PET Study of [¹⁸F]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 [¹⁸F]6-fluoro-l-dopa ([¹⁸F]DOPA) uptake in the striatum with positron emission tomography (PET). METHOD: Thirteen patients with DSM-IV bipolar I disorder, manic episode, and 13 healthy comparison subjects underwent [¹⁸F]DOPA PET scans. Ten of the 13 patients had repeat PET scans 2–6 weeks after beginning treatment with divalproex sodium monotherapy. [¹⁸F]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 [¹⁸F]DOPA uptake rate constants in the striatum were found between the manic patients and the comparison subjects. After treatment with divalproex sodium, [¹⁸F]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 [¹⁸F]DOPA uptake is not altered in mania, presynaptic dopamine function in manic patients was lower after treatment with divalproex sodium.