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Serotonin (5-hydroxytryptamine [5-HT]) is a neurotransmitter synthesized in the raphe nuclei of the brain stem in the central nervous system (CNS) and also in the periphery. Dysfunction of the serotonergic system has been implicated in the pathogenesis of psychiatric disorders. Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in 5-HT biosynthesis. For more than a decade, only one gene encoding TPH was identified in vertebrates. Recently, a second TPH gene, designated TPH2, was detected, located on human chromosome 12, a susceptibility region for affective disorders. TPH2 is predominantly expressed in the brain, whereas the classical TPH gene, TPH1, is expressed in peripheral tissues. The discovery of the brain-abundant TPH2 gene justifies a new concept of the CNS serotonergic system. TPH2, rather than TPH1, has now become a candidate gene for 5-HT-related affective disorders. We compared TPH2 mRNA levels in postmortem parietal cortex of unipolar-depressed, bipolar, and schizophrenic patients vs control subjects, using real-time reverse transcription polymerase chain reaction. No significant difference in TPH2 mRNA levels was found among the four diagnostic groups. The lack of difference might suggest that this gene is not involved in the etiology of of these psychiatric disorders. Alternatively, it is possible that the parietal cortex is not the relevant brain area involved in the pathophysiology of these disorders or that posttranscriptional modifications of TPH2 mRNA occur in these patients, causing changes in protein levels and/or enzymatic activity. |
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