May 2, 2008
NIH Podcast Episode #0057
Balintfy: Welcome to the 57th episode of NIH Research Radio with news about the ongoing medical research at the National Institutes of Health--the nation's medical research agency. . I'm your host Joe Balintfy. Coming up in this episode: how a brain study may lead to improved epilepsy treatments; and an interview about Alzheimer’s Disease. But first, a report on how past child abuse and genes could result in PTSD risk for adults. That's next on NIH Research Radio.
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Past Child Abuse and Genes Could Result in PTSD Risk for Adults
Balintfy: Posttraumatic stress disorder, or PTSD, is an anxiety disorder that can develop after exposure to a terrifying event or ordeal in which grave physical harm occurred or was threatened. New research reveals that depending on genetics and childhood experiences, some may be more susceptible to PTSD. Wally Akinso reports.
Akinso: A traumatic event is much more likely to result in posttraumatic stress disorder in adults who experienced trauma in childhood, but scientists have found that certain gene variations raise risk considerably if the childhood trauma involved physical or sexual abuse.
Insel: Scientists who were involved in this study from Emory University in Atlanta tried to understand how much of PTSD is genetic and how much of it is due to the environment.
Akinso: Dr. Thomas Insel is the Director of the National Institute of Mental Health.
Insel: Now obviously because we call it posttraumatic stress disorder there's some environmental factor here, because you develop this after traumatic stress. But not everybody develops PTSD after a traumatic stress and so the question that these investigators were asking was-why does some people develop PTSD and others who may have the same or either a greater amount of stress don't seem to show the consequence of PTSD afterwards.
Akinso: The NIMH study suggests that early-life abuse can result in particularly potent changes to the stress response system as it develops-depending partly on whether or not the variations are present in the gene. Dr. Insel says the findings can help researchers learn which prevention and treatment strategies are likely to work best for each person.
Insel: This is a finding that needs to be replicated. If replicated it would become one of many factors that we try to put together as a kind of biosignature. That would say-if we know about these 5, 10, maybe 20 genetic variations that increase the risk for PTSD in someone who has a particular kind of personal history that those are the people that we might really want focus on to try to preempt PTSD after something like military service or after a bad car accident or after a traumatic event of any kind in adulthood.
Akinso: Dr. Insel believes that by untangling the complex interactions between genetic variations and environmental factors then scientists could possibly predict more accurately who's at risk of disorders like PTSD. This is Wally Akinso at the National Institutes of Health Bethesda, Maryland.
A Brain Study May Lead To Improved Epilepsy Treatments
Balintfy: Epilepsy is a brain disorder that causes people to have recurring seizures. The seizures happen when clusters of nerve cells in the brain, called neurons, send out the wrong signals. There is no cure for epilepsy, but medicines can control
In this report, Wally Akinso explains how researchers continue to search for better treatments.
Akinso: A brain study may lead to improved epilepsy treatments.
Miller: We’re interested in increasing the efficacy of central nervous system acting drugs in epilepsy.
Akinso: Dr. David Miller is the Principal Investigator in the Laboratory of Pharmacology at the National Institute of Environmental Health Sciences. He explains that there are two problems with epilepsy drugs:
Miller: One is variable responses by patients to these drugs. So physicians will often have to change drugs in the course of therapy and second problem is 30 percent of epileptics don’t respond to any of the drugs and that makes it very difficult.
Akinso: Because the drugs only work sometimes with some people, Dr. Miller asked the question—what is it about the way the brain works?
Miller: And one of the theories that have been in the literature for a long time is that it’s the blood brain barrier preventing these drugs from getting from the blood into the central nervous system.
Akinso: The blood-brain barrier, which resides in brain capillaries, is a limiting factor in treatment of many central nervous system disorders. It is altered in epilepsy so that it no longer permits free passage of administered antiepileptic drugs into the brain. Using a rodent model of epilepsy, researchers found one of the body’s own neurotransmitters released during seizures turns on a signaling pathway in the brain that increases production of a protein that could reduce medication entry into the brain. Dr. Miller said their work identifies the way seizures increase production of a drug-transport protein in the blood brain barrier.
Miller: Within the blood-brain barrier, there are these transporters, the major one being P-glycoprotein and they basically kick drugs back into the circulation and don’t permit them to get into the central nervous system. So the hypothesis we tested was that if you could manipulate P-glycoprotein expression in the blood-brain barrier you could improve pharmacal therapy for epilepsy patients.
Akinso: Dr. Miller said targeting blood-brain barrier signals that increase P-glycoprotein expression suggests a promising way to improve the effectiveness of drugs that are used to treat epilepsy, though more research is needed before new therapies can be developed.
Miller: This is a new way of looking at pharmacal therapy. What we’re doing basically is using the blood-brain barrier’s own signaling system to repress changes that make it harder for the drugs to get in. In essence what we have is some sort of combination therapy we’re proposing. One that hits the signaling system and the second one that goes into the brain after the signaling system is hit and gets into the targets in the neurons, which is where the antiepileptic drugs are working.
Akinso: He added that these findings provide insight into one mechanism that underlies drug resistance in epilepsy and possibly other central nervous system disorders. This is Wally Akinso at the National Institutes of Health, Bethesda, Maryland.
Balintfy: When we come back, an in-depth interview about Alzheimer’s disease. Stay tuned.
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Balintfy: With May being Older Americans Month, we’re taking a look at a disease that affecting more and more people: Alzheimer’s. Dr. Nina Silverberg is the assistant director of the Alzheimer’s disease centers program at the National Institute on Aging here at NIH. We started by asking what exactly is AD?
Silverberg: AD is a brain disease. It’s associated with aging, but it’s not a normal part of aging. It affects memory and thinking and behavior. It’s more common in people as they get older. So like I said it is associated with aging, but it’s not a normal part of aging. The disease starts, what we think, with is damage to the brain without any outward symptoms a person would know about. And that’s really considered the earliest stages. A little bit later there’s something that now diagnosed mild cognitive impairment, MCI, and that is not dementia but at that point people are experiencing some forgetting and a large number of people who have been diagnosed with MCI will go on to develop AD within some number of years, not immediately. And then as the disease progresses, there are basically three stages that are usually referred to: mild, moderate and severe. And in the milder stages, people are pretty much able to maintain most aspects of their daily life perfectly fine. You could have a conversation with a person with AD and not really even know that they had it. And then in the more moderate stages, people will start behaving inappropriately sometimes, or forgetting much more, repeating the same questions over and over, or stories over and over. And in the more severe stages, they will lose the ability to control their bodily functions. They really need complete care at that point.
Balintfy: how long can a person live with AD?
Silverberg: The average is 8 to 10 years but people can live quite a long time after they’re diagnosed with the disease. And unfortunately, towards the end, they’re really unable to take care of themselves at all. My grandmother had AD and she lived with it for 14 years before she passed away. So it can get quite difficult at the end.
Balintfy: What tips would you offer for people who might be facing AD or have someone in their family facing the disease?
Silverberg: I think the main concern is safety. The Alzheimer’s Association has a wonderful program called Safe Return where they actually give the person with Alzheimer’s disease a bracelet they can wear that has identifying information. And they have a system set up where they can contact local law enforcement. Wandering is one of the earlier symptoms of the disease, not the earliest, but people tend to get lost, unfortunately and they might not realize where they are even when they are in what should be a familiar area. And because of that, families worry a lot when their loved one gets lost and so the safe return program is one good option.
The other one that I think is important is for the caregiver because care giving for AD, especially as it gets worse and worse. Sometimes people don’t realize how much more they’re taking on because it happens slowly. And people can end up extremely stressed without realizing anything has changed over time. The Alzheimer’s Association has support groups and information about respite care that can really help the caregiver. Helping yourself as a caregiver is very important to helping the person who has the disease.
Balintfy: How many Americans are affected by AD?
Silverberg: There’s an estimate that it affects 4.5 million Americans currently – that’s a large number. And with the baby-boom generation getting older, we expect, unfortunately, more and more cases of it to be coming up.
Balintfy: What is some of the latest research telling us about AD?
Silverberg: There are a lot of different approaches being taken currently. There are observations studies looking at lifestyle, activity, how active a person is, what they’re eating, to see if there are any connections between those things and whether or not people contract AD. We’re also conducting genetic research to look at people who do have it and people who don’t and see if we can find out any more information about genetic associations. There’s also some very interesting work on imaging, brain scans. We have now developed compounds that will stick to some of the proteins that are involved with AD. It looks like those compounds are able to show us who has the disease and who doesn’t. It’s still in the early stages of research, but it may even be able to show us who’s going to develop AD, which would be very helpful for the other area of research I was going to mention: clinical trials. We do have many different types of medications, some of which are over the counter, which are being looked at to see if they can either help delay the onset or prevent AD.
Balintfy: Thanks to Dr. Nina Silverberg from the National Institute on Aging. For more information about AD, visit www.nia.nih.gov/alzheimers.
Balintfy: And that’s it for this episode of NIH Research Radio. Please join us again on Friday, May 16th when our next edition will be available for download. I'm your host, Joe Balintfy. Thanks for listening.
NIH Research Radio is a presentation of the NIH Radio News Service, part of the News Media Branch, Office of Communications and Public Liaison in the Office of the Director at the National Institutes of Health in Bethesda, Maryland, an agency of the US Department of Health and Human Services.