In vivo measurement of the vesicular monoamine transporter in schizophrenia.
Given evidence for excessive striatal dopamine activity in schizophrenia, we sought to test the hypothesis that dopaminergic innervation in the striatum is abnormally elevated, and a secondary hypothesis that age-related loss is accelerated. Twelve schizophrenic subjects on stable doses of medications, along with 12 age and sex-matched healthy control subjects, underwent positron emission tomography (PET) studies with [11C]dihydrotetrabenazine (DTBZ), which binds to the vesicular monoamine transporter, type 2 (VMAT2). DTBZ binding reflects principally dopaminergic projections in the striatum and appears in animal models, over treatment periods as long as two weeks, not to be regulated by antipsychotic drugs. Using an equilibrium analysis, we obtained measurements of the binding potential (BP) of [11C]DTBZ, as well as a transport (K(1)) measure, corresponding to regional cerebral blood flow. BP in the striatum showed no difference between the patient and control groups, and no differential effect of age. We did not find evidence supporting the hypothesis that excessive dopamine activity in schizophrenia could be explained by increased density of striatal dopamine terminals.
Taylor
S F
SF
Departments of Psychiatry, University of Michigan, Ann Arbor, MI 48109-0118, USA.
Koeppe
R A
RA
Tandon
R
R
Zubieta
J K
JK
Frey
K A
KA
D000293:Adolescent; D000328:Adult; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002250:Carbon Radioisotopes; D018450:Disease Progression; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000706:statistics & numerical data; D008297:Male; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D011869:Radioligand Assay; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013747:Tetrabenazine / Q000031:analogs & derivatives / Q000494:pharmacology; D014055:Tomography, Emission-Computed; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D002250:Carbon Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; C493452:SLC18A2 protein, human; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D004298:Dopamine; D013747:Tetrabenazine