A Study of the Association Between Autism and Immune Changes in the Brain

* INCLUSION CRITERIA: PATIENTS WITH AUTISM OR ASD (INCLUSION CRITERIA): 1. Subjects must have a diagnosis of autistic disorder (299.0) or Asperger s disorder (299.80), as determined using the Diagnostic and Statistical Manual-IV (DSM-IV) and confirmation with the Autism Diagnostic Interview-Revised (Lord 1997) and/or Autism Diagnostic Observation Scale (ADOS). (A diagnosis of Pervasive Developmental Disorder, or PDD, will not suffice for this protocol). 2. Subjects must be adults between 18-45 years old. 3. Subjects must be healthy based on history and physical examination. 4. Subjects must be "binders" to \[11C\]PBR28 as determined via one of two ways: by prior participation in a PET scan with \[11C\]PBR28 or by in vitro testing of their leukocytes. We found that non-binders have markedly reduced affinity of \[3H\]PBR28 to leukocyte membranes. The in vitro binding has shown no overlapping values between binders (\~90%) and non-binders. 5. Subjects must either provide informed consent, or they must assent in combination with informed consent by a legal guardian or durable power of attorney (DPA). HEALTHY VOLUNTEERS (INCLUSION CRITERIA): 1. Subjects must be adults between 18-45 years old. 2. Subjects must be healthy based on history and physical examination 3. Subjects must be binders to \[11 C\]PBR28 (see point 4 above for details) 4. Prior to the PET scan, all healthy subjects must have had within the prior year an MRI scan of the brain to rule out significant structural abnormalities. EXCLUSION CRITERIA: PATIENTS WITH AUTISM OR ASD (EXCLUSION CRITERIA): 1. Any history of alcohol or substance dependence, as these conditions may alter uptake of \[11C\]PBR28. 2. Any history of alcohol or substance abuse within the past 6 months, as these conditions may alter uptake of \[11C\]PBR28. 3. Schizophrenia. 4. In addition to the diagnosis of autistic disorder, ASD or Asperger, any other Axis I disorder that requires inpatient hospitalization during this study, or is at the time of enrollment worsening relative to baseline. We will not completely exclude all Axis I disorders, because it is typical for patients with autism /ASD to carry comorbid Axis I disorders, including Generalized Anxiety Disorder (GAD), social phobia, obsessive compulsive disorder (OCD), dysthymia, Major Depressive Disorder. 5. Intellectual quotient (IQ) less than 30, as including the lowest functioning patients would make the experiment logistically challenging and would broaden heterogeneity too much. 6. Clinically significant laboratory abnormalities as assessed by the PI, medically responsible investigator or consultant. 7. Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases, poorly controlled seizure disorder, or serious cardiopulmonary disease. 8. Active seizure disorder, as defined as having had a seizure in the past year or being on antiepileptic medications for seizures. 9. Positive HIV status. 10. Head trauma resulting in a period of unconsciousness lasting longer than 5 minutes. 11. Exposure to radiation in the past year (i.e., PET from other research), which when combined with this study would be above the allowable limits. 12. Positive urine drug screen at time of enrollment. 13. Pregnancy at time of scan (beta HCG will be measured in all female patients within 24 hours before start of scan and must be negative). 14. In patients who will get an MRI scan at NIH, metallic foreign bodies that would be affected by the MRI magnet, or a fear of enclosed spaces that would prohibit MRI scanning. 15. Allergy to propofol or eggs (since egg products are used to formulate propofol),. 16. Snoring, as this increases the likelihood of complications from propofol sedation. 17. Currently taking antibacterial drugs (such as Amoxicillin-Clavulanate/ Augmentin , Metronidazole/Flagyl Minocycline/Minocin ). We will not discontinue any medications in any subjects. 18. Currently taking antiviral drugs (such as Acyclovir/Zovirax , Interferon beta 1/Avonex , Valacyclovir/Valtrex ). We will not discontinue any medications in any subjects. 19. Taking corticosteroids within the 6 months prior to study enrollment (such as Dexamethasone/Decadron , Hydrocortisone/Hydrocortone , Methylprednisone/Medrol ). We will not discontinue any medications in any subjects. 20. Taking immunosuppressants in the past 6 months prior to study enrollment (such as Azathioprine/Imuran , Infliximab/Remicade , Sulfasalazine/ Azulfidine , Olsalazine/Dipentum ). We will not discontinue any medications in any subjects. 21. Any history of taking immunosuppressants in the context of chemotherapy or organ transplant. Medications in this class might include Tacrolimus/Prograf , 6-mercaptopurine/Purinethol , and Methotrexate/Trexall . We will not discontinue any medications in any subjects. 22. Currently taking Clozapine/Clozaril , as high doses in rats increases TSPO. With the exception of clozapine, patients may be on centrally-acting medications, including medications for mood and behavioral disturbances. These medications may be antiepileptic medications, so long as the antiepileptics are being used for symptoms of mood and behavior as opposed to seizure disorder. Healthy Volunteers (Exclusion criteria): 1. Any past or present Axis I disorder. The exception is substance abuse which ended over 6 months prior to enrollment. 2. Intellectual disability or significant learning problems, as determined by IQ testing lower than 70, inability to read or write, or history of being unable to take regular classes while in school. 3. Clinically significant laboratory abnormalities, as defined as laboratory values that are out of normal range or require clinical workup and/or treatment. 4. With the exception of isolated doses of benzodiazepine which may be administered once or twice by the investigators of this study, psychotropic medication use (including benzodiazepines and illicit drugs) during the 28 days (42 days if fluoxetine) prior to the PET scan. Investigators of this study may administer lorazepam for anxiety (see procedures). 5. Serious medical problems including but not limited to chronic neurological disease such as multiple sclerosis, autoimmune diseases or cardiopulmonary disease that would significantly increase risk with propofol sedation. 6. Positive HIV status. 7. Metallic foreign bodies that would be affected by the MRI magnet or fear of enclosed spaces likely to make the subject unable to undergo an MRI scan. 8. Head trauma resulting in a period of unconsciousness lasting longer than 5 minutes. 9. Exposure to radiation in the past year (i.e., PET from other research), which when combined with this study would be above the allowable limits. 10. Positive urine drug screen at time of enrollment 11. Inability to lie flat on a camera bed for about 2.5 hours per PET scan and 1 hour for MRI. 12. Allergy to propofol or eggs, since egg products are used to formulate propofol 13. Pregnancy at time of scan (beta HCG will be measured in all female patients within 24 hours prior to start of scan and must be negative). 14. Snoring, as this condition increases the likelihood of complications from propofol sedation. 15. Currently taking antibacterial drugs (such as Amoxicillin-Clavulanate/ Augmentin , Metronidazole/Flagyl Minocycline/Minocin ). We will not discontinue any medications in any subjects. 16. Currently taking antiviral drugs (such as Acyclovir/Zovirax , Interferon 1/Avonex , Valacyclovir/Valtrex ). We will not discontinue any medications in any subjects. 17. Taking corticosteroids within the 6 months prior to study enrollment (such as Dexamethasone/Decadron , Hydrocortisone/Hydrocortone , Methylprednisone/Medrol ). We will not discontinue any medications in any subjects. 18. Taking immunosuppressants in the past 6 months prior to study enrollment (such as Azathioprine/Imuran , Infliximab/Remicade , Sulfasalazine/ Azulfidine , Olsalazine/Dipentum ). We will not discontinue any medications in any subjects. 19. Any history of taking immunosuppressants in the context of chemotherapy or organ transplant. Medications in this class might include Tacrolimus/Prograf , 6-mercaptopurine/Purinethol , and Methotrexate/Trexall . We will not discontinue any medications in any subjects.