Yatham for a review). Neuroendocrine studies have reported unaltered prolactin responses to buspirone and dl-fenfluramine, growth hormone responses to sumatriptan, blunted prolactin responses to d-fenfluramine and enhanced cortisol responses to ipsapirone and 5-hydroxytryptophan in people with mania

of serotonin (5-hydroxytryptamine, 5-HT) in major depression, the precise nature of alterations in the 5-HT system that underlie manic symptoms still remains elusive. For instance, the studies of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) levels, platelet 5-HT uptake or tritiated imipramine binding sites in people with mania have yielded inconsistent results (see Shiah & Yatham for a review). Neuroendocrine studies have reported unaltered prolactin responses to buspirone and dl-fenfluramine, growth hormone responses to sumatriptan, blunted prolactin responses to d-fenfluramine and enhanced cortisol responses to ipsapirone and 5-hydroxytryptophan in people with mania compared with healthy controls. Taken together, these studies suggest a reduction in presynaptic 5-HT activity, enhanced postsynaptic 5-HT1A receptor and likely 5-HT2 receptor sensitivity, and unaltered 5-HT1D receptor sensitivity in mania. 4 These studies, however, were limited by the fact that they provide information about 5-HT activity in the hypothalamic region only and not in other brain regions. Although numerous positron emission tomography (PET) studies have assessed brain 5-HT2 receptors in people with major depression, no study to date measured brain 5-HT2 receptors in people with acute mania. The purpose of the present study, therefore, was to assess brain 5-HT2 receptor density in drug-free or drug-naive people with acute mania in comparison with healthy individuals using [F]setoperone with PET.