br Methods br Results br Discussion To

Methods
Results
Discussion To our knowledge, this is the first report to investigate the association between DBH genotype and pDβH activity in Han Chinese subjects. We also examined the relationship among DBH gene polymorphisms, pDβH activity and cognitive function in patients with schizophrenia. We had three main findings: (1) There was a significant association between pDβH activity and DBH gene polymorphism, rs1611115, which account for 12.6% of the variance in pDβH activity. (2) There was a nominal positive correlation between cognitive improvement in VFT and pDβH activity in patients with schizophrenia after 8weeks of treatment. (3) There was a significant association between the rs1108580 genotype and VFT score in this sample. As in subjects of European origin, rs1611115 explained the largest proportion of variance in pDβH activity, however, in subjects of African Americans, rs1611115 accounts for a lower proportion of the variance in pDβH activity than in subjects of European origin (Tang et al., 2005, Tang et al., 2006, Tang et al., 2007, Zabetian et al., 2001). In the present study, rs1611115 also accounted for a lower proportion of the variance in pDβH activity in Han Chinese. Previous studies found that AA genotype at rs1108580 was significantly associated with lower pDβH activity (Cubells et al., 1998), but this association was not replicated in our sample. The two DBH polymorphisms examined in this study have been found to be in strong LD in prior reports (Bhaduri and Mukhopadhyay, 2008, Zabetian et al., 2003). Zabetian and colleagues identified a single 10-kb block containing rs1611115 and rs1108580, in which four haplotypes comprised 93% of the observed AT7519 (Zabetian et al., 2003). On the contrary, absence of LD between these two polymorphisms was also reported in an Indian sample (Das et al., 2011). In the present study, strong LD was found between rs1611115 and rs1108580 even though there was relatively weak predictive value of one genotype to another (i.e., D′=1.0, but r2=0.034). One possible explanation for this result could be the absence of the T-G haplotype in our study. This low T-G haplotype frequency produces a high D′ but low r2 in LD analysis. DBH converts DA to NE, and both transmitters appear to be involved in cognitive regulation in schizophrenia (Condray and Yao, 2011, Sakurai et al., 2013). We found no correlation between age, education attainment, cognitive performance and pDβH activity. However, there was a nominal positive correlation between the VFT score increase after 8-weeks therapy and pDβH activity, subjects with a higher pDβH activity performed better on VFT. This may suggest that pDβH activity could be predictive of the improvement in verbal fluency after antipsychotic therapy. To the degree that pDβH predicts cognitive function in the brain, it might indicate higher conversion of DA to NE, with a resulting reduction in the DA/NE ratio in the brain. Such a change could alter the balance between dopaminergic and noradrenergic systems in the brain, which may in turn alter cognitive performance (Arnsten, 2011, Cubells and Zabetian, 2004). However, it is worth mentioning that this result was not consistent with the study of van Kammen et al. (1994), which found low levels of DβH in CSF significantly associated with good social and sexual functioning, good prognosis, less symptoms between hospitalizations, and excellent clinical response to neuroleptic treatment. The inconsistent findings of cognitive deficits may be due to multiple and complex factors, including race, age, gender, education, smoking status, antipsychotic drug treatment and different cognitive assessments. Longitudinal studies of large samples of patients will be needed to resolve these issues.