Context:The tryptophan hydroxylase 2 (TPH2) gene encodes the first (also the rate-limiting) enzyme in the serotonin biosynthetic pathway. Despite reports of possible associations between polymorphisms in human TPH2 and many psychiatric disorders, including bipolar disorder (BPD), the functional effect and susceptibility loci of such polymorphisms for BPD have not yet been identified. Objectives:To examine the association of TPH2 with BPD and to identify the functional variants that may be involved in the pathophysiological development of BPD.Design, Setting, and Patients: We systematically screened all exons and promoters of the TPH2 gene in Han Chinese subjects to identify sequence variants. Association tests were conducted in 105 cases and 106 control subjects using single-locus, linkage disequilibrium, and haplotype analyses. Two promoter and one exon 2 single-nucleotide polymorphisms were examined for their functional role using a reporter gene system and enzyme activity assay, respectively. Additional statistical analysis was performed to study the interaction between the 2 TPH genes in 205 study participants with TPH1 and TPH2 genotype data.Results: Significant haplotype association of TPH2 polymorphisms and BPD was identified (P Ͻ.001). In addition, allelic alteration of polymorphisms in the promoter region and exon 2 of TPH2 caused noteworthy functional losses in promoter and enzyme activities, respectively, indicating the potential susceptibility loci for BPD. We found that the odds ratio changed from 3.73 of the TAG haplotype to 4.81 or 1.68, depending on the combined effect of both TPH genotypes. These data suggested an interaction between the 2 TPH genes to confer a risk for BPD.Conclusions: This study supports the involvement of TPH2 in the etiology of BPD, and the functional singlenucleotide polymorphisms identified herein might be the susceptibility loci for BPD. Although the interaction between the 2 TPH genes merits further investigation, our findings suggest that the interactive effect should be considered in future studies of serotonin-related disorders.

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Despite the low prevalence of MDD in Taiwanese adults, the pattern of low help-seeking behavior and profound functional impairment indicates much room for improvement in the early detection of and intervention in major depression in this population.

Disaster workers are at high risk for developing psychiatric morbidity. This study examined the prevalence rates of psychiatric and posttraumatic distress and the relationship between psychiatric and posttraumatic morbidity and coping strategies among rescue workers following an earthquake in Taiwan on September 21, 1999. Eighty-four male firefighters who had been exposed to earthquake rescue work were assessed 5 months after the event. The Chinese Health Questionnaire (CHQ), the Impact of Event Scale (IES), and the Ways of Coping Questionnaire (WCQ) were used to assess psychiatric morbidity, posttraumatic morbidity, and coping strategies. The observed prevalence rates were 16.7% and 21.4% for general psychiatric morbidity and posttraumatic morbidity, respectively. Results from multivariate logistic regression indicated that job experience and confrontive coping were significant predictors of psychiatric morbidity, while job experience, distancing, escape-avoidance, and positive reappraisal were significant predictors of posttraumatic morbidity. Rescue workers with longer job experience were at the highest risk for developing psychiatric and posttraumatic distress.

SUMMARY Alzheimer’s disease (AD) is a progressive condition that affects cognition, function, and behavior. Approximately 60–90% of patients with AD develop neuropsychiatric symptoms (NPS) such as hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep disturbances, appetite and eating changes, or altered sexual behavior. These noncognitive behavior changes are thought to result from anatomical and biochemical changes within the brain, and have been linked, in part, to cholinergic deficiency. Cholinesterase inhibitors may reduce the emergence of NPS and have a role in their treatment. These agents may delay initiation of, or reduce the need for, other drugs such as antipsychotics. This article summarizes the effects of donepezil, a cholinesterase inhibitor, on the NPS of dementia with emphasis on AD and dementia with Lewy bodies.