Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT01434368 |
Other study ID # |
110251 |
Secondary ID |
11-M-0251 |
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
November 23, 2011 |
Study information
Verified date |
February 26, 2024 |
Source |
National Institutes of Health Clinical Center (CC) |
Contact |
Peter J Schmidt, M.D. |
Phone |
(301) 496-6120 |
Email |
peterschmidt[@]mail.nih.gov |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Despite the clear importance of adolescence in the emergence of a number of disease states
and processes, there is surprisingly little known about how the endocrine and metabolic
events accompanying puberty in humans impact normal developmental neurobiology. Epidemiologic
studies have identified sexual dimorphisms in the prevalence of several neuropsychiatric
disorders, including depression, schizophrenia, and substance abuse. Many of these sex
differences emerge during or shortly after puberty and are maintained until the 5th-6th
decade of life. For example, the two-fold greater risk of unipolar depression in women
compared with men does not appear until adolescence, and prior to puberty girls are not at
increased risk relative to boys. Puberty is a structured, transitional process that can be
influenced by both nutritional factors and environmental stressors; nonetheless, the
variability in the timing and duration of puberty is largely determined by oligogenic
inheritance. Basic neuroscience research has demonstrated that hormonal events accompanying
puberty impact on many of the physiologic systems involved in the regulation of brain
function (e.g., the appearance of new neurons in a brain-region specific pattern, neuronal
remodeling, and the pruning of cortical connectivity). Additionally, not only does stress
during puberty increase the risk of disturbances in affective adaptation during adulthood,
but the events accompanying puberty modify stress responsivity (e.g., alterations in the
duration and peak response of hypothalamic-pituitary-adrenal [HPA] axis hormones to
stressors). Moreover, animal work has demonstrated that neural connectivity differs in a
brain regional specific manner according to the stage of puberty (i.e., early versus late).
In humans, puberty also occurs in stages, and although the endocrinology of puberty,
surprisingly, has not been fully characterized with longitudinal data, studies have
documented that the physical changes measured by Tanner stages I to V are accompanied by
progressive increases in the secretions of both gonadal and adrenal steroids. Nonetheless,
there remains considerable variability in the timing and duration of this otherwise highly
structured reproductive transition.
We propose to perform a longitudinal, naturalistic study examining changes in brain structure
and function, behavior, and stress responsivity in boys and girls across the pubertal
transition. Because the pubertal transition is defined by a complex series of physiologic
events that emerge sequentially over several years and involve changes in multiple endocrine
and growth systems, and because there is also considerable variability in the timing of these
events reflecting the influence of both genetic and environmental factors, puberty cannot by
delineated by age of the participants as has been done in most imaging and other
neurobiological studies of adolescence. The present study will formally bridge this gap by
defining pubertal events per se in participants.
Participants will include healthy boys and girls whose pubertal status will be assessed, and
in whom endocrine, metabolic, and brain imaging measures will be evaluated at eight - ten
month intervals from age eight years (pre-puberty) until age 17 years (post-puberty).
Reproductive endocrine, metabolic, and physical measures will be employed to characterize the
stage and duration of pubertal development. Outcome measures will be derived via multimodal
neuroimaging techniques, cognitive/behavioral assessments, metabolic measurements, and
evaluations of HPA axis function. Additionally, the impact of genetic variation on the
developmental trajectory of these parameters (both reproductive and CNS) will be determined.
This cross-institute proposal will employ a multidisciplinary approach to evaluating the
effects on CNS function of the process of puberty in both boys and girls. This work will not
only serve to inform research on the mechanisms by which sexual dimorphisms in
neuropsychiatric disorders develop, it will also have important implications for the
prevention and treatment of these disorders.
Description:
Despite the clear importance of adolescence in the emergence of a number of disease states
and processes, there is surprisingly little known about how the endocrine and metabolic
events accompanying puberty in humans impact normal developmental neurobiology. Epidemiologic
studies have identified sexual dimorphisms in the prevalence of several neuropsychiatric
disorders, including depression, schizophrenia, and substance abuse. Many of these sex
differences emerge during or shortly after puberty and are maintained until the 5th-6th
decade of life. For example, the two-fold greater risk of unipolar depression in women
compared with men does not appear until adolescence, and prior to puberty girls are not at
increased risk relative to boys. Puberty is a structured, transitional process that can be
influenced by both nutritional factors and environmental stressors; nonetheless, the
variability in the timing and duration of puberty is largely determined by oligogenic
inheritance. Basic neuroscience research has demonstrated that hormonal events accompanying
puberty impact on many of the physiologic systems involved in the regulation of brain
function (e.g., the appearance of new neurons in a brain-region specific pattern, neuronal
remodeling, and the pruning of cortical connectivity). Additionally, not only does stress
during puberty increase the risk of disturbances in affective adaptation during adulthood,
but the events accompanying puberty modify stress responsivity (e.g., alterations in the
duration and peak response of hypothalamic-pituitary-adrenal [HPA] axis hormones to
stressors). Moreover, animal work has demonstrated that neural connectivity differs in a
brain regional specific manner according to the stage of puberty (i.e., early versus late).
In humans, puberty also occurs in stages, and although the endocrinology of puberty,
surprisingly, has not been fully characterized with longitudinal data, studies have
documented that the physical changes measured by Tanner stages I to V are accompanied by
progressive increases in the secretions of both gonadal and adrenal steroids. Nonetheless,
there remains considerable variability in the timing and duration of this otherwise highly
structured reproductive transition.
We propose to perform a longitudinal, naturalistic study examining changes in brain structure
and function, behavior, and stress responsivity in boys and girls across the pubertal
transition. Because the pubertal transition is defined by a complex series of physiologic
events that emerge sequentially over several years and involve changes in multiple endocrine
and growth systems, and because there is also considerable variability in the timing of these
events reflecting the influence of both genetic and environmental factors, puberty cannot by
delineated by age of the participants as has been done in most imaging and other
neurobiological studies of adolescence. The present study will formally bridge this gap by
defining pubertal events per se in participants.
Participants will include healthy boys and girls whose pubertal status will be assessed, and
in whom endocrine, metabolic, and brain imaging measures will be evaluated at eight - ten
month intervals from age eight years (pre-puberty) until age 17 years (post-puberty). We will
screen children in the clinic at age seven however will delay their first regular study visit
until they are eight years old. Reproductive endocrine, metabolic, and physical measures will
be employed to characterize the stage and duration of pubertal development. Outcome measures
will be derived via multimodal neuroimaging techniques, cognitive/behavioral assessments,
metabolic measurements, and evaluations of HPA axis function. Additionally, the impact of
genetic variation on the developmental trajectory of these parameters (both reproductive and
CNS) will be determined.
This cross-institute proposal will employ a multidisciplinary approach to evaluating the
effects on CNS function of the process of puberty in both boys and girls. This work will not
only serve to inform research on the mechanisms by which sexual dimorphisms in
neuropsychiatric disorders develop, it will also have important implications for the
prevention and treatment of these disorders.