Puberty and Brain Development – NIMH study

[music]>>ASHLEY HUCHT: Hi. I’m Ashley Hucht with
the Behavioral Endocrinology Branch at the National Institute of Mental Health. A team
of investigators at the NIMH are examining how puberty affects brain development during
adolescence. The NIMH wants to find out how the brains of children develop at a time when
hormones and growth patterns change. This study is a collaboration between Dr. Peter
Schmidt, Chief of the NIMH Behavioral Endocrinology Branch, and Dr. Karen Berman, Chief of the
Section on Integrative Neuroimaging and the Clinical Brain Disorders Branch. Also on the
team, we have Dr. Pedro Martinez a child psychiatrist. And doctors Shau-Ming Wei and Katherine Reding,
neuroscience research fellows. I’m joined by Dr. Peter Schmidt, who specializes in the
role of hormones on mood and behavior. So, Dr. Schmidt, let me start with you. What is
the purpose of this study and what does it involve?>>PETER SCHMIDT: The question we’re trying
to answer in this study is what would be the role of puberty? In particular, the activation
of the hypothalamic–pituitary–gonadal axis which creates the, uh, adult functioning
testes in boys and a cyclic ovarian cycle in girls. Uh, what is the effect on that,
those events on brain development? So in order to this, was several things that we had to
be very careful about. The first is that we need to study boys and girls who are clearly
prepuberty. Meaning, that they haven’t started any indication of puberty at this point in
their life. After that, we then follow them on a regular basis over every 8 to 10 months
longitudinally to be able to identify what changes may be occurring as a function of
puberty starting. So, uh, the second issue is that each of these clinic visits, we perform
brain imaging studies to measure changes in specific parts of the brain. We also, at each
clinic visit, measure hormone levels by taking blood samples. We also collect the urine samples
and saliva samples to measure some of the stress hormones. And finally, we ask questions
about symptoms. Whether it’s related to their sleep. Whether it’s related to anxiety symptoms
or, uh, a variety of other measures.>>ASHLEY HUCHT: You’ve taken the lead to
coordinate what I suspect is a major logistical undertaking working with the children and
their families.>>PEDRO MARTINEZ: 00:02:40.915 The children
and their parents are invited to come back to the outpatient for clinic at the National
Institutes of Health every 8 to 10 months. Um, we do this until the re– the children
reach the age of 17, which is a big commitment for everyone to participate in. But the amount
of time and commitment that these families, uh, spent on this project has, has been very
important and very rewarding.>>ASHLEY HUCHT: What are the tests you use
in the MRI to measure brain development and what does this tell you?>>SHAU-MING WEI: 00:03:09.416 So the children
come in once every 8 to 10 months and they spend about half a day in the clinic. Um,
but we also use several neuroimaging tools to understand, uh, to gather important information.
So for example, we use risk x-ray to understand brone– bone growth over time. We also use
MRIs to look at brain development, to look at changes in fat distribution in the abdominal
area. And also the growth of testes and ovaries across time. We know from studies in animals
that several important brain circuits go through dramatic changes during the pubertal transition.
So we designed some games that children can play when they come visit us, uh, so we can
understand the changes in these brain circuits. So for example, we have a game that can help
us understand, um, emotional regulation. Uh, we can al– We also have a game that targets,
uh, um, impulse control. Uh, we also have one that understand how memory changes. Me–
And also, uh, a game that look at, um, changes in reward processing.>>ASHLEY HUCHT: Dr. Reding, how is puberty
different from adolescence?>>KATHERINE REDING: Well, adolescence is
loosely defined as the time period between childhood and adulthood. Um, it involves different
emotional, psychological, and physical changes. Puberty, however, is a specific biological
process that is embedded in adolescence.>>ASHLEY HUCHT: Why are you starting with
boys and girls that are eight years old?>>KATHERINE REDING: So one of the critical
elements of the study is recruiting a prepubertal cohort. So by bringing children in at eight
to nine years of age, we are more likely to recruit kids that are prepubertal. In addition,
by bringing in children that are eight years old as opposed to say, six or seven years
old, we’re also getting slightly more mature children. Which for us will mean that they
might be better at doing some of the neuroimaging tasks, which are very difficult. Oftentimes,
you have to stay still for long periods of times and older children are a little bit
better at staying still than younger children.>>ASHLEY HUCHT: I understand that the children
have an appointment with you every nine months. Why is important to complete a physical exam
and access pubertal development at each visit?>>PEDRO MARTINEZ: T-the physical exam is
a tool that physicians have been using in medicine since– for centuries and is one
of the first tools that we use in order to assess health and abnormalities as– in, in
the body. In this particular study, we’re interested in assessing the changes that happen
in the transition into puberty as the hormones start, you know, uh, kicking in and signaling
the transition into puberty. Um, the reason we measure, uh, reproductive organs during
these visits is because that is usually the first sign of change and the first sign of
puberty in the transition.>>ASHLEY HUCHT: I understand that you interview
children and their parents at each visit and they complete multiple questionnaires. What
does this information tell you and why is it so important?>>PEDRO MARTINEZ: It important for us to
record and to measure what kinds of changes are happening in behavior, um, and mood across
the transition into puberty.>>ASHLEY HUCHT: Dr. Schmidt, if you’re exploring
how puberty is related to brain changes, is there anything that you’re trying to rule
out to ensure that it is puberty and not something else?>>PETER SCHMIDT: That’s a very important
question. Um, in addition to the activation of the testes in boys or the ovaries in girls
that we would call puberty, there are several other important physiologic events that occur
at d– at this time in adolescence. Specifically, adrenarche, which is when an element of the–
or a section of the adrenal cortex, which is the gland that produces stress hormones,
uh, suddenly becomes active and starts producing hormones that have a testosterone-like effect
and obviously, could impact on brain development. Second physiologic system that develops is
the growth hormone system and related to the growth spurt. Both boys and girls go through
a growth spurt where they, um, have an acceleration of their normal grown– growth velocity. And
this is under the control of several hormones. All of which may impact our brain development.
So it’s important at the end of the study that in each child, we have a measure of when
these milestones occur, and then we can look to see what their impact may be on the neuroimaging
measures that we’re– that we’re obtaining in these children.>>PETER SCHMIDT: Second, uh, important element
is that we need to recruit a group of healthy adults who are young adults who presumably
are not undergoing any of the major changes that are happening, uh, hormonally in the
children. And we scan them at a similar period of time in order to get a measure of what
would be the effects of just time as opposed to puberty on these same brain measures that
we’re collecting. Finally, it’s important that we recruit both boys and girls. And in
fact, at this point, we’re looking for more girls to recruit who are in the eight-year-old
group in order to be able to identify at the end whether there are sex differences and
whether these sex differences in brain development occur at different times or are under control
of different physiologic systems in boys compared to girls.>>ASHLEY HUCHT: Why is this information so
important to NIMH?>>SHAU-MING WEI: Adolescence is a time where
we see dramatic increases in neuropsychiatric illnesses. And the emergence of sex differences in several
of these conditions including anxiety and depression. Uh, we also know from studies
in animals that several important brain circuits go through dramatic changes during this critical
period. And finally, by understanding what normal development looks like in healthy children,
it’ll help us understand why or how these sex hormones affect children at risk at acquiring
these diseases.>>ASHLEY HUCHT: Will the children’s names
be published in papers?>>SHAU-MING WEI: No, they will not. The children
will remain anonymous in these studies.>>ASHLEY HUCHT: Is compensation provided?>>SHAU-MING WEI: Yes. Compensation is provided
every time they come visit us. [music]

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