PET Scanning in Parkinson's Disease

This is an in vivo positron emission tomography (PET) study of regional cerebral dopamine neurochemistry and blood flow in normal volunteers, persons with Parkinson's disease (both familial and sporadic), and those with schizophrenia spectrum disorders. The latter also sign consent for NIH approved protocol 89-M-0160, "Inpatient Evaluation of Neuropsychiatric Patients," PI: Jose Apud, M.D., Ph.D. Using PET with 6-[F-18] Fluoro-L-dopa (FDOPA) and (15)0-H(2)O in a single scan session, both presynaptic dopaminergic function and regional cerebral blood flow (rCBF) are assessed. The kinetic rate constant (Ki) for presynaptic dopaminergic uptake in striatum and other regions is calculated. Using analysis of Ki, we compare Ki across subject groups and relate the findings to rCBF. Cerebral findings are also related to allelic variation in genes of interest, for determination of which participants sign separate consent for NIH approved protocol 95-M-0150 "Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings," PI: Daniel Weinberger, M.D.). We also draw comparisons between subjects with inherited vs. sporadic Parkinson's disease to determine whether the PET phenotype is the same in both groups, and we compare system-level, circuit-based pathophysiology across PD and schizophrenia groups. Each subject is further screened with an MRI to rule out structural abnormalities and also to further delineate areas of interest in the PET scans.

This is a positron emission tomography (PET) study of regional cerebral dopamine neurochemistry and blood flow in normal volunteers, patients with Parkinson's disease (both familial and sporadic), and those with schizophrenia spectrum disorders. The latter also sign consent for NIH approved protocol 89-M-0160, "Inpatient Evaluation of Neuropsychiatric Patients," PI: Jose Apud, M.D., Ph.D. Using PET with 6-[F-18] Fluoro-L-dopa (FDOPA) and (15)0-H(2)O in a single scan session, both presynaptic dopaminergic function and regional cerebral blood flow (rCBF) are assessed. The kinetic rate constant (Ki) for presynaptic dopaminergic uptake in striatum and other regions is calculated. We compare Ki across subject groups and relate the findings to rCBF. Findings are also related to allelic variation in genes of interest, for determination of which participants sign separate consent for NIH approved protocol 95-M-0150 "Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and Their Siblings," PI: Daniel Weinberger, M.D.). We also draw comparisons between subjects with inherited vs. sporadic Parkinson's disease to determine whether the PET phenotype is the same in both groups, and we compare system-level, circuit-based pathophysiology across PD and schizophrenia groups. Each subject is further screened with an MRI to rule out structural abnormalities and also to further delineate areas of interest in the PET scans.

• Gasser T, Muller-Myhsok B, Wszolek ZK, Oehlmann R, Calne DB, Bonifati V, Bereznai B, Fabrizio E, Vieregge P, Horstmann RD. A susceptibility locus for Parkinson's disease maps to chromosome 2p13. Nat Genet. 1998 Mar;18(3):262-5.
• Kitada T, Asakawa S, Hattori N, Matsumine H, Yamamura Y, Minoshima S, Yokochi M, Mizuno Y, Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605-8.
• Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997 Jun 27;276(5321):2045-7.

• INCLUSION CRITERIA:
• Age between 18 and 90 years
• Ability to give informed consent
• Ability to read and write
• Ability to give adequate medical and neuropsychiatric history.

PARKINSONS DISEASE:

• Individuals over the age of 18 from families in which an autosomal dominant form of Parkinson's disease is suspected based on pedigree analysis.
• Each subject will have a medical history and brief neurological examination.
• The diagnosis in probands must be supported by accepted clinical criteria: tremor, bradykinesia, and responsiveness to L-DOPA.
• Equivocally affected individuals will also be included in order to aid in their phenotypic classification as will at risk individuals who show no neurological signs.
• Individuals with sporadic Parkinson's disease will also be scanned. These will be over the age of 50 years and will have no known family history of Parkinson's disease or any other movement disorder.
• PD patients will have an admission physical exam and medical history as well as laboratory tests deemed necessary on the basis of history and physical exam.

SCHIZOPHRENIA:

- Members of this patient group will have a diagnosis of schizophrenia or schizophrenia spectrum disorder as determined by the SCID and will be currently enrolled in NIH approved protocol 89-M-0160 (Inpatient Evaluation of Neuropsychiatric Patients) under which they will have received admission work-up.

HEALTHY VOLUNTEERS:

• A large cohort of healthy volunteers will also have a PET scan.
• Volunteers will be age, gender and handedness-matched to patients for statistical purposes.
• Volunteers, who are enrolled as healthy controls under protocol 95-M-0150 "Neurobiological Investigation of Patients with Schizophrenia Spectrum Disorders and their Siblings" will receive admission workup through that protocol.

EXCLUSION CRITERIA:

• Will include medical illness that would affect cerebral blood flow or dopamine
• Current pregnancy
• Current breast feeding
• Possible exposure to radiation exceeding RSC guidelines
• History of addiction to alcohol or drugs
• Inability to stay caffeine- and nicotine-free for 4 hours
• Current suicidality or assaultiveness
• History of movement disorder
• History of head injury requiring hospitalization
• History of coma
• Inability to meet general safety criteria for MRI study (as determined by standardized Nuclear Medicine Research (NMR) Center screening)
• Previously demonstrated inability or unwillingness to comply with a study protocol.

PARKINSONS DISEASE:

- Individuals not capable of understanding the consent will be excluded.

HEALTHY VOLUNTEERS:

• Healthy volunteers will be unable to participate if they have been treated with psychotropic medication within the three months prior to scanning
• Undergoing current psychiatric treatment
• History of major psychiatric disorder
• Have a first degree relative with schizophrenia
• Have a family history of PD