Imaging Dopamine D2 Agonist Binding Sites in Schizophrenia
Imaging Dopamine D2 Agonist Binding Sites in Schizophrenia
The goals of this study is to determine (1) if differences in D2/3 receptor affinity states
 exist between medication-free subjects with SCH (MF-S) compared with healthy controls (HC),
 (2) the degree to which pre- and post-synaptic factors contribute to increased striatal
 dopamine (DA) signaling in MF-S and (3) to test the hypotheses that optimal DA transmission
 in the dorsal caudate (DCA) is necessary for normal working memory (WM) function.
An antagonist ([11C]raclopride) and agonist ([11C]NPA) radiotracer will be used sequentially,
 in a counterbalanced design, to measure binding potential (BPND) under baseline conditions
 and 3-hours following oral administration of 0.5 mg/kg amphetamine in the same 30 MF-S and 30
 HC. The main outcome measures will be baseline BPND and the percent change in BPND induced by
 amphetamine, denoted ∆BPND, in the subdivisions of the striatum. In addition, all subjects
 will undergo fMRI while performing a WM task concurrent with both the initial pre- and
 initial post-amphetamine PET scans to explore the relationship between DCA DA transmission
 and fMRI BOLD response in the dorsal lateral prefrontal cortex (DLPFC) during a WM task.
Inclusion Criteria:

 -  HEALTHY CONTROLS

 1. Males or females between 18 and 35 years old (History)

 2. Absence of current (i.e. last six months) psychiatric conditions (including
 alcohol and drug abuse). Subjects with a history of a non-psychotic psychiatric
 disorder who have been asymptomatic and not taking medication for the past 6
 months may be eligible.

 (History, SCID-NP (non-patient version))

 3. A negative urine toxicology with the exception of cannabis; in the case of a
 positive urine cannabis test a salivary cannabis test will be administered on the
 day of the PET scans to ensure subjects have not used within 24 - 48 hours.

 (Urine toxicology)

 4. Medically Healthy (History, EKG, physical, labs (detailed labs are listed under
 screening procedures))

 5. Weight between 44 and 115 kg (physical exam)

 6. Baseline systolic BP of < 150 and > 100, diastolic BP < 90 and >60 and baseline
 HR less than 90 (Physical exam)

 -  SUBJECTS WITH SCHIZOPHRENIA Criteria (Assessment)

 1. Males or females between 18 and 35 years old (History)

 2. Fulfill DSM-V criteria for schizophrenic illness, schizophreniform or
 schizoaffective disorder (History, SCID)

 3. A negative urine toxicology with the exception of cannabis; in the case of a
 positive urine cannabis test a salivary cannabis test will be administered on the
 day of the PET scans to ensure subjects have not used within 24 - 48 hours.

 (Urine toxicology)

 4. Medically Healthy (History, EKG, physical, labs (detailed labs are listed in
 screening procedures))

 5. Clinical Global Impression-Severity scale (CGI-S) less than or equal to 4
 (moderately ill).

 6. Off all medications for at least 1 week, does not wish to restart medications
 immediately and clinically stable while off medications. With the exception of
 lorazepam at a maximal dose of 2 mg QD, up to 24 h prior to the scans, and
 absence of injection of depot medication within the last 6 months (Interview and
 discussion with treating clinician)

 7. Weight between 44 and 115 kg (Physical exam)

 8. Baseline systolic BP of < 150 and > 100, diastolic BP < 90 and >60 and baseline
 HR less than 90 (Physical exam)

 Exclusion Criteria:

 -  HEALTHY CONTROLS

 1. Pregnancy or lactation, lack of effective birth control during 15 days before the
 scans* (Blood or Urine pregnancy test, history)

 2. Presence or positive history of serious medical or neurological illness,
 including low hemoglobin and seizure history.

 (Medical and neurological history, EKG, blood tests)

 3. Any current use (within past month) of amphetamines, opiates, cocaine,
 sedative-hypnotics, ecstasy PCP.

 (History, urine toxicology)

 4. Any use of cannabis beyond occasional use (i.e. more than 2 - 4 times per month)
 (History, saliva cannabis test)

 5. Metal implants or paramagnetic 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), as determined in consultation with a
 neuroradiologist and according to the guidelines set forth in the following
 reference book commonly used by neuroradiologists: "Guide to MR procedures and
 metallic objects" Shellock, PhD, Lippincott Williams and Wilkins, NY 2001. If
 there is any doubt, subjects will be excluded.

 (Interview and history)

 6. Lifetime exposure to radiation in the workplace; or participation in research
 protocols involving exposure to radiation within the previous year such that the
 total cumulative annual radiation dose (i.e., from participation in the previous
 research studies and this study) would exceed the radiation dose limits specified
 in the FDA regulations at 21 CFR 361.1, Radioactive Drugs Considered Generally
 Safe and Effective (i.e. annual cumulative radiation dose limit = 5 rems to
 gonads, blood-forming organs, lens of eye, whole body; 15 rems to other organs).

 (Interview and history)

 7. Medical history of chronic obstructive pulmonary disease or other chronic
 respiratory disorders (Medical history)

 8. More than one risk factor for coronary artery disease (smoking, cholesterol > 240
 mg/dl, sedentary lifestyle) baseline SBP > 140 of DBP> 90) (History, physical
 examination and blood chemistry)

 9. Positive Allen Test indicating lack of collateral flow to hand (Physical Exam)

 10. Subjects with family history of a psychotic disorder, drug and alcohol
 Abuse/Dependence in first-degree relatives. (History)

 -  SUBJECTS WITH SCHIZOPHRENIA Criteria (Assessment)

 1. DSM-V disorder other than schizophrenia, schizophreniform or schizoaffective
 disorder (History, SCID)

 2. Any current use (within past month) of amphetamines, opiates, cocaine,
 sedative-hypnotics, ecstasy PCP.

 (History, urine toxicology)

 3. Any use of cannabis beyond occasional use (i.e. more than 2 - 4 times per month)
 (History, saliva cannabis test)

 4. Antipsychotic medications in the last 3 weeks (6 months for depot medications)
 prior to the first PET scanning session.

 (History)

 5. Pregnancy or lactation, lack of effective birth control - OCP are allowed.
 (Pregnancy test, history)

 6. Presence or positive history of severe medical or neurological illness or any
 cardiovascular disease, low hemoglobin, and seizure history.

 (Medical and neurological history, neurological exam, EKG, blood chemistry)

 7. Lack of capacity to give informed consent (Interview)

 8. History of significant violent or suicidal behavior (Interview and review of
 records)

 9. Metal implants or paramagnetic 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), as determined in consultation with a
 neuroradiologist and according to the guidelines set forth in the following
 reference book commonly used by neuroradiologists: "Guide to MR procedures and
 metallic objects" Shellock, PhD, Lippincott Williams and Wilkins, NY 2001. If
 there is any doubt, subjects will be excluded.

 (Interview and history)

 10. Lifetime exposure to radiation in the workplace; or participation in research
 protocols involving exposure to radiation within the previous year such that the
 total cumulative annual radiation dose (i.e., from participation in the previous
 research studies and this study) would exceed the radiation dose limits specified
 in the FDA regulations at 21 CFR 361.1, Radioactive Drugs Considered Generally
 Safe and Effective (i.e. annual cumulative radiation dose limit = 5 rems to
 gonads, blood-forming organs, lens of eye, whole body; 15 rems to other organs).

 (Interview and history)

 11. Medical history of chronic obstructive pulmonary disease or other chronic
 respiratory disorders (Medical history)

 12. More than one risk factor for coronary artery disease (smoking, cholesterol > 240
 mg/dl, sedentary lifestyle) baseline SBP > 140 of DBP> 90) (History, physical
 examination and blood chemistry)