| The Memory Issue | Autumn 2008 |
Perish the Thought Forgetfulness isn’t usually something we welcome. People with post-traumatic stress disorder (PTSD), however, can find persistent memories of past trauma so overwhelming that they have difficulty functioning in the present. For these people, says Roger Pitman, an HMS professor of psychiatry and director of the PTSD Psychophysiology Laboratory at MGH, weakening selected memories may be just what the doctor ordered. Once called battle fatigue and shell shock, PTSD is now considered an anxiety disorder that can develop not just in combat veterans, but also in survivors of rape, childhood abuse, car accidents, and other traumatizing occurrences. These memories are easy to acquire: Most of us can recall where we were and what we were doing on September 11, 2001, far more vividly than the events of September 10, 2001. The challenge, Pitman says, is how to tame seemingly indelible traumatic memories. The answers to this puzzle may lie within the brain itself. Research suggests neurotransmitters released from the brainstem during stress play a key role in emotional memory. People with PTSD have been found to have lower-than-normal levels of cortisol and higher-than-average levels of noradrenaline, a ratio that may enhance learning and memory. This chemical pattern appears to improve the transfer of traumatic events from short-term into long-term memories, a process known as consolidation. In people with PTSD, says Pitman, “the emotional arousal and biological and neurological changes that accompany trauma may burn memories of the event into the brain so deeply that they keep coming back.” When traumatic memories resurface—triggered by a sound, smell, or other stimulus associated with the initial event—they may create additional biochemical changes that engrave them in the brain more deeply. This recall and repetition of the original memory is called reconsolidation. It, in turn, may lead to a greater likelihood the memories will resurface. This biochemical process may help explain why even the most successful therapeutic approach to PTSD—cognitive behavioral therapy—yields lasting symptomatic improvement in only about half of those who receive it. Researchers elsewhere have conducted experiments designed to quell PTSD at the cellular level in rats. Consolidation builds—and reconsolidation maintains—connections between neurons that are mediated by a protein. In an attempt to prevent reconsolidation, researchers injected stressed rats with anisomycin, a drug that inhibits the synthesis of this protein. Rats given anisomycin after trauma showed less fear when exposed to stimuli. Pitman’s laboratory has been studying how pharmaceuticals affect memory consolidation and reconsolidation in humans. In one noteworthy trial, Pitman and his colleagues gave the beta-blocker propranolol to 18 people who arrived at an emergency department following a trauma. The anti-adrenaline drug replaced anisomycin, which is too toxic for human use. “There’s evidence that a certain level of adrenergic activity is required for memories to be consolidated,” explains Pitman. “Because propranolol can block adrenergic activity, it might also interfere with memory consolidation.” The results were stunning: The treatment group received just a ten-day course of propranolol, beginning within six hours of the traumatizing event. Three months later, participants listened to audiotapes in which they described their initial trauma. People with PTSD typically have strong psychophysiological responses during this procedure: sweating, muscle twitches, accelerated heart rate. Yet subjects who had received propranolol didn’t show such physiological responses, compared with 23 controls. “From that,” says Pitman, “we inferred that their traumatic memories had been weakened.” His team’s findings made headlines, with reports trumpeting the promise of an effective new PTSD treatment. But critics expressed alarm that obliterating memories might prevent people from working through trauma and, worse, eliminate what it means to be human. Such concerns, suggests Pitman, are premature. His findings didn’t show that traumatic memories had been erased altogether, but rather dulled. “We have yet to encounter a person to whom we’ve given propranolol who says, ‘I don’t remember the trauma at all anymore,’ ” he says. And despite the Hollywood comparisons, none of his subjects’ other memories are erased. “People wonder what would occur if they were in our lab talking about their trauma and they thought about their dog,” he says. “Would they end up forgetting their dog? We don’t have nearly that power.” In fact, Pitman stresses that his results, while promising, are preliminary. He hopes to further our knowledge with additional research. His team recently received a large grant from the U.S. Department of Defense to investigate about a dozen drugs with the potential to inhibit memory reconsolidation in animals and humans. If the research is successful, says Pitman, such pharmaceuticals “may someday provide an alternate and potentially more efficacious way of treating PTSD.” Jessica Cerretani is assistant editor for the Harvard Medical Alumni Bulletin. Photocollage: ©iStockphoto.com |
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