A Multimodal Imaging Study of Dopamine in Early Psychosis

The development of new treatments for psychosis, a psychiatric condition that is prevalent and highly disabling despite antipsychotic medications, has been limited, in part, by a lack of information from brain imaging studies during the period that leads to the development of psychotic symptoms. In this project the investigators will use Positron Emission Tomography (PET) and neuromelanin-sensitive magnetic resonance imaging (NM-MRI) to examine a brain chemical that is involved in schizophrenia called dopamine and where it first becomes abnormal. The investigators will use multimodal PET/MR imaging (i.e., \[11C\]raclopride w/MPH challenge and NM-MRI) in the same CHR patients. The investigators will recruit 115 clinical high risk individuals. All subjects will undergo \[11C\]raclopride w/methylphenidate challenge and neuromelanin-MRI imaging along with clinical assessments. Patients will be followed every 3 months for two years or until conversion to psychosis, whichever comes first, to assess for conversion to psychosis and clinical outcomes.

Inclusion Criteria: 1. Males or females between 18 and 30 years old 2. Capacity to give informed consent 3. Clinical High Risk (i.e., APSS, GRDS, BIPS) 4. Antipsychotic free for 3 weeks before the PET scan 5. Clinically stable enough for the study Exclusion Criteria: 1. Any substance use disorder, of any severity, within the previous month (before PET scan; not including nicotine or caffeine) 2. Any current use of substance of abuse besides THC/marijuana/cannabis/nicotine/caffeine (on day of PET only) 3. Daily tobacco use 4. Pregnancy 5. Lactation 6. Presence of insulin-dependent diabetes 7. IQ \< 70 (i.e., WTAR \< 6) 8. Acute risk for suicide (i.e., score of 4-5 within the previous month or 6 within the previous 3 months on the CSSRS) or violence, or history of severe violent behavior that may be exacerbated by methylphenidate 9. Presence of metallic objects in the body 10. Lifetime exposure to radiation in the workplace (i.e., being badged for radiation exposure), or exposure to radiation in the context of research protocol within the previous year that exceeds annual limits 11. More than one risk factor for coronary artery disease (e.g., smoking, hyperlipidemia, sedentary lifestyle) 12. Hypertension 13. Presence of clinically significant brain abnormalities. \[For PET Scan Only\] 14. Previous adverse reaction to stimulants that would preclude receiving methylphenidate 15. Presence or positive history of any cardiovascular disease, medical or neurological condition that would preclude methylphenidate administration or participation in this study 16. A history of bipolar disorder Type 1, or any history of syndromal psychosis 17. Lack of effective birth control