A Study of the Association Between Autism and Immune Changes in the Brain
- People with autism and autism spectrum disorders have problems with communication, behavior, and socializing, and many also have intellectual and developmental disabilities. The cause of autism is not known, but previous research has suggested an association between autism and immune changes in the brain. Researchers are interested in using the experimental radioactive drug (11C)PBR28, which attaches to a protein in the brain that is involved in immune changes, in positron emission tomography (PET) scanning of people with and without autism to see if there are greater immune changes in those with autism.
- To determine if positron emission tomography scanning can be used to evaluate changes in an immune system protein in the brains of people with autism.
- Individuals between 18 and 45 years of age who have been diagnosed with either autism or autism spectrum disorders, or are healthy volunteers.
- Participants will be screened with a physical examination and psychological examination, medical history, questionnaires about behavior and mood, and blood and urine tests.
- Participants will have two imaging studies of the brain at separate study visits. The first study visit will involve a magnetic resonance imaging (MRI) scan to provide a baseline image of the brain. The second study visit will involve PET scan with the radioactive chemical (11C)PBR28 to study immune system proteins in the brain. The MRI scan will take about 40 minutes, and the PET scan will take about 2 hours.
- Participants will have a final study visit 24 hours after the PET scan to provide a final blood sample for testing.
Autism Spectrum Disorders
|Study Design:||Time Perspective: Prospective|
|Official Title:||Neuroimmune Activation in Austism: Imaging Translocator Protein Using Positron Emission Tomography (PET)|
- [11C]PBR28 uptake in brain as measured using VT (volume of distribution) and VT/fp (divided by free fraction in plasma.
- Compare VT in autism versus healthy volunteers
|Study Start Date:||March 4, 2011|
Current estimates indicate that 1 in 110 children are affected with autism. Despite this striking statistic, we remain unable to describe the pathophysiology for autism, and we do not have adequate treatments for autism. The etiologies in most patients with autism are unknown, but emerging evidence supports a causal role of immune activation in autism. Multiple studies provide clear evidence of immune activation in peripheral blood of patients with autism, as demonstrated by elevations in immune markers (IFN-gamma, IL-1RA, IL-6, and TNF-alpha). Studies also demonstrate immune activation in cerebrospinal fluid (CSF) of patients with autism, as evidenced by significant elevations in cytokines and TNF-alpha. Finally, three postmortem brain studies report neuroimmune activation in patients with autism (ages 4-45). Combined, these three postmortem studies show activation of microglia and astroglia through elevations in cytokines, histology and stereology.
While the growing body of literature supporting neuroimmune activation in autism is intriguing, the current results present limitations. First, there are no studies assessing the brains of living patients with autism/ASDs. Second, the most convincing evidence for neuroimmune activation in postmortem brains is extracted almost exclusively from patients with classical autism, where intellectual disability is common. As such, the evidence for neuroimmune activation in higher functioning patients with autism and autism spectrum disorders (ASDs) is less robust.
We propose to determine whether neuroimmune activation is present in the living brains of patients with autism. Furthermore, given the heterogeneity of the autisms , as they are now called, we would like to determine whether neuroimmune activation is detectable in higher versus lower functioning patients with autism/ASDs. We propose to measure neuroimmune activation in the living brains of patients by utilizing positron emission tomography (PET) and the radioligand [(11)C]PBR28. This radioligand binds translocator protein (TSPO), which is over-expressed in activated microglia and reactive astrocytes, and has been demonstrated as a reliable marker of neuroimmune activation in various neuropsychiatric disorders. Because the majority of patients with autism/ASD will require propofol sedation to remain motionless for the two hour scan, we will include a control arm with healthy volunteers without then with propofol in order to determine the effects of propofol on [(11)C]PBR28 uptake. NIH has developed a setup in the clinical center for administering sedation/anesthesia in a safe manner, making this important study possible.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01322555
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Rebecca E Hommer, M.D.||National Institute of Mental Health (NIMH)|