Several limitations of this study need to be acknowledged
Several limitations of this study need to be acknowledged. First, although 200 patients were recruited into this study and completed assessments at baseline, only 89 patients completed the cognitive tests after 8weeks of treatment. The relatively long study period (8weeks) was the main reason for the high dropout rate, as many patients were discharged in fewer than 8weeks. Second, only two polymorphisms, rs1611115 and rs1108580 were studied. Though the role of DBH rs1611115 in pDβH activity is well documented, other DBH polymorphisms may also be important. Third, we did not control the type and dose of antipsychotic medications. However, our analysis of covariance did not provide evidence of an effect of olanzapine-equivalent dose on our findings.
In summary, we found that DBH gene polymorphisms, rs1611115 was significantly associated with pDβH activity with TT Levofloxacin kinase associated with lower pDβH activity. In addition, we found this polymorphism alone accounted for 0.126 of pDβH activity in Chinese patients with schizophrenia, lower than that reported in other populations. We also found evidence to support the association between the rs1108580 variant and poor VFT performance in schizophrenia, suggesting a specific role of that polymorphism (or more likely, a functional variant in LD with it) in some aspects of cognitive function. Further studies including other genetic polymorphisms of the DBH gene with larger sample sizes are required to clarify the relationship of the dopamine metabolism and cognitive function.
Role of funding source This project was funded by the National Natural Science Fund of China (Grant no. 81071082) and Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (Grant no. ZYLY 201403).
Contributors Yi-Lang Tang, Wen-Biao Li, Pei-Xian Mao, Yun Ma and Zuo-Li Sun were responsible for study design, statistical analysis and manuscript preparation. Yun Ma, Xue Yang and Pei-Xian Mao were responsible for recruiting the patients, performing the clinical rating and collecting the samples. Zuo-Li Sun, Jing He and Jun Li were responsible for the DBH activity assay and DBH genotyping. Yi-Lang Tang was involved in editing the manuscript and providing the funding for the study. Joseph F. Cubells were involved in editing the manuscript. All authors have contributed to and have approved the final manuscript.
Conflict of interest
Introduction Personality traits have been shown to be highly heritable and relatively stable over the life-span (Bouchard et al., 1990, Roberts and DelVecchio, 2000). Inspired by biologically oriented theories on personality, psychiatry research has acknowledged the predictive power of personality traits for psychopathological disorders (Grabe, Spitzer, & Freyberger, 2004). The basic idea is that phenotypic variability in healthy subjects and patients suffering from mental illness have the same biological underpinnings (Montag et al., 2012, Montag and Reuter, 2014). This continuum model covers the full range from the normal to psychopathology and has been supported by numerous studies (e. g. Van Os, Linscott, Myin-Germeys, Delespaul, & Krabbendam, 2009). The biosocial personality theory of psychiatrist Robert Cloninger was most influential for paving the way for the idea that personality traits can predispose for psychopathology (Cloninger, Svrakic, & Przybeck, 1993). Cloninger suggested that personality can be best described by four temperaments (novelty seeking, harm avoidance, reward dependence, and persistence) and three character dimensions (self-directedness, cooperativeness and self-transcendence). Temperaments should have a strong genetic basis whereas character dimensions are influenced by learning mechanisms in social contexts. With respect to the temperaments he made clear statements on their biological basis (Cloninger, 1987a). Of relevance for the present study, reward dependence (RD) is thought to be associated with low activity of the noradrenergic neurotransmitter system. RD, also called the behavioral maintenance system, is characterized by resistance to extinction of previously rewarded behavior (Cloninger, 1987b). Subjects scoring high on RD are marked by sentimentality, attachment and dependence (especially on the opinion of others). Biochemical studies supported the hypothesis of a link between RD and the noradrenergic system. For example, Curtin et al. (1997) reported that monoamine levels explained 44% of the variance of RD in healthy male participants. RD correlated significantly with urinary epinephrine and 3-methoxy-4-hydroxyphenylglycol (MHPG; a metabolite of epinephrine and norepinephrine) levels (r=0.51 and r=0.50, respectively).