PET study of [(18)F]6-fluoro-L-dopa uptake in neuroleptic- and mood-stabilizer-naive first-episode nonpsychotic mania: effects of treatment with divalproex sodium.
OBJECTIVE
Although dopaminergic hyperactivity has been implicated in mania, the precise location in the brain of the abnormality is unclear. This study assessed presynaptic dopamine function in neuroleptic- and mood-stabilizer-naive nonpsychotic first-episode manic patients before and after treatment with divalproex sodium by measuring [(18)F]6-fluoro-L-dopa ([(18)F]DOPA) uptake in the striatum with positron emission tomography (PET).


METHODS
Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [(18)F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2-6 weeks after beginning treatment with divalproex sodium monotherapy. [(18)F]DOPA uptake rate constants (K(i) values) in the striatum were calculated by using graphical analysis with activity from the occipital cortex as the input function.


RESULTS
No significant differences in [(18)F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, [(18)F]DOPA rate constants were significantly reduced in the patients and were lower in the patients than in the comparison subjects.


CONCLUSIONS
Although presynaptic dopamine function as reflected by [(18)F]DOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.
Yatham
Lakshmi N
LN
Department of Psychiatry, University of British Columbia, Vancouver, Canada. yatham@unixg.ubc.ca
Liddle
Peter F
PF
Shiah
I-Shin
IS
Lam
Raymond W
RW
Ngan
Elton
E
Scarrow
Gayle
G
Imperial
Miguel
M
Stoessl
Jon
J
Sossi
Vesna
V
Ruth
Thomas J
TJ
D000328:Adult; D000367:Age Factors; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D014150:Antipsychotic Agents; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D008875:Middle Aged; D014055:Tomography, Emission-Computed / Q000706:statistics & numerical data; D014635:Valproic Acid / Q000627:therapeutic use*
D000927:Anticonvulsants; D014150:Antipsychotic Agents; D005462:Fluorine Radioisotopes; C043437:fluorodopa F 18; D014635:Valproic Acid; D004295:Dihydroxyphenylalanine; D004298:Dopamine