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We explore the groundbreaking efforts to advance autism research through postmortem brain tissue donation with David G. Amaral, professor of psychiatry and behavioral sciences. Learn how brain donation provides unique insights into the biological causes of autism and its co-occurring conditions, and discover how families can play a pivotal role in transforming our understanding of neurodevelopmental disorders.
David G. Amaral is a professor of psychiatry and behavioral sciences.
He discusses the KevinMD article, “Why talking to families of autistic individuals about brain donation is a priority.”
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Transcript
Kevin Pho: Hi, and welcome to the show. Subscribe at KevinMD.com/podcast. Today, we welcome David Amaral. He’s a professor of psychiatry and behavioral sciences. Today’s KevinMD article is “Why talking to families of autistic individuals about brain donation is a priority.” David, welcome to the show.
David Amaral: Thank you, Kevin.
Kevin Pho: Nice to be here. So let’s start by briefly sharing your story and journey.
David Amaral: Yeah, I’m a professor in the Department of Psychiatry and Behavioral Sciences at UC Davis. I’ve been here since about 1995. I’m trained as a neuroscientist and also have a degree in psychology. Prior to the early 2000s, I was doing brain research, trying to understand systems in the brain related to memory, to emotion, and to social behavior.
But I was actually recruited by families of autistic individuals to get involved in autism research. And then fortunately for me, a group of five families in the Sacramento area where UC Davis is based wanted to start a new institute dedicated to autism research and started the MIND Institute, which stands for Medical Investigation of Neurodevelopmental Disorders.
And I was fortunate to be asked to be the founding research director and then got very heavily involved in autism research and have been doing so ever since about 1998.
Kevin Pho: All right. Of course, you talk more about your research in your KevinMD article, “Why talking to families of autistic individuals about brain donation is a priority.” Tell us what this article is about for those who didn’t get a chance to read it.
David Amaral: Right. The article really asks clinicians, physicians, and others to consider if they have a family in their practice that has an autistic individual, or if they’re treating an autistic individual themselves, to bring up the issue of carrying out a donation of their brain following death.
It’s a difficult topic. We understand that. But what we realized probably more than 20 years ago is that, of course, autism is a behavioral disorder, but it is due to alterations in the structure and function of the brain. Yet we don’t really understand at this point what’s going on in the brains of autistic individuals, what changes have taken place.
What we know from other studies—neurological disorders like Alzheimer’s disease and Parkinson’s disease and others—is that a lot of the keys to understanding what the disorder is lies in studying postmortem brains. Alzheimer’s disease has been studied for more than 100 years, yet that hasn’t really taken place to the same extent, certainly in autism.
Really, the first postmortem neuropathological study wasn’t done until the 1980s, and we realized that as more and more awareness of autism was happening, and more and more scientists were getting involved in research, one of the problems was there just wasn’t enough postmortem brains to satisfy the need for doing first-rate research.
So we started Autism BrainNet. Autism BrainNet is a program of the Simons Foundation that’s based in New York City, and Autism BrainNet is set up to collect and preserve postmortem brains from autistic individuals and appropriate nonautistic individuals as comparisons. Then we make that tissue available to scientists worldwide.
We just celebrated our 10th anniversary, so we have been doing this for some time. We’ve collected about 400 donations, and about half of those are autistic brains, but autism is so heterogeneous that it really requires a very large number of donations. We don’t feel like we’re anywhere near that number at this point in time.
While we have the infrastructure set up to collect the brain, to preserve the brain, to provide clinical support to families, what we realized is that unless we get the word out to families of autistic individuals, they may not be aware that there is a need for postmortem brain donation. So that’s why we did the article with you, Kevin, and are trying to ramp up our outreach effort to bring the word to families of autistic members and autistic individuals within the U.S. and Canada, that this is really important—a very present need for pursuing autism research.
Kevin Pho: Can you tell us or give us an example of the types of questions that you’re trying to answer that requires postmortem autistic brains?
David Amaral: Very good question, Kevin. And, you know, there’s so much we don’t know about autism that there are a lot of questions that we are trying to answer. I’ll just give you a couple of examples. One that we’re making some headway on is the genetics of autism. So we understand from looking at blood samples of autistic individuals that there are probably something on the order of about 200 genes that, if they’re mutated, if there’s alterations of those genes, if they’re not functioning properly, increases the risk of having autism.
So autism is not a single-gene condition. There are many, many genes that seem to contribute. But what has been surprising in the last 10 years or so is that the genetics of autism that we understand from blood is only part of this story. It turns out that because the brain develops so rapidly prenatally and so many neurons are produced so rapidly, there are a lot of genetic errors that take place as the brain develops.
These can cause focal changes in the genetic architecture of the individual—it’s called somatic mutations, meaning that it’s not throughout the entire body, but it’s just located in one area of the body or of the brain. And it turns out that the somatic mutations that are now being studied in postmortem brains are more prevalent in autistic individuals than in individuals that don’t have autism.
So we think that by, again, by studying the postmortem brain, we will understand more about what genetic conditions lead to the behavioral alterations of autism. Again, that’s something where we know that is going to pan out, but we need to have additional postmortem brains in order to fully understand those genetic changes.
One area that really is just beginning to even be studied is the fact that if you have autism, it actually increases the risk for you having dementia as well—for having Alzheimer’s disease. And this is something where perhaps there’s one or two studies so far. There’s been epidemiological studies showing that people with autism are more likely, ultimately, to have a dementing illness, but we haven’t been able to look at the brains of older individuals with autism to see whether they have the hallmark features of Alzheimer’s disease as well.
So while Autism BrainNet initially was focusing on trying to obtain postmortem brain donations from younger individuals so we could understand the beginnings of the disorder, we are now beginning to focus increasingly on outreach to older individuals in order to look at this issue. Do autistic individuals show Alzheimer’s plaques and tangles earlier, or to a greater extent, than other individuals without autism? We simply don’t know because we haven’t been able to look. So that’s an example of why we’re, again, reaching out to clinicians to bring the idea of donation to their clients and raise the possibility.
One thing, Kevin, I wanted to make clear is that we never want to put pressure on a family to make a brain donation. This is certainly something that’s discretionary. But when you make a brain donation, the usefulness of the donation to science diminishes over time. So we like to have donations come into the Autism BrainNet facility within 24 to 48 hours after death.
What that means is that that’s not the time when you want to start thinking about this. It’s, you know, obviously we understand that it’s a traumatic time for families. It’s, you know, it’s a very difficult, sad time for families. And we encourage families to consider the possibility of making a brain donation much, much earlier when there’s obviously no urgency. And, you know, again, many families have made a donation because they want to see research done to help living individuals with autism. And we think that that will be the case. We think doing postmortem brain research will ultimately find some additional targets for interventions for treatment, but we encourage people to think about it ahead of time so that it just can be done very easily at the time of death.
Kevin Pho: Can you walk us through the process of an actual brain donation, and from start to finish, what exactly does that look like so patients can know what to expect?
David Amaral: Sure. So the first step is to, at the time of a death or even if a death is imminent, call our 24/7 hotline, which is 877-333-0999. That’s 877-333-0999. What will happen at that point in time is the family or the clinician helping the family will be put in contact with our clinical staff. The clinical staff will talk with them to determine whether the donation is appropriate.
If so, then our clinical staff will set up all of the processes necessary in order for the donation to be made. So there has to be a consent signed, for example, that the family will allow this to take place. At that point in time, then the clinical staff will arrange for a process where the brain can be recovered. Then the brain will be shipped to one of our three sites. We have sites in California, in Texas, and in Massachusetts. At that point in time, the brain is processed very quickly in order to preserve it in a pristine state and then to store it away. It’s put into a freezer so that it can be used for scientific studies. Those studies, I should point out, the way we process the brain, it can actually be used for decades. It’s good for scientific studies for a long period of time.
We make sure that the smallest amount of tissue goes to each investigator that wants some tissue so that not only can it be used for decades, but it can be studied by dozens, if not hundreds, of investigators as well. So we ensure that this precious gift is optimized for scientific evaluation.
After the donation is made, if the individual is autistic, our clinical staff will then speak with the family and try to get additional clinical information from the family about their characteristics. If they have any information—maybe the family member had participated in scientific studies—and we can get some of that information and put it into our database. All of this goes into a database that investigators can have access to. Of course, it’s anonymous; the names of the family or the individual are not provided to investigators, but we do provide them with information.
For example, about 30 to 40 percent of people with autism also have intellectual disability, and it’s important to know if you’re doing a scientific investigation whether that was the case or not. So all that information goes into our database, which then gets presented to investigators when they want to acquire some of this tissue. There is absolutely no cost to the family. The family can still have an open-casket funeral. So we try and make the whole process as simple and as positive as possible. And, you know, we get families that come back to us afterward and say, “We weren’t so sure about what was going to happen with the brain donation, but you guys have made this a really positive event.” And particularly, you know, many people with autism—unfortunately, the death occurs, for example, in the first time a teenager has a first grand mal seizure and there’s a death due to that. It was unexpected, and, you know, the family is reeling from this event, but they realize that by making a donation, something positive has come out of what was otherwise a tragic event.
So, again, that’s the process. The families are coached through every step along the way. If a physician or other practitioner knows of a family that may want to provide a brain donation, they can get in touch with us. We have an email and they can contact us. They can either use the 877 number to get information, or they can visit www.autismbrainnet.org and get information.
The last thing I wanted to say, Kevin, is that people might be asking—or clinicians and physicians might be asking—”Well, isn’t this the same thing as organ donation?” And it turns out it isn’t. So if you put on your driver’s license that you want to be an organ donor, that is for tissues that are going to be given to other living individuals, oftentimes life-saving—for example, heart donations, or lung, or kidney, or whatever. But that precludes brain donation—brain, obviously, we’re not doing brain transplants.
So you have to make it known to either family or your physician that you want to make a donation. Oftentimes, our donors are hospitalized, and it is a physician who calls us and says, “You know, I think that this family may want to make a donation to Autism BrainNet.” Really, the article and the fact that we’re doing this interview is to alert physicians that they can be very helpful in spreading the word of the need and the potential for making a postmortem brain donation for autistic individuals.
Kevin Pho: Now, for those clinicians who perhaps may not be as versed in discussing the potential donation of postmortem brains, what are some tips that you could give to facilitate that conversation in a sensitive manner?
David Amaral: I think what the physician can say is that there’s an organization that was started to help other autistic individuals, and what we do by acquiring postmortem brain tissue is to understand the disorder, understand what’s going on in the autistic brain, with a goal of ultimately finding targets to alleviate some of the challenges of autism.
Now, again, I want to make it clear to the clinicians and physicians who are listening to us that we’re not trying to cure or prevent autism per se, but 30 percent of autistics have epilepsy. We’ve found that nearly 70 percent of autistics have severe anxiety. Autistic individuals also have, you know, profound sleep disturbances and gastrointestinal problems, all of which we think stem from alterations of brain structure and function. It’s these kind of co-occurring debilitating conditions that we’re really trying to target through our research. So I think, you know, a physician can say there’s an organization that is dedicated to improving the quality of life of autistic individuals. They do so by studying the brain, and they make it easy to make a brain donation. I would suggest that physicians direct potential donors to our website, autismbrainnet.org. That’s autismbrainnet.org. And on our website, we have a families section that actually we call the Memories of Hope, where the families make testimonials to the donors. And if you read some of these, you’ll see that family members, by and large, find this to be a very positive experience. As I said, sometimes, you know, coming out of a tragedy, they think, “Why did this happen?” But by making a donation, they actually feel it’s a positive contribution they can make to the future of living autistic individuals.
So I think I would use some of those sort of stances in order to bring up the topic. It really is directed at improving the quality of life for living autistic individuals.
Kevin Pho: We’re talking to David Amaral. He’s a professor of psychiatry and behavioral sciences. Today’s KevinMD article is “Why talking to families of autistic individuals about brain donation is a priority.” David, let’s end with some take-home messages you want to leave with the KevinMD audience.
David Amaral: Thanks, Kevin. I appreciate taking the time to talk with you today. Again, I think you can have all the infrastructure in the world set up to collect postmortem brain donations, but if you don’t get the word out to families and to autistic individuals about the need for postmortem brain donations in order to improve the quality of life of autistic individuals, we won’t get the donations that are necessary. So again, we have only been able to touch some topics superficially here today, but I would recommend that physicians go to our website themselves, check us out, check out—there are articles that have used postmortem brain tissue to carry out research—if they’re interested in additional kinds of work that’s been done. But there’s a huge amount of information there, not only about how we’re organized, but the process of collecting brains, how we distribute tissue.
Kevin Pho: David, thank you so much for sharing your perspective and insight, and thanks again for coming on the show.
David Amaral: Thanks so much, Kevin. I appreciate it.
