الأحد، 24 يناير 2016

عقار لعلاج الخوف



CONTRIBUTING OP-ED WRITER
A Drug to Cure Fear

Richard A. Friedman JAN. 22, 2016 COMMENT
Photo
CreditJillian Tamaki


RECENT COMMENTS

SEE ALL COMMENTS 
WRITE A COMMENT
Email
Share
Tweet
Save
More


WHO among us hasn’t wanted to let go of anxiety or forget about fear? Phobias, panic attacks and disorders like post-traumatic stress are extremely common: 29 percent of American adults will suffer from anxiety at some point in their lives.

Sitting at the heart of much anxiety and fear is emotional memory — all the associations that you have between various stimuli and experiences and your emotional response to them. Whether it’s the fear of being embarrassed while talking to strangers (typical of social phobia) or the dread of being attacked while walking down a dark street after you’ve been assaulted (a symptom of PTSD), you have learned that a previously harmless situation predicts something dangerous.

It has been an article of faith in neuroscience and psychiatry that, once formed, emotional memories are permanent. Afraid of heights or spiders? The best we could do was to get you to tolerate them, but we could never really rid you of your initial fear. Or so the thinking has gone.

The current standard of treatment for such phobias revolves around exposure therapy. This involves repeatedly presenting the feared object or frightening memory in a safe setting, so that the patient acquires a new safe memory that resides in his brain alongside the bad memory. As long as the new memory has the upper hand, his fear is suppressed. But if he is re-traumatized or re-exposed with sufficient intensity to the original experience, his old fear will awaken with a vengeance.

This is one of the limitations of exposure therapy, along with the fact that it generally works in only about half of the PTSD patients who try it. Many also find it upsetting or intolerable to relive memories of assaults and other traumatizing experiences.

We urgently need more effective treatments for anxiety disorders. What if we could do better than creating a new safe memory — and actually get rid of emotions attached to the old bad one?

New research suggests that it may be possible not just to change certain types of emotional memories, but even to erase them. We’ve learned that memories are uniquely vulnerable to alteration at two points: when we first lay them down, and later, when we retrieve them.

Merel Kindt, a professor of psychology at the University of Amsterdam, and her colleagues have seemingly erased the emotional fear response in healthy people with arachnophobia. For a study published last month in the journal Biological Psychiatry, she compared three groups made up of 45 subjects in total. One group was exposed to a tarantula in a glass jar for two minutes, and then given a beta-blocker called propranolol that is commonly prescribed to patients for performance anxiety; one was exposed to the tarantula and given a placebo; and one was just given propranolol without being shown the spider, to rule out the possibility that propranolol by itself could decrease spider fear.Photo
CreditJillian Tamaki

Dr. Kindt assessed the subjects’ anxiety when they were shown the spider the first time, then again three months later, and finally after a year. What she found was remarkable. Those who got the propranolol alone and those who got the placebo had no improvement in their anxiety. But the arachnophobes who were exposed to the spider and given the drug were able to touch the tarantula within days and, by three months, many felt comfortable holding the spider with their bare hands. Their fear did not return even at the end of one year.




How does this work? Well, propranolol blocks the effects of norepinephrine in the brain. This chemical, which is similar to adrenaline, enhances learning, so blocking it disrupts the way a memory is put back in storage after it is retrieved — a process called reconsolidation.

Arachnophobes have an emotional memory that involves an association between spiders and a dreaded outcome, like a spider bite. This “fear memory” is the source of their phobia — even if (as is often the case) it never actually happened. The basic idea is that when Dr. Kindt briefly exposed the subjects to the spider, she reactivated their fear, which made the fear memory susceptible to the influence of propranolol.

Reconsolidation is a bit like pulling up a file on your computer, rewriting the same material in a bigger, bolder font and saving it again. Disrupting reconsolidation with propranolol or another drug is akin to retrieving this document, erasing some or all of the text and then writing something new in its place.

Dr. Kindt is not the first to demonstrate that disrupting reconsolidation can weaken or erase emotional memories. Several studies of rats done in 2000 showed that a drug called anisomycin, which blocks the synthesis of proteins in the brain, could reduce fear associations. In one, researchers taught rats to fear a sound by pairing it with a shock. After the animals were fear-conditioned, they were presented with the sound and then immediately given the drug. When the animals were exposed to the sound again, they no longer appeared afraid; they had forgotten their original fear.

Curiously, there is a very narrow time window after retrieving a fear memory when you can disrupt that memory — hours, in the animal studies — before it closes and the drug has no effect.


These studies suggest that someday, a single dose of a drug, combined with exposure to your fear at the right moment, could free you of that fear forever. But there’s a flip side to this story about how to undo emotional learning: how to strengthen it. We can do that with drugs as well, and may have been doing it for some time.

ANXIETY enhances emotional memory. We all know that — it’s why you can easily forget where you put your wallet, but will never forget being attacked. This is the case because anxiety leads to the release of norepinephrine in the brain, which, again, strengthens emotional learning. It is also why we should think twice about casually prescribing stimulants like Ritalin and Adderall for young people who really don’t need them. Stimulants also cause the release of norepinephrine and may enhance fear learning. So it is possible that taking stimulants could increase one’s risk of developing PTSD when exposed to trauma.

Indeed, a study that will be published next month found that the escalating use of stimulants by the military in active duty soldiers, including those serving in Iraq and Afghanistan, was strongly correlated with an increase in the rates of PTSD, even when controlling for other factors, like the rate of attention deficit hyperactivity disorder. The study examined the use of prescription stimulants, like Ritalin and Adderall, and the rates of PTSD in nearly 26,000 military service members between 2001 and 2008, and found that the incidence of PTSD increased along with the prescriptions.







By blocking the effect of norepinephrine and disrupting memory reconsolidation, we could perhaps reverse this process. The clear implication of these studies is that emotional memory is not permanent after all.

Before you rush off into a panic about the dystopian possibility of mind control or memory deletion, it’s important to recognize that the procedure in Dr. Kindt’s study only weakened the subjects’ fear memory and avoidant behavior. Although the procedure is able to alter or perhaps delete the fear memory (something exposure therapy cannot do), it does nothing to the factual, or biographical, memory, which remains intact.

This is not “Eternal Sunshine of the Spotless Mind,” the movie in which a dysfunctional couple decides to erase their memories of each other and start their lives all over again. To the contrary, you still remember your biography, but your fear would be stripped of its force. The subjects knew perfectly well after the study that they previously feared spiders and that they now — strangely — felt little to no anxiety around them.


If this new approach is effective in other anxiety disorders, like PTSD, you would expect someone who was assaulted in his home to remember the attack perfectly well, but no longer feel afraid of being at home. What’s so bad about that?


It would certainly be superior to exposure therapy, which is far from a permanent fix. Once, while on vacation in Costa Rica, I was standing next to a young man on a zip line platform in a rain forest when he began to hyperventilate. I learned that he had a fear of heights and had had exposure treatment a year before, which he felt had fixed the problem. But now, his old fear was triggered and he was having a full-blown panic attack. I suppose he was lucky to be stuck with a psychiatrist in the jungle; I talked him down the ladder to the ground.

How effective this new memory-disrupting approach will be in treating more serious anxiety disorders like PTSD or panic is unclear. A few preliminary studies using propranolol in PTSD showed mixed results. Some found no effect, but a 2015 review of PTSD treatment studies published in Biological Psychology found that propranolol administered with six brief trauma reactivation sessions significantly improved PTSD symptoms compared with a placebo.

Study results may well change with the development of better methods for administering propranolol or new drugs that are more effective in disrupting memory reconsolidation. Marieke S. Tollenaar, a psychologist at Leiden University in the Netherlands who has studied the effects of propranolol on memory, told me that the “final test” would be to “examine in real life whether propranolol in addition to standard exposure treatment procedures would be beneficial. Little has been done there yet; most work is still done experimentally in the lab.”

Some may view any attempt to tamper with human memory as disturbing because it seems at odds with what we ought to do as a culture with the darker aspects of our history: Never alter the facts, even if we have divergent interpretations of them. And it is critical not to destroy places where crimes of humanity and collective trauma took place, like the concentration camps, so we never forget what we have done and remain capable of doing. Fair enough. But I see no reason not to help frightened individuals soften their painful emotional memories.







Some may also argue that it’s a mistake to tinker with our fear responses because they’re natural — they evolved this way for a reason. Like most other animals, we come hard-wired with a flight or fight response along with its associated anxiety and fear. Without this warning system to protect us from predators and other dangers, we’d have been dinner long ago on the savanna.

But what was once adaptive millions of years ago isn’t always so helpful today. People who suffer panic attacks hyperventilate and have an intense desire to flee in situations where there is rarely actual danger. It turns out that panic disorder is associated with an increased sensitivity to carbon dioxide in the brain. If you lived in a cave with a clan of hominid fire-dwellers, you’d have been one of the first to get out when the oxygen supply was dwindling.

Curiously, that might help explain why some people have panic attacks that wake them at night. These patients don’t panic during so-called REM sleep, when dreams occur, but during non-REM sleep, when they are deeply relaxed, when breathing slows, and the levels of carbon dioxide rise, generating a false suffocation alarm.

Evolutionary design has left us a few million years out of date; we are hard-wired for a Paleolithic world, but have to live in a modern one. The irrational fear of anxiety disorders was once probably useful and lifesaving. No longer.

But maybe that modern world can help. I see nothing wrong with doing all we can to rid ourselves of pathological anxiety, including using drugs to alter our painful emotional memories.
Correction: January 22, 2016 


An earlier version of this article incorrectly described some of the details of a study. Arachnophobes who were given a drug and exposed to a tarantula were able to touch the spider four days later, not hold them in a jar on Day 1.


Richard A. Friedman is a professor of clinical psychiatry and the director of the psychopharmacology clinic at the Weill Cornell Medical College, and a contributing opinion writer.


Follow The New York Times Opinion section on Facebook and Twitter, and sign up for the Opinion Today newsletter.
مرسلة بواسطة في

ليست هناك تعليقات:

إرسال تعليق

الاشتراك في: تعليقات الرسالة (Atom)