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- 5-HIAA, 5-hydroxyindoleacetic acid
- 5-HT, 5-hydroxytryptamine
- ARMS, amplification refractory mutation system
- BPD, bipolar affective disorder
- cAMP, cyclic adenosine monophosphate
- MSBE, multiple single base extension approach
- PCR-ASO, PCR allele specific oligonucleotide
- SNPs, single nucleotide polymorphisms
Bipolar affective disorder (BPD), a common severe mood disorder characterised by manic and depressive episodes, has an estimated lifetime prevalence of 0.1%–1% in various populations, including that of Taiwan.1 Although previous studies have strongly suggested the involvement of genetic factors in the aetiology of BPD, the search for predisposing genes using classical linkage analysis has been fraught with difficulty. Association studies have been shown to be effective in mapping genes for complex diseases and have therefore been widely applied to studies of many psychiatric traits, including BPD.2,3 The results suggest that several genes with minor effects might be involved in the pathogenesis of BPD and that genes involved in neurotransmitter metabolism or signal transduction are possible candidates for an association with BPD.3–5
Serotonin (5-hydroxytryptamine; 5-HT), a major neurotransmitter in the central nervous system, is involved in various physiological events, such as mood control, sleep, thermoregulation, learning, and memory.6 Disruption of serotonergic function has been implicated in the pathogenesis of many psychiatric disorders, including BPD.7,8 Serotonin exerts its diverse functions through multiple receptor (HT receptor; HTR) subtypes.9 These receptors, localised on the post- or pre-synaptic neuronal membrane, bind released serotonin and either transmit the signal to the post-synaptic neurone or regulate serotonin production by the neurone itself. Seven classes of HTRs (HTR1–7), made up of 15 functionally and pharmacologically distinct receptor subtypes,10,11 have been identified in mammalian species in the past few years. Except for HTR3, which is a ligand gated ion channel receptor, all known HTR family members are guanine nucleotide binding protein (G-protein) coupled receptors.
Of these 15 subtypes, several, which are abundantly expressed in the limbic system and have a high affinity for antipsychotic drugs, are related to mood control.12 Studies on knockout or transgenic mice …