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Autism spectrum disorders (ASD) are highly disabling, persistent neurodevelopmental disorders. There are no available treatments for core symptoms of ASD or biologically-based clinical biomarkers. Emerging evidence indicates that levels of brain inflammation are increased in ASD. In particular, recent work implicates hyperactivity of microglial cells, the resident immune cells of the brain. However, the functional consequences of microglial activation remain unknown. This study will measure microglial activation in ASD using positron emission tomography (PET) brain imaging. Adult males with ASD (n=15) and healthy controls (n=15) will be recruited for this study and undergo comprehensive clinical and behavioral baseline assessment. All subjects will then undergo baseline PET imaging using a radiotracer that labels activated microglia. Subjects with ASD will then undergo 12-week open label treatment with minocycline, an FDA-approved antibiotic thought to block microglial activation. PET imaging will be repeated at 12 weeks to confirm target engagement. A subset of control subjects will also undergo repeat PET imaging to determine test-retest reliability. During minocycline treatment, ASD subjects will be evaluated every 2 weeks for safety, clinical impression, behavioral functioning, and measures of cognition. Results will provide important information regarding the relationship between levels of brain inflammation, cognitive and behavioral function in ASD.

Inclusion criteria for participants with ASD

1. Male with a diagnosis of ASD as defined by DSM-5, confirmed by clinical evaluation and ADOS-2.
2. Age 18-35 years inclusive
3. IQ estimate of >70 on VIQ or PIQ
4. Capacity to consent to research
5. Ability to comply with all protocol procedures and assessments
6. Availability of an informant willing to provide information regarding subject behavior and health status (Note: Informant role requires a responsible adult with close, ongoing contact and knowledge of the subject; parent/caregiver acceptable, but not necessary for role)

Exclusion criteria for participants with ASD

1. Evidence of current nicotine, drug, or alcohol abuse or dependence
2. Presence of a chronic medical condition which would potentially influence the assessment of TSPO binding, or interact with study medication (eg. hepatic, neurologic, renal disease) to increase risk to the subject
3. Presence of severe behavioral disturbance likely to require initiation of treatment during the course of the protocol
4. Clinical judgment of the study physician of inability to perform the requirements of the study
5. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, or benzodiazepines
6. Homozygous genotype for minor allele of rs6971
7. History of recent febrile illness in past 30 days
8. History of allergic reactions to tetracycline antibiotics
9. Concomitant medication treatment not stable for the 4 weeks prior to study entry or anticipated to change
10. Current prescribed medication likely to confound assessment of TSPO binding

Inclusion criteria for healthy volunteer participants

1. Male in good general health, confirmed by clinical evaluation
2. Age 18-35 years inclusive
3. IQ estimate of >70 on VIQ or PIQ
4. Ability to comply with all protocol procedures and assessments

Exclusion criteria for healthy volunteer participants

1. Diagnosis of an autism spectrum disorder (ASD)
2. Evidence of current nicotine, drug, or alcohol abuse or dependence
3. Presence of a chronic medical condition which would potentially influence the assessment of TSPO binding, or interact with study medication (eg. hepatic, neurologic, renal disease) to increase risk to the subject
4. Presence of current or lifetime severe psychopathology potentially confounding assessment of TSPO binding (psychosis, severe depression, bipolar disorder, Obsessive-Compulsive Disorder)
5. Current prescribed medication likely to confound assessment of TSPO binding
6. Clinical judgment of the study physician of inability to perform the requirements of the study
7. Current or recent (past 30 days) treatment with minocycline or related compounds, immunosuppressives, benzodiazepines, or psychotropic medications likely to confound assessment of TSPO binding
8. Homozygous genotype for minor allele of rs6971
9. SRS-2 T-score score of >59
10. History of recent febrile illness in past 30 days

IPD will not be shared