Association of Functional Polymorphisms of the Human Tryptophan Hydroxylase 2 Gene With Risk for Bipolar Disorder in Han Chinese

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Abstract
Serotonin (5-hydroxytryptamine) is a neurotransmitter synthesized in the raphe nuclei of the brainstem that controls a wide range of physiological events in the central nervous system.1 Accordingly, disruption of serotonergic function has been implicated in the pathogenesis of many psychiatric disorders, including bipolar disorder (BPD).2-4 The biosynthesis of serotonin is initiated by tryptophan hydroxylase (TPH), using tryptophan as a substrate to generate 5-hydroxytryptophan, followed by decarboxylation using aromatic amino acid decarboxylase to produce serotonin.5 Because TPH is the first as well as the rate-limiting enzyme in the synthetic pathway for serotonin, the TPH gene has been considered a candidate for many behavioral and psychiatric traits.6 Two TPH isoforms encoded by different genes have been identified in humans. The first, TPH1, was discovered earlier and was associated with various neuropsychiatric disorders such as manic-depressive illness,7 depression,8,9 suicidality, and alcoholism.10,11 Despite many reports of positive associations, reports finding no association between TPH1 polymorphisms and many neuropsychiatric disorders have also been published12-14; thus, the role of TPH1 in the development of different neural disorders is still inconclusive.