Investigating how puberty affects brain development and health

A Longitudinal Investigation of the Endocrine and Neurobiologic Events Accompanying Puberty

This study is trying to see how puberty affects brain development and health in healthy kids aged 8 by looking at changes in their brain function over time.

Quick facts

• Study type: Observational
• Enrollment: 370 (estimated)
• Ages: 7 Years to 35 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT01434368 on ClinicalTrials.gov

What this trial studies

This observational study aims to explore the endocrine and neurobiological changes that occur during puberty and their impact on normal brain development. By utilizing functional magnetic resonance imaging (fMRI), researchers will assess how hormonal changes influence brain function and the emergence of neuropsychiatric disorders. The study will involve healthy child volunteers aged 8 years, who will be monitored over time to understand the natural history of puberty and its effects on neurodevelopment. The findings could provide insights into the timing and nature of puberty-related changes in brain structure and function.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy children aged 8 years with normal IQ and growth patterns.

Not a fit: Patients with significant neurological or cognitive disorders may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance our understanding of puberty's role in the development of neuropsychiatric disorders, potentially leading to better prevention and treatment strategies.

How similar studies have performed: While there have been studies on puberty and neurodevelopment, this specific longitudinal approach using fMRI to investigate these changes is relatively novel.

Eligibility criteria

* INCLUSION CRITERIA - SAMPLE 1:

Child volunteers will qualify for inclusion if they meet the following criteria:

* Good general health and normal IQ; A normal IQ will be determined by the scores on Test of Irregular Word Reading Efficiency (TIWRE)
* Age 8 years;
* Body Mass Index (kg/m\^2) between the 15th and 85th percentiles for age and sex according to the US Centers for Disease Control and Prevention 2000 growth charts;
* A normal tempo of growth as determined by skeletal age within +/- 1.64 standard deviations of chronologic age according to the Greulich and Pyle radiographic atlas (i.e., no evidence for precocious puberty or abnormal delay of maturation); Research criteria for determining bone age will be performed by the collaborating pediatric endocrinologist. This criterion is required only for the initial entry into this study and is not one of the inclusion criteria for subsequent visits;
* No history of significant neurologic or cognitive disorders. Examples include neonatal anoxic encephalopathy, seizure disorders, autism, and most learning disorders including attention deficit hyperactivity disorder;
* Able to provide assent. Parents will provide consent.
* Able to speak and read English.

EXCLUSION CRITERIA - SAMPLE 1:

Child volunteers will be excluded for the following reasons:

* Presence of any medical condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in eye or other body part, dental braces);
* Presence or history of medical conditions known to affect cerebral anatomy;
* Children who are not pre-pubertal as indicated by the presence of Tanner stage 2 development (i.e., areolar development in girls and testicular volume \> 3 cc in boys);
* Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or any other condition which, in the opinion of the investigators, would impede the ability to give informed consent or possibly hinder completion of the study; presence of any psychiatric disorder in the subject, sibling, or other first-degree relative;
* Subjects who regularly use prescription medications (the use of over-the-counter medications will be reviewed on a case-by-case basis.);
* For females who have reached menarche: Pregnancy, lactation, or inability or unwillingness to undergo pregnancy testing (a urine pregnancy test will be performed prior to all MRI and X-ray procedures for girls who have had the onset of menses);
* Current or past use of psychiatric medication;
* I.Q. \< 70 (determined by the scores on Test of Irregular Word Reading Efficiency \[TIWRE\]).

INCLUSION CRITERIA - SAMPLE 2:

Child volunteers will qualify for inclusion if they meet the following criteria:

* Good general health and normal IQ; A normal IQ will be determined by the scores on Test of Irregular Word Reading Efficiency (TIWRE)
* Ages 12-13 years;
* Body Mass Index (kg/m\^2) between the 15th and 85th percentiles for age and sex according to the US Centers for Disease Control and Prevention 2000 growth charts;
* A normal tempo of growth as determined by skeletal age within +/- 1.64 standard deviations of chronologic age according to the Greulich and Pyle radiographic atlas (i.e., no evidence for precocious puberty or abnormal delay of maturation); Research criteria for determining bone age will be performed by the collaborating pediatric endocrinologist. This criterion is required only for the initial entry into this study and is not one of the inclusion criteria for subsequent visits.;
* No history of significant neurologic or cognitive disorders. Examples include neonatal anoxic encephalopathy, seizure disorders, autism, and most learning disorders including attention deficit hyperactivity disorder;
* Able to provide assent. Parents will provide consent.
* Able to speak and read English.

EXCLUSION CRITERIA - SAMPLE 2:

Child volunteers will be excluded for the following reasons:

* Presence of any medical condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in eye or other body part, dental braces);
* Presence or history of medical conditions known to affect cerebral anatomy;
* Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or any other condition which, in the opinion of the investigators, would impede the ability to give informed consent or possibly hinder completion of the study; presence of any psychiatric disorder in the subject, sibling, or other first-degree relative;
* Subjects who regularly use prescription medications (the use of over-the-counter medications will be reviewed on a case-by-case basis.);
* For females who have reached menarche: Pregnancy, lactation, or inability or unwillingness to undergo pregnancy testing (a urine pregnancy test will be performed prior to all MRI and X-ray procedures for girls who have had the onset of menses);
* Current or past use of psychiatric medication;
* I.Q. \< 70 (determined by the scores on Test of Irregular Word Reading Efficiency \[TIWRE\]).

INCLUSION/EXCLUSION CRITERIA - SAMPLE 3:

Inclusion and exclusion criteria for sample 3 will be identical as those for sample 2 with the exception that children between the ages of 8 and 17 will be included.

INCLUSION/EXCLUSION CRITERIA - SAMPLE 4:

Sample 4 participants will also be volunteering in Protocol #95-M-0150 Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings, and/or Protocol #81-M-0126, The Evaluation of Women with Menstrually-Regulated Mood and Behavioral Disorders, in which they will also have signed consent and through which they will have been screened.

INCLUSION CRITERIA - SAMPLE 4:

* Ages of 25 to 35 years at the time of enrollment.
* Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
* No use of psychotropic substances in the last 3 months.
* No psychiatric or severe chronic medical illness at the time of the study, and by history.
* Able to speak and read English.

EXCLUSION CRITERIA - SAMPLE 4:

* Presence of impaired hearing.
* Pregnant or currently breast feeding. (a urine pregnancy test will be performed prior to MRI procedures in women).
* Presence of a history head trauma with loss of consciousness in the last year or any evidence of functional impairment due to and persisting after head trauma.
* Previous eye surgery with a prosthetic implant.
* Participants with tattoos will be excluded if the tattoos are in a location on the body (eyes, lips, etc.) that could interfere with fMRI scans or contain a heavy metal content.
* Presence of any non-organic implant or any other device such as: cardiac pacemaker, insulin infusion pump, implanted drug infusion device, cochlear, otologic, or ear implant, transdermal medication patch (Nitro), any metallic implants or objects, body piercing(s), bone/joint pin, screw, nail, plate, wire sutures or surgical staples, shunt.
* Presence of cerebral or other aneurysm clips.
* Presence of shrapnel or other metal imbedded in the body (such as from war wounds or accidents).
* Previous employment in metal fields or with machines that may have left any metallic fragments in or near the eyes.
* History of a severe accident in the past that may possibly have left metal in the body.
* Psychological contraindications for MRI (e.g., suffer from claustrophobia);
* Less than an 8th grade education or an IQ below 70 as determined by the scores on Test of Irregular Word Reading Efficiency \[TIWRE\] .

INCLUSION/EXCLUSION CRITERIA - SAMPLE 5:

Inclusion and exclusion criteria for sample 5 will be identical as those for samples 1 and 2 (i.e., children will either be age 8-9 or between the ages of 12 and 13) with the exception that children with a tempo of growth that is considered abnormal as demonstrated by skeletal age greater than two standard deviations in advance of their chronologic age according to the Greulich and Pyle Radiographic Atlas will be included. These children will be matched for age, Tanner stage, race, ethnicity, and BMI with children currently enrolled in the longitudinal study.

SAMPLE 6

Participants will have participated in this protocol as children in either Sample 1 or sample 2.

INCLUSION CRITERIA:

* Age 19 to 30 years at the time of re-enrollment.
* Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document.
* Normal physical exam, routine labs and absence of axis 1 psychiatric illnesses as confirmed by a Structured Diagnostic Interview for DSM-5 (SCID).
* No current use of psychotropic substances.

EXCLUSION CRITERIA:

* Presence of any implant or medical condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in eye or other body part, dental braces);
* Presence or history of medical conditions known to affect cerebral anatomy;
* Individuals who have current substance abuse or a psychiatric disorder or any other condition which, in the opinion of the investigators, would impede the ability to give informed consent or possibly hinder completion of the study;
* Current use of psychiatric medication or presence of any psychiatric disorder;
* For females: pregnancy, lactation, or inability or unwillingness to undergo pregnancy testing (a urine pregnancy test will be performed prior to all MRI procedures);

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Peter J Schmidt, M.D. — National Institute of Mental Health (NIMH)
• Study coordinator: Peter J Schmidt, M.D.

Conditions fMRI; Functional Magnetic Resonance Imaging; Normal Development; Puberty; Natural History; Healthy Volunteer; HV