients isn't because they lack goals or don't enjoy rewards and pleasure," says the University of Sydney's Dr Richard Morris, the study's lead author. "They enjoy as many experiences as other people, including food, movies and scenes of natural beauty.
"What appears to block them are specific brain deficits that prevent them from converting their desires and goals into choices and behaviour."
Using a control group research design, the researchers used a two-prong approach to reveal how and why schizophrenics fail to convert their preferences into congruent choices.
First, using a series of experiments involving choosing between different snack food rewards, experimenters revealed that:
  • schizophrenic subjects had a liking for snack foods equivalent to healthy adults
  • when researchers reduced the value of one of the snacks, both subjects and healthy adults subsequently preferred different snacks, as expected
  • surprisingly, schizophrenic subjects had major difficulty choosing their preferred snack when provided with a choice between their preferred snack and the devalued snack.
Second, researchers used functional magnetic resonance imaging (fMRI) to measures brain activity while study subjects performed learning tasks involving snack foods. This technique relies on the fact that cerebral blood flow and neuronal activity are coupled.
When an area of the brain is in use, bloodflow to that region increases, thereby indicating neural activity. This neural activity can be presented graphically by colour-coding the strength of activation across the brain or in specific brain regions. The technique can localise neural activity to within millimetres.
Functional MRI results revealed the following:
  • schizophrenic subjects had normal neural activity in the brain region responsible for decision-making (prefrontal cortex)
  • among schizophrenic subjects, brain regions responsible, in part, for controlling actions and choice (the caudate) had far lower neural activity than in healthy subjects
  • lower neural activity in the caudate regions was correlated with the difficulty that schizophrenic subjects' had applying their food preferences to obtain future snack foods.
"Pathology in the caudate and associated brain regions may prevent schizophrenic subjects from properly evaluating their desires then transmitting that information to guide their behavior," says Dr Morris.
"This means that desires and goals are intact in people with schizophrenia, however they have difficulty choosing the right course of action to achieve those goals.
"This failure to integrate desire with action means people with schizophrenia are stuck in limbo, wanting a normal life but unable to take the necessary steps to achieve it."
Schizophrenia affects one per cent of people worldwide, including in Australia. However so-called "poor motivation" in schizophrenia is a major economic concern because it is not treated by current medicines, and often means patients fail to finish their education or hold a full-time job.

Gut bacteria and mind

Do gut bacteria rule our minds?

Do gut bacteria rule our minds?
This image illustrates the relationship between gut bacteria and unhealthy eating. Credit: Courtesy of UC San Francisco
It sounds like science fiction, but it seems that bacteria within us—which outnumber our own cells about 100-fold—may very well be affecting both our cravings and moods to get us to eat what they want, and often are driving us toward obesity.
In an article published this week in the journalBioEssays, researchers from UC San Francisco, Arizona State University and University of New Mexico concluded from a review of the recent scientific literature that microbes influence human eating behavior and dietary choices to favor consumption of the particular nutrients they grow best on, rather than simply passively living off whatever nutrients we choose to send their way.
Bacterial species vary in the nutrients they need. Some prefer fat, and others sugar, for instance. But they not only vie with each other for food and to retain a niche within their ecosystem—our digestive tracts—they also often have different aims than we do when it comes to our own actions, according to senior author Athena Aktipis, PhD, co-founder of the Center for Evolution and Cancer with the Helen Diller Family Comprehensive Cancer Center at UCSF.
While it is unclear exactly how this occurs, the authors believe this diverse community of microbes, collectively known as the  microbiome, may influence our decisions by releasing signaling molecules into our gut. Because the gut is linked to the immune system, the endocrine system and the nervous system, those signals could influence our physiologic and behavioral responses.
"Bacteria within the gut are manipulative," said Carlo Maley, PhD, director of the UCSF Center for Evolution and Cancer and corresponding author on the paper." "There is a diversity of interests represented in the microbiome, some aligned with our own dietary goals, and others not."
Fortunately, it's a two-way street. We can influence the compatibility of these microscopic, single-celled houseguests by deliberating altering what we ingest, Maley said, with measurable changes in the microbiome within 24 hours of diet change.
"Our diets have a huge impact on microbial populations in the gut," Maley said. "It's a whole ecosystem, and it's evolving on the time scale of minutes."
There are even specialized bacteria that digest seaweed, found in humans in Japan, where seaweed is popular in the diet.
Research suggests that  may be affecting our eating decisions in part by acting through the vagus nerve, which connects 100 million  from the digestive tract to the base of the brain.
"Microbes have the capacity to manipulate behavior and mood through altering the neural signals in the vagus nerve, changing taste receptors, producing toxins to make us feel bad, and releasing chemical rewards to make us feel good," said Aktipis, who is currently in the Arizona State University Department of Psychology.
In mice, certain strains of bacteria increase anxious behavior. In humans, one clinical trial found that drinking a probiotic containing Lactobacillus casei improved mood in those who were feeling the lowest.
Maley, Aktipis and first author Joe Alcock, MD, from the Department of Emergency Medicine at the University of New Mexico, proposed further research to test the sway microbes hold over us. For example, would transplantation into the gut of the bacteria requiring a nutrient from seaweed lead the human host to eat more seaweed?
The speed with which the microbiome can change may be encouraging to those who seek to improve health by altering microbial populations. This may be accomplished through food and supplement choices, by ingesting specific  in the form of probiotics, or by killing targeted species with antibiotics. Optimizing the balance of power among bacterial species in our gut might allow us to lead less obese and healthier lives, according to the authors.
"Because microbiota are easily manipulatable by prebiotics, probiotics, antibiotics, fecal transplants, and dietary changes, altering our microbiota offers a tractable approach to otherwise intractable problems of obesity and unhealthy eating," the authors wrote.
The authors met and first discussed the ideas in the BioEssays paper at a summer school conference on evolutionary medicine two years ago. Aktipis, who is an evolutionary biologist and a psychologist, was drawn to the opportunity to investigate the complex interaction of the different fitness interests of microbes and their hosts and how those play out in our daily lives. Maley, a computer scientist and evolutionary biologist, had established a career studying how tumor cells arise from normal cells and evolve over time through natural selection within the body as cancer progresses.
In fact, the evolution of tumors and of bacterial communities are linked, points out Aktipis, who said some of the bacteria that normally live within us cause stomach cancer and perhaps other cancers.
"Targeting the microbiome could open up possibilities for preventing a variety of disease from obesity and diabetes to cancers of the gastro-intestinal tract. We are only beginning to scratch the surface of the importance of the microbiome for human health," 

Saturday, 26 April 2014

Emotions

from Derek Bownds
Training emotions - a brief video from The Brain Club

I received an email recently from "The Brain Club" pointing me to the series of brief video presentations they are developing over time. I thought the presentation by Amit Etkin at Stanford Univ. was very effective. I'm including that video in this post. It describes the results of a meta-analysis of many papers that shows that in anxious and depressed individuals the brain's amygdala, insula, and cingulate are over-reactive while the prefrontal cortex is under-reactive. (i.e. the downstairs is over-riding the upstairs of our brains.) Cognitive training exercises available on the web that reinforce a positivity bias and enhance working memory lessen this upstairs/downstairs imbalance, and a brief review by Subramaniam and Vinogradov shows MRI data indicating that it is accompanied by enhancement of medial prefrontal activity.

 
Here is a slightly larger version of the figure from the meta-analysis paper showing the downstair (yellow) and upstairs (blue) regions whose activity changes with training.

A more through summary of cognitive training for impaired neural systems can be found in Vinogradov et al.

Thursday, 2 January 2014

Compulsive eating and addiction

Scripps Research Study Shows Compulsive Eating Shares Same Addictive Biochemical Mechanism with Cocaine, Heroin Abuse
The Research Provides New Clues to Obesity Epidemic
JUPITER, FL, March 23, 2010 –In a newly published study, scientists from The Scripps Research Institute have shown for the first time that the same molecular mechanisms that drive people into drug addiction are behind the compulsion to overeat, pushing people into obesity.
The new study, conducted by Scripps Research Associate Professor Paul J. Kenny and graduate student Paul M. Johnson, was published March 28, 2010 in an advance online edition of the journal Nature Neuroscience.
The study's startling findings received widespread publicity after a preliminary abstract was presented at a Society for Neuroscience meeting in Chicago last October. Articles heralding the new discovery appeared in news publications around the world, focusing on the point obese patients have been making for years – that, like addiction to other substances, junk food binging is extremely difficult to stop.
The study goes significantly further than the abstract, however, demonstrating clearly that in rat models the development of obesity coincides with a progressively deteriorating chemical balance in reward brain circuitries. As these pleasure centers in the brain become less and less responsive, rats quickly develop compulsive overeating habits, consuming larger quantities of high-calorie, high-fat foods until they become obese. The very same changes occur in the brains of rats that overconsume cocaine or heroin, and are thought to play an important role in the development of compulsive drug use.
Kenny, a scientist at Scripps Research's Florida campus, said that the study, which took nearly three years to complete, confirms the "addictive" properties of junk food.
The new study, unlike our preliminary abstract, explains what happens in the brain of these animals when they have easy access to high-calorie, high-fat food," said Kenny. "It presents the most thorough and compelling evidence that drug addiction and obesity are based on the same underlying neurobiological mechanisms. In the study, the animals completely lost control over their eating behavior, the primary hallmark of addiction. They continued to overeat even when they anticipated receiving electric shocks, highlighting just how motivated they were to consume the palatable food."
The scientists fed the rats a diet modeled after the type that contributes to human obesity—easy-to-obtain high-calorie, high-fat foods like sausage, bacon, and cheesecake. Soon after the experiments began, the animals began to bulk up dramatically.
"They always went for the worst types of food," Kenny said, "and as a result, they took in twice the calories as the control rats. When we removed the junk food and tried to put them on a nutritious diet – what we called the 'salad bar option' – they simply refused to eat. The change in their diet preference was so great that they basically starved themselves for two weeks after they were cut off from junk food. It was the animals that showed the "crash" in brain reward circuitries that had the most profound shift in food preference to the palatable, unhealthy diet. These same rats were also those that kept on eating even when they anticipated being shocked."
Lethally Simple
What happens in addiction is lethally simple, Kenny explained. The reward pathways in the brain have been so overstimulated that the system basically turns on itself, adapting to the new reality of addiction, whether its cocaine or cupcakes.
"The body adapts remarkably well to change—and that's the problem," said Kenny. "When the animal overstimulates its brain pleasure centers with highly palatable food, the systems adapt by decreasing their activity. However, now the animal requires constant stimulation from palatable food to avoid entering a persistent state of negative reward".
After showing that obese rats had clear addiction-like food seeking behaviors, Johnson and Kenny next investigated the underlying molecular mechanisms that may explain these changes. They focused on a particular receptor in the brain known to play an important role in vulnerability to drug addiction and obesity—the dopamine D2 receptor. The D2 receptor responds to dopamine, a neurotransmitter that is released in the brain by pleasurable experiences like food or sex or drugs like cocaine. In cocaine abuse, for example, the drug alter the flow of dopamine by blocking its retrieval, flooding the brain and overstimulating the receptors, something that eventually leads to physical changes in the way the brain responds to the drug.
The new study shows that the same thing happens in junk food addiction.
"These findings confirm what we and many others have suspected," Kenny said, "that overconsumption of highly pleasurable food triggers addiction-like neuroadaptive responses in brain reward circuitries, driving the development of compulsive eating. Common mechanisms may therefore underlie obesity and drug addiction."
Consistent with common mechanisms explaining addiction and obesity, levels of the D2 dopamine receptors were significantly reduced in the brains of the obese animals, similar to previous reports of what happens in human drug addicts, Kenny noted. Remarkably, when the scientists knocked down the receptor using a specialized virus, the development of addiction-like eating was dramatically accelerated.
This addiction-like behavior happened almost from the moment we knocked down the dopamine receptors," Kenny noted. "The very next day after we provided access to the palatable food, their brains changed into a state that was consistent with an animal that had been overeating for several weeks. The animals also became compulsive in their eating behaviors almost immediately. These data are, as far as we know, the strongest support for the idea that overeating of palatable food can become habitual in the same manner and through the same mechanisms as consumption of drugs of abuse."
The study, "Addiction-Like Reward Dysfunction and Compulsive Eating in Obese Rats: Role for Dopamine D2 Receptors," was supported by a Bank of America Fellowship, The Margaret Q. Landenberger Research Foundation and the National Institutes of Health.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Scripps Florida is located in Jupiter, Florida.