In the brain, broken down ‘motors’ cause anxiety

When motors break down, getting where you want to go becomes a struggle. Problems arise in much the same way for critical brain receptors when the molecular motors they depend on fail to operate. Now, researchers reporting in Cell Reports, a Cell Press publication, on February 7, have shown these broken motors induce stress and anxiety in mice. The discovery may point the way to new kinds of drugs to treat anxiety and other disorders.

The study in mice focuses on one motor in particular, known as KIF13A, which, according to the new evidence, is responsible for ferrying serotonin receptors. Without proper transportation, those receptors fail to reach the surface of neurons and, as a result, animals show signs of heightened anxiety.

In addition to their implications for understanding anxiety, the findings also suggest that defective molecular motors may be a more common and underappreciated cause of disease.

"Most proteins are transported in vesicles or as protein complexes by molecular motors," said Nobutaka Hirokawa of the University of Tokyo. "As shown in this study, defective motors could cause many diseases."

Scientists know that serotonin and serotonin receptors are involved in anxiety, aggression, and mood. But not much is known about how those players get around within cells. When Hirokawa’s team discovered KIF13A at high levels in the brain, they wondered what it did.

The researchers discovered that mice lacking KIF13A show greater anxiety in both open-field and maze tests and suggest that this anxious behavior may stem from an underlying loss of serotonin receptor transport, which leads to a lower level of expression of those receptors in critical parts of the brain.

"Collectively, our results suggest a role for this molecular motor in anxiety control," the researchers wrote. Hirokawa says the search should now be on for anti-anxiety drug candidates aimed at restoring the brain’s serotonin receptor transport service.

Even the brains of people with anxiety states can get used to fear

Fear is a protective function against possible dangers that is designed to save our lives. Where there are problems with this fear mechanism, its positive effects are cancelled out: patients who have a social phobia become afraid of perfectly normal, everyday social situations because they are worried about behaving inappropriately or being thought of as stupid by other people. Scientists from the Centre for Medical Physics and Biomedical Technology and the University Department of Psychiatry and Psychotherapy at the MedUni Vienna have now discovered that this fear circuit can be deactivated, at least in part.

In a study by Ronald Sladky, led by Christian Windischberger (Centre for Medical Physics and Biomedical Technology), which has recently been published in the magazine PLOS One, functional magnetic resonance tomography was used to measure the changes in the brain activity of socially phobic patients and healthy test subjects while they were looking at faces. This experiment simulates social confrontation with other people without actually placing the individual in an intolerable situation of anxiety.

Permanent confrontation has a diminishing effect on anxiety
“The study demonstrated that people with social phobia initially exhibit greater activity in the amygdala and in the medial, prefrontal cortex of the brain, however after a few faces this activity recedes,” says Sladky. This contradicts the assumption made thus far that the emotional circuit of socially phobic individuals is unable to adapt adequately to this stress-inducing situation.

Permanent confrontation with the test task not only led to a solution to the “problem” being found more quickly among the patients with anxiety, but also to some areas of the brain being bypassed which otherwise were over-stimulated, a characteristic typical of anxiety. Says Sladky: “We therefore concluded that there are functional control strategies even in the emotional circuits of people with social phobia, although the mechanisms take longer to take effect in these individuals. The misregulation of these parts of the brain can therefore be compensated to a degree.”

These findings could, according to Sladky, provide a starting point for the development of personalised training programmes that will help affected individuals to conquer unpleasant situations in their everyday lives more effectively. In Austria, around 200,000 people a year are affected by some form of social phobia. The number of people who suffer this condition without seeking help for it is likely to be very high, since many affected individuals fail to seek assistance or do so only too late as a result of their anxiety.

Brain & Behavior Research Foundation Announces 10 Major Research Achievements of 2012

In 2012, the Brain & Behavior Research Foundation funded more than 200 new promising ideas through its NARSAD Grants to identify the causes, improve treatments and develop prevention strategies for mental illness. Many research projects also came to fruition in 2012, and the Foundation highlights ten significant findings.

A New Focus on the ‘Post’ in Post-Traumatic Stress

Psychological trauma dims tens of millions of lives around the world and helps create costs of at least $42 billion a year in the United States alone. But what is trauma, exactly?

Both culturally and medically, we have long seen it as arising from a single, identifiable disruption. You witness a shattering event, or fall victim to it — and as the poet Walter de la Mare put it, “the human brain works slowly: first the blow, hours afterward the bruise.” The world returns more or less to normal, but you do not.

In 1980, the Diagnostic and Statistical Manual of Mental Disorders defined trauma as “a recognizable stressor that would evoke significant symptoms of distress in almost everyone” — universally toxic, like a poison.

But it turns out that most trauma victims — even survivors of combat, torture or concentration camps — rebound to live full, normal lives. That has given rise to a more nuanced view of trauma — less a poison than an infectious agent, a challenge that most people overcome but that may defeat those weakened by past traumas, genetics or other factors.

Now, a significant body of work suggests that even this view is too narrow — that the environment just after the event, particularly other people’s responses, may be just as crucial as the event itself.

The idea was demonstrated vividly in two presentations this fall at the Interdisciplinary Conference on Culture, Mind and Brain at the University of California, Los Angeles. Each described reframing a classic model of traumatic experience — one in lab rats, the other in child soldiers.

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New research investigates how the common ‘cat parasite’ gets into the brain

The Toxoplasma gondii parasite causes toxoplasmosis. The parasite is common and infects between 30 and 50 per cent of the global population. It also infects animals, especially domestic cats. Human infection is contracted by eating poorly cooked (infected) meat and handling cat feces. Toxoplasmosis first appears with mild flu-like symptoms in adults and otherwise healthy people before entering a chronic and dormant phase, which has previously been regarded as symptom-free. But when the immune system is weakened toxoplasmosis in the brain can be fatal. The fetus can be infected through the mother and because of this risk, pregnant women are recommended to avoid contact with cat litter boxes. Surprisingly, several studies in humans and mice have suggested that even in the dormant phase, the parasite can influence increasing risk taking and infected people show higher incidence of schizophrenia, anxiety and depression, which are broader public health concerns.

In their recent study Fuks et al. showed for the first time how the parasite enters the brain and increases the release of a neurotransmitter called GABA (gaba-Aminobutyric acid), that, amongst other effects, inhibits the sensation of fear and anxiety. In one laboratory experiment, human dendritic cells were infected with toxoplasma. After infection, the cells, which are a key component of the immune defense, began actively releasing GABA), In another experiment on live mice, the team was able to trace the movement of infected dendritic cells in the body after introducing the parasite into the brain, from where it spread and continued to affect the GABA system.

"For toxoplasma to make cells in the immune defense secrete GABA was as surprising as it was unexpected, and is very clever of the parasite," says Antonio Barragan, researcher at the Center for Infectious Medicine at Karolinska Institute and the Swedish Institute for Communicable Disease Control. "It would now be worth studying the links that exist between toxoplasmosis, the GABA systems and major public health threats."

Autism severity may stem from fear

Most people know when to be afraid and when it’s ok to calm down.

But new research on autism shows that children with the diagnosis struggle to let go of old, outdated fears. Even more significantly, the Brigham Young University study found that this rigid fearfulness is linked to the severity of classic symptoms of autism, such as repeated movements and resistance to change.

For parents and others who work with children diagnosed with autism, the new research highlights the need to help children make emotional transitions – particularly when dealing with their fears.

“People with autism likely don’t experience or understand their world in the same way we do,” said Mikle South, a psychology professor at BYU and lead author of the study. “Since they can’t change the rules in their brain, and often don’t know what to expect from their environment, we need to help them plan ahead for what to expect.”

The complete study appears in the journal Autism Research.

Mediation Combined with Art Therapy Can Change Your Brain and Lower Anxiety

Cancer and stress go hand-in-hand, and high stress levels can lead to poorer health outcomes in cancer patients. The Jefferson-Myrna Brind Center of Integrative Medicine combined creative art therapy with a Mindfulness-based Stress Reduction (MBSR) program for women with breast cancer and showed changes in brain activity associated with lower stress and anxiety after the eight-week program. Their new study appears in the December issue of the journal Stress and Health.

Daniel Monti, MD, director of the Jefferson-Myrna Brind Center of Integrative Medicine and lead author on the study, and colleagues have previously published on the success of Mindfulness-based Art Therapy (MBAT) at helping cancer patients lower stress levels and improve quality of life.

“Our goal was to observe possible mechanisms for the observed psychosocial effects of MBAT by evaluating the cerebral blood flow (CBF) changes associated with an MBAT intervention in comparison with a control of equal time and attention,” says Monti. “This type of expressive art and meditation program has never before been studied for physiological impact and the correlation of that impact to improvements in stress and anxiety.”

Scientists identify depression and anxiety biomarker in youths

Scientists have discovered a cognitive biomarker – a biological indicator of a disease – for young adolescents who are at high risk of developing depression and anxiety. Their findings were published in the journal PLOS ONE.

The test for the unique cognitive biomarker, which can be done on a computer, could be used as an inexpensive tool to screen adolescents for common emotional mental illnesses.  As the cognitive biomarker may appear prior to the symptoms of depression and anxiety, early intervention (which has proven to be one of the most effective ways of combatting mental illness) could then be initiated.

For the study, 15-18 year old participants underwent genetic testing and environmental assessment, an exercise which would currently be too expensive and take too long to use as a widespread method of screening.  The adolescents were then given a computer test to gauge how they process emotional information. The test had the participants evaluate whether words were positive, negative or neutral (examples included ‘joyful’ for positive, ‘failure’ for negative, and ‘range’ for neutral).

Those adolescents with a variation of one gene (the short form of the serotonin transporter) as well as exposure to intermittent family arguments for longer than six months and violence between parents before the age of six were shown to have marked difficulty in evaluating the emotion within the words, indicating an inability to process emotional information. Previous research associated a maladjusted perception and response to emotions, as seen here, with a significantly increased risk of depression and anxiety.

Professor Ian Goodyer, Principal Investigator on the study from the University of Cambridge, said:  “Whether we succumb to anxiety and depression depends in part on our tendencies to think well or poorly of ourselves at troubled times. How it comes about that some people see the ‘glass half full’ and think positively whereas other see the ‘glass half empty’ and think negatively about themselves at times of stress is not known.

The evidence is that both our genes and our early childhood experiences contribute to such personal thinking styles. Before there are any clinical symptoms of depression or anxiety, this test reveals a deficient ability to efficiently and effectively perceive emotion processes in some teenagers – a biomarker for low resilience which may lead to mental illnesses.”