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Thinning Brain Cortex May Signal Depression
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Thinning Brain Cortex May Signal Depression

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Thinning Brain Cortex May Signal Depression
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IRA FLATOW, host:

Up next, a new study that links changes in brain structure to depression. For decades, researchers at the New York State Psychiatric Institute have been studying the children and the grandchildren of people with major, debilitating depression to see if the offspring would develop the disease, too.

And as part of that work, the scientists did brain scans. They did MRIs of the brains of 131 people, some with, some without a family history of depression. They wanted to see if the brains of people with depressed parents or grandparents looked different from the brains of people with no depression in their family tree.

And there on the MRI scans, they found a startling difference. People at high risk of developing depression because of their family history had a dramatically thinner right cortex, on average 28 percent thinner than those who were not at risk.

Joining me now to talk more about it is my guest. Brad Peterson is director of child and adolescent psychiatry and director of MRI research at Columbia University Medical Center and the New York State Psychiatric Institution. He's here in our New York bureau. Thanks for coming in today, Dr. Peterson. Were you very surprised at what you saw?

Dr. BRAD PETERSON (Director of MRI Research, Columbia University Medical Center): Quite astounded, actually, in two respects. One was the magnitude of the effect at each point on the surface of the right hemisphere, but also the spatial extent.

I mean, it really extends from the back of the brain all the way to the front of the brain, on that side of the brain.

FLATOW: And why just that side? Do you have any idea?

Dr. PETERSON: Well, we have clues. You know, that finding led us to look into the literature that is decades old, as a matter of fact, that suggests that the right hemisphere of the brain is dominant for the processing of emotions.

It can be emotional stimuli that are coming in through your eyes from the environment, through the ears, that are communicated through language or gestures. And people who have lesions or problems on that side of the brain have difficulty in processing and remembering those kinds of stimuli.

And, in fact, in our data set, we found strong evidence that that was the case in people who have this right hemisphere thinning. And it was true not only in the group with the family history of depression. It was also true in the other group who didn't have a family history, so that those who have a thinner right hemisphere, in terms of their cortex, have the greatest difficulty in paying attention and remembering these kinds of stimuli, social and emotional stimuli.

So because the cortex is thinner in the high-risk group, they actually performed much worse and had greater problems in these areas, these cognitive areas.

FLATOW: 1-800-989-8255. Talking with Dr. Brad Peterson about this link between the cortex - the thinning of the right cortex in patients with depression versus those who did not have a familial, family relationship that might be predictive.

We have to take a break. If you'd like to send us a Twitter, you can send it @scifri. We're also taking emails at sciencefriday.com and also at Second Life. So we'll be right back, talking more with Brad Peterson, after this break. Stay with us.

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I'm Ira Flatow. This is SCIENCE FRIDAY from NPR News.

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FLATOW: You're listening to SCIENCE FRIDAY from NPR News. I'm Ira Flatow. We're talking with Brad Peterson, director of Child and Adolescent Psychiatry and director of MRI research at Columbia University Medical Center and the New York State Psychiatric Institute, talking about a dramatic thinning of the inner right cortex.

If it's so dramatic, how could you have missed it all these years?

Dr. PETERSON: A simple reason. I think no one ever looked for it. That's the main reason. People have focused, in their imaging studies of depression, on structures that have been known to be involved in the production and recall of emotions, structures like the amygdale and hippocampus - tiny structures deep in the brain, a couple of other structures near it.

No one has actually ever measured the cortex in people who are depressed or at risk for depression, and we simply look there.

FLATOW: Did you just have to have, in the correlation of depression, just a thinning of the right cortex, or did you have both the right and the left cortex? How did that work out?

Dr. PETERSON: Right. So you mentioned earlier that the right-hemisphere thinning was seen in the people who were offspring of depressed individuals. That's true.

You also indicated that it was present in depressed patients. That's true, although the most remarkable thing, in my opinion, is that the right-hemisphere thinning was seen even in people who - have themselves never been depressed or anxious.

Anxiety is an antecedent, often, of depression in familial depression. So we saw it even in people who've never themselves been depressed.

FLATOW: But might be in the future.

Dr. PETERSON: They may be in the future. In fact, we - and the other senior author of the paper, Dr. Myrna Weissman - are continuing to follow this cohort of people to understand how strong of predictors these are for the future development of depression.

Now in our data, we saw the right hemisphere thinning even in those who haven't been depressed. We also saw thinning in the other side of the brain, in the cortex of the left hemisphere, in those who have had depression in their lifetime.

And we interpret that as probably indicating that thinning of the right hemisphere places you at risk for developing depression, and you have these other cognitive problems, problems with inattention and processing of emotional stimuli.

You have that even if you've not been depressed. But if you also have thinning of the left hemisphere, that seems to tip you over from having a vulnerability to developing depression and from having these cognitive - subtle cognitive problems to actually manifesting overt symptoms of depression, anxiety and illness.

FLATOW: That would seem to imply, to a layperson like myself, that maybe the left hemisphere is taking over some of the burden in preventing those symptoms from being shown. Would that be a correct assumption?

Dr. PETERSON: I - we don't know if it's correct or not. We - I think the lay interpretation and understanding is consistent with what scientists also think.

No one exactly knows why we have two hemispheres of the brain, believe it or not, if that's obvious. We really don't.

(Soundbite of laughter)

FLATOW: We're that much in the dark about the brain?

Dr. PETERSON: We are in enormous darkness when it comes to the brain. The left hemisphere is dominant for certain things, like logic and language. And the right hemisphere is dominant for other things, such as the processing of emotions and connecting us in an interpersonal world.

So we probably have two sides of the brain, in part, to provide some redundancy. So if you have problems in one hemisphere, the other can pick up the slack, as it were. And if you have problems in the same part of both hemispheres, then you're in more trouble.

FLATOW: 1-800-989-8255. Melissa in Charlotte, North Carolina. Hi, welcome to SCIENCE FRIDAY.

MELISSA (Caller): Hi, thanks. I had a question about whether the -whether depression caused these brain changes in this study, because I had understood from other studies that I had heard about that depression causes these brain changes. But it sounds like in this study that brain changes were already there. Is that - can you answer that?

FLATOW: Which causes which? Does depression cause a brain change, or brain change cause the depression, I think is what you're asking, Melissa. Correct?

MELISSA: Yeah, Yeah. Correct.

Dr. PETERSON: Melissa, it's a superb question. In fact, that's one of the primary motives for undertaking this study with this particular cohort of individuals.

They were so valuable because they'd been followed by Dr. Weissman for more than 25 years. So they've been followed since, you know, birth through adolescence, young adulthood and even mid-adulthood and in their children, their offspring.

So one of the problems with a lot of brain imagining and biological studies, when you are studying already-affected people, people who are already ill, it's impossible to disentangle the causes of the illness from its manifestations, its consequences, its downstream effects, its -the compensatory responses, the things in the brain that try to take over to heal you, or even the effects of treatment such as medication.

So in this particular cohort, many of these offspring of depressed people had themselves never been depressed or anxious or ill in any way. And even in those people we find this marker, this really very prominent thinning of the right hemisphere.

MELISSA: Wow.

Dr. PETERSON: So even though they themselves haven't been ill, they do have these subtle cognitive problems, the more that they have this right-hemisphere thinning.

MELISSA: Okay, thank you.

FLATOW: Thanks. So you're just - you're basically connecting the dots without connecting the dots here.

Dr. PETERSON: Right, as much as we can do with human research, we are trying to connect the dots. You know, the ankle bone leads to the leg bone. It's, you know, family history. If you're born into a family with depressive illness, that seems to lead to cortical thinning. Cortical thinning seems to lead to these cognitive - subtle, cognitive problems and disconnection, if you will, from an emotional world. And that seems to place people at risk for developing depression. And if you have additional thinning in the left hemisphere, that tips you over into overt illness.

FLATOW: So when does this move from connect the dots to preventive medicine?

Dr. PETERSON: That is the goal of connecting the dots. That's why we try to understand causal pathways into illness so that we can develop rational therapeutics or preventive measures so that people who are really at risk for developing illness, we can intervene early and prevent them, hopefully, from ever becoming ill.

So we don't know when that'll happen with this kind of population, but I hope sooner rather than later, obviously. That's why we're doing the work.

But the - understanding these causal pathways provides important clues into how - what that therapy might look like. So if the pathway in is hemispheric thinning and these cognitive problems, then we can potentially intervene with behavioral therapies, psychological therapies like cognitive training, cognitive exercise, and medication that can help attention in people who have this family history in cortical thinning.

So it may be that there are other kinds of depression out there that aren't like this, that aren't familially based, you know, that don't run in families or that don't have this hemispheric thinning, then they'd probably respond to a different kind of treatment. But we hope that this may lead to targeted therapies for very specific individuals who can benefit from it. But we think that a lot of people out there have familial depression.

FLATOW: Is it possible - you know, a lot of times, scientists will see an illness, and then they want to recreate that illness as much as they can in laboratory animals so they can study it. Can you do that? Can you find mice or whatever who have this kind of illness, the cortical thinning, and then find possibly a genetic cause for these sorts of things?

Dr. PETERSON: That's a great question, and we've been thinking of exactly that, speaking with our basic scientist colleagues at Columbia and elsewhere.

And there are lots of potential ways of doing that. You can potentially lesion the right hemisphere, see if we can create a model and then find ways to intervene and improve it.

It may be that as we find some of the genetic causes for depression, that we may be able to - well, if we do find those genetic causes, we can create animals that have that genetic problem, and then we can look at what's going on in that right hemisphere at the level of nerve cells and their connection.

So we can do that. We can also understand some of the environmental effects that can also produce depression. So depression isn't only caused by genes. It's also environment, especially early environment, and in this particular sample of people in our study, we're not able to disentangle a genetic effect that's transmitted through the family versus an environmental effect that also is transmitted through family.

So a young child growing up in a household with depressed parents, we've known a long time from developmental psychology that that affects the offspring. And that, in fact, could be manifest in terms of brain structure.

So whether it's genetic or environmental, whatever the cause, ultimately, it's being hard-wired into the brain very early because…

FLATOW: How early do you see it showing up, the thinning?

Dr. PETERSON: Well, the youngest of our participants was age six.

FLATOW: Age six.

Dr. PETERSON: And the oldest is 54. And we found it both in the children and in the adults. And if anything, the finding was a bit more prominent in the children.

And that's clearly before they've ever become ill. So that's extraordinary, really, and it suggests that we really might be able to intervene early to prevent depression.

FLATOW: Does this encompass all flavors of depression? I'm not sure I'm even describing it correctly, you know? I mean, the thinness could account for every kind of depression that we're seeing.

Dr. PETERSON: I'm almost certain that it will not. Depression is highly - has multiple different causes. There are clearly different kinds of depression. Early onset depression, the kind that we're studying, familial depression tends to be earlier onset, more recurrent and more severe. Late-life depression tends to have other causes rather than familial transmission. So, almost certainly, this doesn't cover all forms of depression. But I should note that in our data that even in the group, half of the subjects who were at low-family risk, some did have depression. So they're at low risk, they weren't at zero risk.

FLATOW: Right.

Dr. PETERSON: Some have had depression in their lifetimes. And those who had had depression still had this same pattern of thinning. So, it suggest that - we're certain that those at familial risk had this thinning, and it's also possible that even those without a family, strong family history, also had it. So this may be a more general marker…

FLATOW: Right.

Dr. PETERSON: …for people at risk for depression. But that's softer because it's a smaller number of subjects.

FLATOW: Yeah.

Sam(ph) in Oakland, California. Hi. Welcome to SCIENCE FRIDAY.

SAM (Caller): Hi. This is really fascinating to me. I have two cousins that have been diagnosed with depression, and my sister is diagnosed with bipolar.

And I was wondering about these brain scans, like, if that would help in the diagnosis process, because I'm not totally convinced that they are getting - my cousins got the best care compared to what my sister got, more comprehensive diagnosis. And I know you said that you can - this may be only explained as certain amount of depression, but I'm just interested in how that might help diagnosis. As well as, you have said cognitive problems that might be a precursor to depression. Could you elaborate on that?

Dr. PETERSON: Two big questions.

FLATOW: Yeah. Take - we're running out of time, so do the best you can.

Dr. PETERSON: I'll address the issue of diagnosis. So, currently, the measures that we were able to employ are really sophisticated and they're not generally available out in the community. And five years ago, I would have been highly, highly skeptical that anything with brain imaging could actually diagnose disorders.

But increasingly over the last five years, in our data sets and other data sets, we've seen very distinct patterns of abnormality in brain tissue that seems very specific to certain kinds of disorder. So, it's not at any particular point of the brain that you can say, oh, you know, there's a problem at this single point that means it's this disorder rather than another one.

But if you look at the brain as a whole and this pattern of thinning or this - or pattern of abnormality, I think it is much more likely to be potentially diagnostic in the future even though it's not there yet. So, other disorders have cortical thinning.

FLATOW: Yeah.

Dr. PETERSON: Schizophrenia, Alzheimer's, very severe illnesses and less severe illness, but they have distinct patterns of thinning. And this is a very, very distinct one that hasn't been described in the other illnesses yet.

FLATOW: Dr. Peterson, I want to thank you for taking time to be with us today. Fascinating. Good luck to you.

Dr. PETERSON: Thank you.

FLATOW: Brad Peterson is director of Child & Adolescent Psychiatry and director of MRI Research at Columbia University Medical Center and the New York Psychiatric Institute.

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