Effects of Adolescent Synaptic Pruning
Trial Snapshot
- Phase
- Not Applicable
- Status
- Enrolling By Invitation
- Sponsor
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Non-invasive quantification of synaptic pruning
Study Overview
Brief Summary
The study will use a PET-based measure of brain cell (neuron) connections (synapses) in young adults who have also obtained an MRI, to assess how the loss of brain cell connections (synaptic pruning) is captured by MRI-based measures. This will inform youth MRI studies to understand neurotypical brain development that can help identify abnormal trajectories as in mental illness.
Detailed Description
The loss of brain cell (neuron) connections (synapses) through human development, known as synaptic pruning, has been characterized in postmortem studies but how this proceeds in live humans as they age into adulthood is not well understood. This study will use the PET tracer [11C]UCB-J which provides a direct measure of synaptic density, in conjunction with previously acquired ultra-high field MRI, in a group of young adults in order to understand how standard MRI-based measures reflect changes in the density of synapses. PET [11C]UCB-J is known to measure the density of synaptic connections by measuring a protein (SV2A) present in synapses. A comparison of results from the current study with MRI-based measures of byproducts of synaptic membrane breakdown from childhood to early adulthood will allow assessment of how non-invasive MRI reflects synaptic pruning through development, facilitating studies of how the brain changes through adolescence and into adulthood, which is needed to identify patterns of development associated with the emergence of mental illness.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Males or females between 18-26 years of age, AND currently enrolled in the Parent Project (R01MH067924)
Exclusion Criteria
- •(these exclusion criteria are outlined in the Parent Project)
- •Head injury with loss of consciousness over an hour.
- •A vision problem or eye movement problem (such as lazy eye, double vision, blurred vision, or color blindness).
- •A learning disability and/or ever had an Individualized Education Plan (IEP) in school.
- •Significant neurological or metabolic illness: Epilepsy, Meningitis, Encephalitis, Diabetes, Huntington's disease.
- •Diagnosed with a psychiatric disorder.
- •Participants with, or with a first degree relative, having a DSM IV Axis l psychiatricdisorder.
- •Metal implants or ferromagnetic objects contained within the body which may interfere with the MRI scan (but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord, or cochlear implant.) Dental fillings do not present a risk for MRI. If there is a possibility of metal being present in the participant's body, the participant will be excluded from the study.
- •Weight more than 250 pounds.
- •Claustrophobia or uncomfortable in small spaces.
- •<70% on the Achenbach scale (either from Youth Self Report (YSR) or Adult Self Report (ASR)).
- •IQ < 80 or IQ >
- •Pregnancy or lactation, lack of effective birth control during 15 days before the scans.
- •Currently employed as radiation worker; or participation in radioactive drug research protocols within the previous year such that the total cumulative annual radiation dose (i.e., from participation in the previous radioactive drug study [studies] and this study) would exceed the radiation dose limits specified in the FDA regulations (i.e., 21 CFR 361.1) that govern the research use of [C-11]UCB-J
- •History of drug or alcohol abuse (from parent study eligibility).
Arms & Interventions
PET Imaging Supplemental Component
Adult participants enrolled in the parent study, will be given the option to be a part of the PET imaging supplemental project. Maximum enrollment is 60 adult participants. Interested participants will be consented into the PET portion, and will have a single PET scan (as outlined in the Study Description section).
Intervention: PET Imaging Scan using [11C]UCB-J (Radiation)
Outcomes
Primary Outcomes
Non-invasive quantification of synaptic pruning
Time Frame: The PET-CT scan will be within approximately 30 days of the parent study MRI.
1\. Age-related changes in synaptic density through young adulthood o Cross-sectional age-related (18-26 years of age) changes in synaptic density via SUVR quantified within the dorsolateral prefrontal cortex.
Secondary Outcomes
No secondary outcomes reported
Investigators
Beatriz Luna
Professor
University of Pittsburgh