Monday 5 November 2012

The Fear Factor, chemical bravery


Fear is an emotion induced by a perceived threat that causes animals to move quickly away from the location of the perceived threat, and sometimes hide. It is a basic survival mechanism occurring in response to a specific stimulus, such as pain or the threat of danger. In short, fear is the ability to recognize danger leading to an urge to confront it or flee from it (also known as the fight-or-flight response) but in extreme cases of fear (horror and terror) a freeze or paralysis response is possible.
The brain structure that is the center of most neurobiological events associated with fear is the amygdala, located behind the pituitary gland. The role of the amygdala in fear is best understood as part of a circuitry of fear learning. It is essential for proper adaptation to stress and specific modulation of emotional learning and memory. In the presence of a threatening stimulus, the amygdala generates the secretion of hormones that influence fear and aggression. Once response to the stimulus in the form of fear or aggression commences, the amygdala may elicit the release of hormones into the body to put the person into a state of alertness, in which they are ready to move, run, fight, etc. This defensive response is generally referred to in physiology as the fight-or-flight response regulated by the hypothalamus.

Exposure therapy is a behavioural therapy technique in which people with phobias, in a limited and structured manner, are exposed to their fears after being shown different relaxation and coping techniques, aimed at decreasing the intensity of their fear response. In a study, to prepare the participants for the exposure, they were given educational materials about exposure therapy and instructions on how to cope with their former avoidance strategies during the pre-treatment assessment. However, no cognitive behavioural techniques such as breathing or relaxation techniques were used.

Cortisol is a stress hormone released from the adrenal gland. It has many functions, including increasing blood sugar, but it is also thought to affect learning and memory processes. Cortisol is a type of hormone called a glucocorticoid. Previous animal research using other glucocorticoid hormones has shown them to be effective at promoting ‘extinction processes’ (lessening of fear during exposure to a fear-inducing stimulus). Therefore, the researchers wanted to see whether glucocorticoids could be useful in enhancing exposure therapy in humans.
The participants were given three sessions of exposure therapy using virtual exposure to heights. Virtual reality exposure to heights has been shown to be effective for treating people with acrophobia.
One hour before each session, half the participants were given a cortisol pill, while the other half were given a placebo pill. Neither the participants nor the person giving them the pills knew which pills were placebos. Three to five days after the last treatment session, the participants had a post-treatment session and were assessed once more a month later. These post-treatment assessments were compared to assessments made before the treatment had commenced. The success of the treatment was assessed by giving the participants questionnaires in which they were asked to rate how fearful they felt when considering 20 situations that could cause fear of heights.
This study shows that cortisol treatment prior to virtual reality exposure therapy sessions for acrophobia can have a beneficial effect compared to placebo with virtual reality exposure. The researchers also point out that virtual reality-based exposure therapy for fear of heights has been shown to be effective.
Alturnatively the Pentagon is spending up to $11 million at three medical research institutions with the hope that D-Cycloserine (DCS) can be used to get rid of fearful and horrific memories.
Experts at Emory University, the University of Southern California and New York-Presbyterian/Weill Cornell Medical Center will study the effectiveness of D-Cycloserine (DCS). DCS is a pharmaceutical thought to help extinguish fearful memories. It’s usually taken right before exposure therapy, a process that involves recalling traumatic experiences in an effort to nullify the menacing associations that accompany them.
Researchers will look at two different kinds of exposure therapy: Virtual reality, where a patient is fully immersed in digital combat scenarios, and prolonged imaginal exposure therapy, which asks them to simply remember and recount fearful memories. A total of 300 patients, all of them veterans from Iraq and Afghanistan, will partake. They’ll undergo seven individual weekly sessions of one of the therapies. Before each session, half will receive DCS, and the rest will get a placebo. Experts have already spent plenty of time figuring out how DCS works. It’s been around since the 1960s, when it was used to treat tuberculosis. Now, however, researchers are more excited about the drug’s potential ability to alleviate symptoms of depression, schizophrenia, obsessive-compulsive disorder and, of course, PTSD — without a lifetime of pill-popping.
DCS seems to enhance the brain’s learning process. For PTSD treatment, the drug could, ostensibly, help patients more quickly internalize that, say, driving down a suburban American highway is far different  and less dangerous than driving on a Baghdad street. The drug also binds to receptors in the amygdala, the region of the brain that governs fear response. So by blocking out fearful reactions while a patient revisits trauma, experts think DCS can, literally, “extinguish” fear right at the source. Emory researchers have already tried using DCS and virtual reality in humans with PTSD, fear of heights and obsessive compulsive disorder. Since 2006, Rothbaum and a team of experts have been comparing exposure therapy, used along with DCS, Xanax or placebo, in patients. “Results so far are positive,” Rothbaum says, though they haven’t finished analyzing the data.
That said, results from some other human studies on DCS aren’t encouraging. Several disappointing trials using DCS were presented by researchers assembled at the International Society for Traumatic Stress Studies conference. The Pentagon previously tried to treat PTSD with “illicit” substances, like marijuana and ecstasy, thus far have been cancelled.
The research team will also be conducting genetic tests on every patient. In particular, they’ll be looking at a gene dubbed “BDNF.” Experts already know that a variant of the BDNF gene can make fear extinction tougher. By comparing patient results to genes, Rothbaum says they hope to “figure out what’s the best treatment approach, and whether DCS can really rescue those patients, where maybe therapy alone can’t.” Of course, the idea of using drugs to tweak memories isn’t without controversy: An online debate flared last year among two camps of neurologists and neuroethicists, arguing over whether the existence of such drugs would “alter something that makes us all human”.
Then again, those debates hinge on DCS, or some other memory extinguisher, actually working. DCS’s efficacy is far from proven. And earlier research efforts that tested supposed “fear-extinguishing” drugs, most notably a series of much-touted, Pentagon-funded studies on Propanolol at Harvard, have all been disappointments.
Its still early days for a chemical pill to change our perception of what fear is, the danger is that the normal checks and balances that makes us safe could also change our personalities. Although it could be potentially useful in a combat situation or for Post traumatic syndrome . A chemical solution is not the best answer. But considering PTSD afflicts at least 250,000 of this generation’s soldiers, it might be helpful to find any solution at all...


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