NIMH Facebook Live: How Does Puberty Affect Brain Development?
>> PETER SCHMIDT: Good afternoon. The NIMH is hosting this event. Uh, in recognition of National Children's Mental Health Awareness Day. Um, my name is Peter Schmidt. I am the Chief of the Behavioral Endocrinology Branch within the NIMH. And along with my collaborator Karen Berman, we have been conducting a study looking at the effects of puberty on, uh, typically developing boys and girls. Now, unfortunately, Dr. Berman is not able to join us today but we are joined by two of our lead investigators, Dr. Shau-Ming Wei, who's a research fellow within our group, and Dr. Katherine Reding, who is a post-doctoral fellow in our group. Now, during the first part of this session, we'll be discussing some basic aspects of puberty, what we know about the effects of puberty on brain, and why-- or what do we hope will be, uh, questions will be answered by this study. Now, certainly, in the second part, we will be open to questions, um, and so, please, if you have any questions, you can send them in during-- at any point during this, uh, this event. Uh, one program note is that we are unable to provide any specific medical advice or referrals but that you are encouraged, if you have questions about diagnosis, treatment, or any other personal questions, to seek out a qualified health care professionals. Uh, if you need help doing that, there will a website, an NIMH website called, uh, Find Help, I believe, that will, uh, be sent out and there, there is information on that site. So, um, just to begin with then, um, let me ask Dr. Reding a question about how we distinguish between adolescents and puberty.
>> KATHERINE REDING: Okay. Well, thank you. It's so good to be here. Um, so adolescence is a time of transition from childhood to adulthood. This includes everything that happens at that time period. Uh, that means changes, uh, in the body, changes in emotion, and changes in, uh, psychology. It even includes changes in social roles and responsibilities. Uh, but puberty is actually a specific biological process that is embedded within adolescence. Um, it's, it's the combination of all the biological processes that are needed to produce adult reproductive function. So in other words, age is-- uh, sorry. Adolescence is really just, um, at look at age while puberty is more a look at the cascade of hormonal events that are occurring at this time.
>> PETER SCHMIDT:[inaudible] and while you're, uh, reviewing this, could you tell us what we know currently about the relationship or the effects of puberty on, uh, brain development in normal boys and girls?
>> KATHERINE REDING: Mm-hmm. I'd love to. So we don't know exactly how puberty affects brain development. Uh, but we do have a few clues. So one of our first clues comes from animal research. And here what we see is that, um, the connections between brain cells or neurons, seem to go through a process called pruning during puberty. Um, what this means is that the connections between the neurons, um, are altered, they're changed. So some might disappear altogether while others become stronger. Um, our other clue comes from human brain imaging work in adolescents. And we see here is that as children age, different, uh, parts of their brains, uh, specifically the ones that control behavior, they seem to be maturing at a slower rate than the part of the brain that drives behavior. So you can think of this as brakes in a car. So what's happening in adolescence is that these brakes on behavior are maturing. So putting the-- putting these things together, we think there is significant pruning happening in these control regions throughout puberty. Um, and what we're trying to figure out here in the study is when those changes might happen and what pubertal events might be causing those changes.
>> PETER SCHMIDT: One, one follow-up question on that is that, that Dr. Wei will talk a little bit later about some sex differences, uh, that emerge around the time of puberty in a number of conditions. Um, are there-- is there any information about sex differences related to brain development at this time?
>> KATHERINE REDING: Mm-hmm.
>> PETER SCHMIDT: Because given the sex differences in the way puberty and the hormones involved in puberty, you might anticipate some of this.
>> KATHERINE REDING: Yeah. So for the adolescent, uh, human neuroimaging work - excuse me - uh, it really looks like there is a slight difference in timing of this pruning that might be happening in the brain where girls might go through this pruning earlier than boys. However, we don't really know if this is because of, uh, puberty or adolescents or age. Uh, girls also tend to go through puberty earlier than boys. So it might be linked together. So, again, there are clues out there in the adolescent research that there are sex differences but we really don't fully understand, uh, how puberty and sex differences in puberty might affect brain development.
>> PETER SCHMIDT: Great. Thank you. So as Dr. Reding described it or implied that puberty is a very complicated physiologic phenomenon that-- and there's a tremendous amount of individual variations. So in order to conduct this study, one of the most important features is that we make sure that every child, at least th-those eight-year-olds, is in the pre-pubertal state. So they had to know-- we, we go to great lengths to make sure that there's no evidence that they have started puberty. And we do this with a, a number of measures. Um, but essentially, we then follow them over a period of approximately 10 years seeing every boy and girl 8 to 10-- a-at 8- to 10-month intervals. And we perform a number of, uh, brain scans looking at measures of many of the things that, that Dr. Reding talked about. We also look at a number of bi-- or take a number of biological samples including blood tests that will tell us about exactly what is happening in the pubertal process in these boys and girls. We also measure a phenomena that, uh, Dr. Wei will talk about later related to growth and metabolism. Now, what we hope to get then, is on an individual basis, a map that will tell us about, uh, what happened to this boy or girl over this 10 year period. Now, if-- just as an aside, although I [inaudible] receiving no product placement, uh, uh, activity here. But if any one of our viewers would like to participate in the study, the number to call is 301-496-9576. And you may hear me repeat this 1,000 times over this, uh, this session. So Dr. Wei [crosstalk].
>> SHAU-MING WEI: [inaudible] yeah. So I would also like to add that at the end of this study, our goal is to compose an individual navigational map of each child of these key physiologic events that occur during this important transitional period that is puberty, um, that also include, for example, growth spurts or, in girls, the onset of first menstrual bleeding. And what we can do is take these events, this, uh, physiologic milestones and look at how they change together, uh, with brain during development across puberty.
>> PETER SCHMIDT: Yes. So in other words, we'll be able to identify within each individual boy and girl, when this event occurred. For example, the growth spurt. And then look at the brain--
>> SHAU-MING WEI: Imaging.
>> PETER SCHMIDT: --imaging before and after that. Because what's most important is that given all these things happening, the-- at the end of the study, we want to be able to evaluate what are the effects of this specific activation of the gonadal axis, which is called-- you know, part of which we assume is part of puberty. And distinguish that from, say, the growth spurt and the hormones that are produced then which could also impact on brain development as well as a variety of other, uh, physiologic events. So Dr. Wei, then, um, maybe just to continue, can you tell us why this is important? Why are we doing this study?
>> SHAU-MING WEI: So adolescence is a time where we see dramatic increase in a range of neuropsychiatric illnesses and the emergence of sex differences in a number of these conditions including schizophrenia, anxiety, and depression. So by studying how puberty related physiologic milestones and brain changes in typically developing children, we can then understand how these effects are different in children that are at risk of developing these, um, neuropsychiatric conditions. And so these data then will help other investigators to understand, uh, development.
>> PETER SCHMIDT: So we'll not only be able to understand precisely, we hope, what happens, uh, what are the effects of puberty and the onset of, of sex hormone secretion by the gonadal organs, um, in terms of brain development. But in collaboration and with sharing with other investigators, we'll be able to see how, for example, uh, the effects of early life trauma may impact on brain development at the time of puberty or children, uh, boys and girls, who say there's this large, uh, as Dr. Wei mentioned, a large increase in, uh, conditions like depression and anxiety that we start seeing in girls really after the first, uh, menstrual bleeding. Whereas prior to that, there seems to be an equal different-- equal prevalence of depression and anxiety in both boys and girls. So these are the, uh-- those are the long-term effects. Once we can identify what are the important factors of puberty, then that can be shared with other people and they can start pursuing those studies themselves. So I think, um, the next phase is to, uh, uh, address some of your questions. So please, uh, again, um, send in the questions. We'll try to get to all of them by the end of the session. If not, there may be some follow-up. And I also remind you that we are not able to provide, um, specific medical advice or referrals but that you're encouraged to see your, your health care provider. So, um, let me ans-- address one question now. Um, one of the audience is asking, "Why are you starting with eight-year-olds? When does puty-- puberty normally begin?" Maybe Dr. Reding can, uh--
>> KATHERINE REDING: Sure.
>> PETER SCHMIDT: --address that one.
>> KATHERINE REDING: Sure. So we're starting with eight-year-olds firstly because we want to capture children before they start puberty. Um, but also we want to try to get children that are older and that can handle the, uh, neural imaging protocols more easily. It's difficult to stay still in a neural imaging scanner, uh, so older children tend to stay still, uh, more easily. So by recruiting children at eight, we're getting them as close as we can to, uh, the start of puberty while still being before puberty and also trying to capture children that can do the protocol.
>> PETER SCHMIDT: Okay. Next question. Does puberty affect if-- affect the effectiveness of medications? And that's a good question. It's, it's a tough one. Um, certainly, we know that age-- so some antihistamines, um, that are taken, they're metabolized differently in younger children compared to older adults. Um, sometimes faster, sometimes slower. And, and this is actually one, uh, frequent event that comes up in our study because during, uh, you know, s-- uh, allergy season in Washington which is about 10 months out of the 12, uh, you know, children often take, uh, allergy medications and then we have to kind of-- when we hear about that at the last minute, we have to delay scheduling. So there certainly is an age-related effect. As to the specific effects of puberty, I, I think going back to, uh, Dr. Reding's question, no one knows. Um, certainly, sex hormones may impact the metabolism of some medications. Um, we know that from women who have been on the birth control pill or oral contraceptives that there may be interactions or women, um, taking medications that, say, block estrogen, may impact the metabolism of certain antidepressants so-- uh, and alter their effectiveness. So it's quite likely and it's plausible but we do not know specifics at this point.
>> SHAU-MING WEI: And actually-- uh, a follow-up question though. I don't think there are any evidence that-- or I don't think that currently there are any medications that have different doses in boys and girls.
>> PETER SCHMIDT: No. You're correct. Yeah.
>> SHAU-MING WEI: So we don't really know.
>> PETER SCHMIDT: Yeah. That's a good point. Yeah. Okay. Will nutrition be a factor in this study? I would hand that over to Dr. Reding yet again.
>> KATHERINE REDING: Excellent. So although we're not taking specific measures of what kids are eating every day, uh, we are trying to take nutrition into account. And we do this in two different ways. Uh, so first we're going to be measuring the BMI of all the participants in our study. Um, so for this we're, we're, we're measuring BMI because we actually want to control for a specific range of BMI values. So we're only recruiting children to-- into the study that are between the 15th and 85th percentile of BMI. Uh, and this mostly because BMIs that fall on the higher or lower end seem to be, in some way, possibly related to either an earlier or a later onset of pubertal development. The second way that we're looking at nutrition in the study is by examining skeletal bone growth or bone age. Uh, we do that by taking an x-ray of the wrist, uh, and examining the fusion of the growth p-- uh, of the growth plate. So bone age, uh, tends to reflect mostly, uh, estradiol's action in the body but it also a cumulative measure of exposure to nutritional states, uh, any kind of disease factors, and general health. Uh, and for this, we're recruiting children that have a-- on average, they fall between the 90th percentile-- uh, oh, sorry. The 90, 90% confidence interval, uh, to age and sex match controls.
>> PETER SCHMIDT: Okay. The next question is a, uh, uh, more of a personal question. Is how do we contact you? We are concerned about our son's mental health. Uh, certainly, I would be happy to speak with you kind of offline. You can reach me either through the number on your screen which is our general recruitment number, 301-496-9576, or you can contact me through the organizers and I'll, I'll be happy to, uh, call you back. Okay. Um, we are waiting for a question.
>> SHAU-MING WEI: [inaudible]. Yes. There are-- someone [crosstalk]--
>> PETER SCHMIDT: Oh, [inaudible] somebody's asking about other clinical trials.
>> SHAU-MING WEI: Right.
>> PETER SCHMIDT: Changed font on [inaudible].
>> SHAU-MING WEI: So, um, there are many clinical trials that are currently happening in the National Institutes of Mental Health. And the way of searching if you're interested as a healthy volunteer or, um, or children, um, or patients of any, uh, condition, you can go on clinicaltrials.gov and if you type in the keywords such as healthy volunteers, um, or disease of interest then, um, there should be a list of available protocols for you to then choose from. And we really appreciate any interest in participating in clinical trials because it helps us really further understand how, um, these conditions, um, really change.
>> PETER SCHMIDT: Great. Okay. So next question. Can we connect these findings with learning? Um, this, uh, person's 11-year-old son is not that interested in school. Is there hope that maybe he'll be able to put down the video games. So, um, answer to the first part of the question is yes, we hope that, um, those brain regions that we're studying will be a-able to answer a question related to certain types of learning. Uh, and I can-- uh, either my associates could fully address that who are more involved in the brain imaging. But, yes. And we're also monitoring, uh, some, uh, cognitive test performance throughout the study. Um, before I pass that along, as a parent, I think there's always hope that our children will stop playing video games. Now, as a old parent, I've recently taken up playing video games and have children that played video games and they're earning a lot more money than I am right now. So, you know, have hope and have faith in the gene pool. Um, uh, maybe-- a-and so, you know, I think a lot of children go through ups and downs about their interest in academics and, uh, you just hope, I think, that you find-- that they will find something that they love and they want to commit to for, you know, a good part of their life. And, uh, if you have concerns, however, it's time to either talk to your, your, your son's teachers or your, your health care provider. Maybe around the learning--
>> SHAU-MING WEI: And-- well, there's learning and also, at least for our particular study, we, uh, can't really take, um, screen time into consideration because we have, um, different questions that we're answering in this-- our particular study. And that is to really understand how the different hormone profile, uh, changes with brain across puberty. However, there are, um, other studies of development that are really interested at looking at screen time and that includes the ABCD study which is the adolescent brain cognitive development study. And, um, they are-- I kn-- I know they're recruiting participants. So if you're interested, please, go on their website. Um, and I think Dr. Reding-- do you have anything to add to the learning?
>> PETER SCHMIDT: Um, just-- may I in-intervene for just a second? [crosstalk]--
>> KATHERINE REDING:Yes. Please. [inaudible] yeah.
>> SHAU-MING WEI: Sorry.
>> PETER SCHMIDT: --intercepted the pass. Um, there have been some studies suggesting kind of a negative effect of screen time in adolescent development.
>> SHAU-MING WEI: [inaudible].
>> PETER SCHMIDT: But one recent study that came out of, uh, University of Oxford suggested-- and, and carefully monitored screen time in these children and found really no evidence of any impact of long screen time on the child's development and school performance. So I think it still remains controversial, um, but, uh, we'll wait and see. So--
>> KATHERINE REDING: Yeah.
>> PETER SCHMIDT: An answer in evolution.
>> KATHERINE REDING: Mm-hmm.
>> PETER SCHMIDT: So you were going to pursue the question [crosstalk].
>> KATHERINE REDING: Oh, do you want me to field the-- okay. Sorry. I, I think the question also might be tapping into, um, kind of what different networks are changing in the brain at this time. So if we're thinking about learning, we're thinking about attention and circuits that are associated with attentional behavior and intentional processes. Um, video games might be linked to part of the reward processing centers in the brain, uh, and reward-seeking behavior. Um, so I think what the study will be able to tell us, not specifically for your son's behavior but kind of in general for this adolescent pubertal change, is that will we see kind of a change in balance between the rewards seeking networks and those cognitive control networks. And that also goes back to kind of what I mentioned earlier in the beginning, um, of the session is that we actually think those cognitive control regions are developing more slowly. Um, so it's a great question and, hopefully, we'll be able to offer some insight into how puberty might specifically impact these networks.
>> PETER SCHMIDT: Okay. Another program note. Uh, it's 2:20 and we're nearly through our time today. So for those of you who are just joining us, we're here today from the National Institute of Mental Health who-- in recognition of, um, Childhood Mental Health Awareness Day. Uh, we're here to answer your questions about puberty and brain development. And I think we have time for a couple more questions. Um, so how does anxiety affect puberty and vice versa? Well, just to start, I think, uh, Dr. Wei had mentioned that it's the current studies that have looked at community-- many children in the community have identified that, at least th-the emergence of sex differences and anxiety where, uh, women will have a two to three-fold increase in the, uh, uh, prevalence of anxiety conditions compared with men. And that these-- the sex difference and prevalence doesn't seem to appear prior to, uh, the onset of the menstrual bleeding or what's called menarche in girls. Uh, there have been studies that have looked at earlier or later puberty. Uh, either called delayed puberty when it's later or precocious puberty, uh, in-- when it's-- when puberty is much earlier, say, prior to eight-years-old. And there does appear to be a statistically significant clustering of anxiety conditions when puberty is early. Again, mainly in girls. But, um, these studies have been small samples and certainly, the causes of early or late puberty may overlap with, uh, other medical conditions that are also associated with anxiety or depressive symptoms. So that na-- the nature of that relationship, there are studies trying to look at this but, again, it's unclear and, uh, certainly there are many children with early puberty or late puberty that have no, um, behavioral abnormalities whatsoever. So no anxiety. Okay. Um, any comments about [inaudible]?
>> SHAU-MING WEI: No [crosstalk].
>> KATHERINE REDING: That's good. [crosstalk].
>> PETER SCHMIDT: --[inaudible] that one was, you know, well answered. So--
>> SHAU-MING WEI: [inaudible].
>> KATHERINE REDING: But actually, the-- I think the second question--
>> PETER SCHMIDT: Okay.
>> KATHERINE REDING:--is a good follow-up.
>> PETER SCHMIDT: [inaudible] in your study, what other aspects of mental health will you measure or expect to see?Dr. Wei
>> SHAU-MING WEI: Okay. So this-- again, this study, we really focus on typically developing children. We really want to understand how physiologic milestones in puberty and, and in concurrence with brain changes, uh, during this time, uh, can be measured because really there has-- there have been no studies before the current one trying to look at the changes between these events. Um, so we-- in our study, we really try to, uh, do questionnaires and have, um, clinical interviews to make sure that these, um, the children in our current study are, uh, typically developing, without any neuropsychiatric illnesses. However, there are instances when, um, these, um, illnesses do develop, um, during the course of the children in the study. And what we usually do is refer them to other studies in the NIMH to further follow these children.
>> PETER SCHMIDT: Yes. And certainly, one other, um, um, phenomena that we're trying to study is in some of the girls that we've noticed that the onset of menarche, they've, um, begun to experience some changes in, uh, sadness or irritability. And so we're, we're only able to follow these girls up to age 18 but we're hoping that, related to some of the other studies in the behavioral endocrinology branch, that we may be able to start tracking some of the early onsets of conditions like premenstrual dysphoric disorder or, possibly, the more general conditions related to anxiety or, or sadness and depression. So, um, the question, it's interesting. I thought each of us could answer this as I'm sure there may be individual differences in how surprised we were. So the question is, what's the most surprising learning relative to this study that you've had so far? So, you know, myself, I've been surprised at how girls don't seem to want to tell us when they are having their menstrual period and that we've gone to great lengths and that-- and that are still struggling with that because what we try to do in each of the girls is schedule-- in order to get a, a consistent hormonal state whenever we're doing these studies because, obviously, we're studying the potential effects of hormones on brain. So we want to make sure that that's standardized.
>> KATHERINE REDING: Mm-hmm.
>> PETER SCHMIDT: And we need to schedule the girls during a specific part of their cycle. And unfortunately, they tell Dr. Wei maybe five days after their period has start and that's only after calling them every day. Not all of them but some, and you'll know who you are out there. Um, we, uh, we end up, uh, you know, being jammed to try to schedule, uh, our other procedures in that time. So that's been a little surprising to me. But we're problem-solving on that and we have some phone apps that we're developing. You ready?
>> KATHERINE REDING: Um, I'd like to take the moment to kind of talk about some of the preliminary findings from our study.
>> PETER SCHMIDT: Okay.
>> KATHERINE REDING: Um, so, um, there's one type of neuroimaging protocol we use called resting state MI. And in this type of neuroimaging protocol, the kids are laying in the MRI scanner and are asked to just think about anything they want to think about. They're not looking at anything. They're not asleep so their eyes have to stay open. And it's a really difficult scan for kids to do. Um, but the cool thing about the scan is it lets us really probe the brain and probe all the networks that are active in the brain at once. So one of the first things that we found is that in our pre-pubertal sample, just looking at the first visit of, uh, approximately 50 children, we actually were able to see sex differences in these brain networks before any gonadal hormones were online. Uh, and to me, that was surprising because my hypothesis was that the onset of these gonadal hormones would cause the sex differences. But here we're seeing those sex differences before those changes start happening. So thought here is that those changes are maybe resultant of earlier exposures to estrogens. So there is a, uh, time period, uh, during fetal development and right after birth that children actually go through a mini-puberty. So they're exposed to smaller-- well, it's still a large amounts of, uh, estradiol but a short, brief period of time, uh, before the hormonal axis, uh, the reproductive axis kind of shuts down or gets the brakes put on it. So it could be related to that. It could be related to social factors. It could be re-- uh, related to other environmental exposures. But I was really surprised and I think it's a really cool finding. And as we build up our sample size, we'll be able to really say if this-- if, if this finding holds, uh, and, and might be something to add to the literature.
>> PETER SCHMIDT: Great. Dr. Wei.
>> SHAU-MING WEI: So it's interesting that, uh, Dr. Reding, uh, thought that was surprising because, um, I-- uh, when looking at some of the other sort of games or tasks that these children are doing including one task that looks at how their reward circuitry develops. We actually didn't find any sex differences, uh, in the reward circuitry prior to the onset of puberty. And I thought that was quite surprising because I think, at least behaviorally, there are some evidence that they do already experience, um, differences in reward processing. And, again, since, uh, there are many psychiatric illnesses that have sex differences that emerge around puberty, so maybe we will then be able to measure some of these when puberty really hits. But I, I thought that was quite interesting that we saw sex differences in some of our paradigms but all of our paradigms prior to the onset of puberty.
>> PETER SCHMIDT: So that-- your comments actually lead to our last question which, unfortunately, we need to end. Um, how many children are you-- do we wish to, uh, recruit for the study. And so, uh, we're looking for a group of approximately 50 boys and 50 girls who started this study at 8 and finished it at age 17. So that's about 10 to 12 visits per child--
>> PETER SCHMIDT: Uh, so it's, like, over 1,400 visits. Obviously, that should be enough to address-- especially with the, the carefulness with which we're describing, um, our pre-pubertal sample as well as some of the, uh, involved measures of, say, reward functioning or other brain circuitry, uh, that, uh, we heard about earlier today. So-- okay. So that's all the time we have today. Um, thank you to everyone who tuned in. And, uh, this was the unscripted part. So-- and somebody keeps moving it. Um, so those who submitted questions, we also thank you. Uh, if we didn't get to your question, we will try to get back to you with-- uh, by email. Uh, the video will be available on the NIMH Facebook page if you want to watch again or share with your friends. Thank you very much for tuning in.
>> SHAU-MING WEI: Thank you.
>> KATHERINE REDING: Thank you.