Chul Soo Park

Body Weight and Plasma Levels of Ghrelin and Leptin during Treatment with Olanzapine

Although enhanced appetite and weight gain are potential side effects of treatment with antipsychotic agents, particularly olanzapine and clozapine, the mechanisms underlying these side effects are poorly understood. Leptin and ghrelin were recently identified as hormones that play crucial roles in the regulation of energy balance and glucose metabolism. To elucidate relationships between weight change and plasma levels of ghrelin and leptin, we investigated the circulating ghrelin and leptin levels and body weight during olanzapine treatment. Twenty-four patients with schizophrenia were examined during 6-month administration of olanzapine. Ghrelin, leptin, weight and body mass index (BMI) were measured before and after 2, 4, 8, 12, 16, and 24 weeks of olanzapine treatment. The concentration of glucose and various lipid metabolic parameters were measured at baseline and at 24 weeks. Significant increases in weight, BMI and leptin were observed at week 24. On the other hand, the serum levels of ghrelin decreased significantly after olanzapine treatment. In addition, the level of ghrelin was negatively correlated with the leptin level, BMI and weight. The leptin level was positively correlated with both BMI and weight. Ghrelin is associated with metabolic changes, in combination with leptin, during olanzapine treatment. However, further large-scale and longitudinal studies are warranted to elucidate the metabolic changes involving ghrelin, leptin and insulin during treatment with antipsychotics.

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using χ2 analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (Pcorr = 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

Association of ZDHHC8 polymorphisms with smooth pursuit eye movement abnormality.

The zinc finger DHHC domain‐containing protein 8 (ZDHHC8) is located in the 22q11 microdeletion region and may contribute to the behavioral deficit associated with 22q11 deletion syndrome. Although polymorphisms of ZDHHC8 have been reported to be associated with the risk of schizophrenia, those associations are still controversial. This study was performed to validate the genetic association of ZDHHC8 polymorphisms with the risk of schizophrenia, and also to scrutinize the association with smooth pursuit eye movement (SPEM) abnormality in a Korean population. Five SNPs of ZDHHC8 were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using allele‐based χ2 analyses. Association of ZDHHC8 polymorphisms with SPEM abnormality among 166 schizophrenic patients were analyzed using multiple regressions. No ZDHHC8 polymorphisms were found to be associated with the risk of schizophrenia. However, four SNPs and one haplotype (ht4) were strongly associated with the risk of SPEM abnormality even after multiple correction (P = 0.00005–0.0007, Pcorr = 0.0001–0.002). The results of the present study provide the first evidence that ZDHHC8 on the 22q11 locus might have influence on SPEM function of schizophrenia patients in a Korean population and may provide a new clue for understanding differential effects of candidate genes in schizophrenia.

Luteimonas marina sp. nov., isolated from seawater

A marine bacterial strain, designated FR1330(T), was isolated from a seawater sample collected near Ganghwa Island, the Republic of Korea. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain FR1330(T) belonged to the Gammaproteobacteria and was related to the genus Luteimonas; its closest neighbours were the type strains of Luteimonas composti (97.9 % sequence similarity) and Luteimonas mephitis (95.0 %). DNA-DNA relatedness values for strain FR1330(T) with Luteimonas composti CC-YY255(T) and Luteimonas mephitis KACC 11391(T) were 33 and 10 %, respectively. Cells of strain FR1330(T) were Gram-negative, aerobic, rod-shaped and oxidase- and catalase-positive. The predominant respiratory lipoquinone was ubiquinone-8. The major fatty acids were branched-chain saturated iso-C(15 : 0) (26.2 %) and unsaturated iso-C(17 : 1)omega9c (26.0 %). The DNA G+C content was 67.6 mol%. On the basis of several phenotypic characteristics, strain FR1330(T) could be differentiated from Luteimonas composti and Luteimonas mephitis. The data obtained from the polyphasic study demonstrated clearly that strain FR1330(T) represents a novel species of the genus Luteimonas. The name Luteimonas marina sp. nov. is proposed, with strain FR1330(T) (=KCTC 12327(T)=JCM 12488(T)=IMSNU 60306(T)) as the type strain.

Association analysis of G72/G30 polymorphisms with schizophrenia in the Korean population.

Several studies examining the association between G72/G30 polymorphisms and schizophrenia in cohorts of various ethnic origins have recently been reported. The aim of the current study was to examine the genetic influence of the G72/G30 polymorphisms in the Korean population. Nine G72/G30 single-nucleotide polymorphisms (SNPs) were genotyped in 388 patients with schizophrenia and 367 normal controls from the Korean population. Based on statistical analyses, the positive associations of previous studies of other populations were not replicated in the present study. However, 2 of the 9 tested SNPs, rs778294 and rs947267, were found to be associated with the risk of schizophrenia after correction for multiple testing (P(cor)=0.03 and P(cor)=0.04, respectively). The rs778294 SNP, taken singly, had not been found to be associated with schizophrenia in previous studies, and the second SNP, rs947267, showed an opposite direction of genetic effect on schizophrenia risk here than in a previous study. Our association results were not consistent with those found in other populations, and, thus could be chance findings. Therefore, further studies with larger sample sizes are needed to confirm a risk allele for this gene if it exists.

Association of RANBP1 haplotype with smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder and smooth pursuit eye movement (SPEM) disturbance is proposed as one of the most consistent neurophysiological endophenotype in schizophrenia. The aim of this study was to examine the genetic association of RANBP1 polymorphisms with the risk of schizophrenia and with the risk of SPEM abnormality in schizophrenia patients in a Korean population. Two SNPs of RANBP1 were genotyped by TaqMan assay. Their genetic effect of single/haplotype polymorphisms on the risk of schizophrenia and SPEM abnormality from 354 patients and 396 controls were performed using χ2 and multiple regression analyses. Although no RANBP1 polymorphisms were associated with the risk of schizophrenia, a common haplotype, RANBP1‐ht2 (rs2238798G–rs175162T), showed significant association with the risk of SPEM abnormality among schizophrenia patients after multiple correction (Pcorr = 0.002–0.0003). The results of present study provide the evidence that RANBP1 on 22q11.21 locus might be causally related to the SPEM abnormality rather than the development of schizophrenia.

Sphingopyxis rigui sp. nov. and Sphingopyxis wooponensis sp. nov., isolated from wetland freshwater, and emended description of the genus Sphingopyxis.

Two yellow-pigmented, Gram-reaction-negative strains, designated 01SU5-P(T) and 03SU3-P(T), were isolated from the freshwater of Woopo wetland, Republic of Korea. Both strains were aerobic, non-motile and catalase-negative. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two isolates belong to the genus Sphingopyxis, showing the highest level of sequence similarity with respect to Sphingopyxis witflariensis W-50(T) (95.4-95.7 %). The two novel isolates shared 99.4 % sequence similarity. DNA-DNA hybridization between the isolates and the type strain of S. witflariensis clearly suggested that strains 01SU5-P(T) and 03SU3-P(T) represent two separate novel species in the genus Sphingopyxis. The two strains displayed different fingerprints after PCR analysis using the repetitive primers BOX, ERIC and REP. Several phenotypic characteristics served to differentiate these two isolates from recognized members of the genus Sphingopyxis. The data from the polyphasic study presented here indicated that strains 01SU5-P(T) and 03SU3-P(T) should be classified as representing novel species in the genus Sphingopyxis, for which the names Sphingopyxis rigui sp. nov. and Sphingopyxis wooponensis sp. nov., respectively, are proposed. The type strain of Sphingopyxis rigui sp. nov. is 01SU5-P(T) ( = KCTC 23326(T) = JCM 17509(T)) and the type strain of Sphingopyxis wooponensis sp. nov. is 03SU3-P(T) ( = KCTC 23340(T) = JCM 17547(T)).

Genetic association analysis of ERBB4 polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population.

The human receptor tyrosine-protein kinase erbB-4 (ERBB4) gene mediates neuregulin 1 (NRG1) signaling, and is involved in neuronal migration and differentiation. Despite the potential significance of ERBB4 in the development of schizophrenia, relatively few genetic studies for the association of ERBB4 with schizophrenia were performed in the populations including Ashkenazi Jews, Americans including Caucasians and African Americans, and Han Chinese. In this study, differences in ERBB4 variations were investigated to determine association with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Seven polymorphisms in ERBB4 gene were genotyped in 435 schizophrenia cases and 390 unrelated healthy controls. In order to investigate the relationship between ERBB4 and the risk of schizophrenia and SPEM abnormality, differences in SNP and haplotype distribution were analyzed using logistic and multiple regression analyses. However, we failed to replicate the associations reported by previous studies in other populations. Although statistically not significant, the tendency towards associations between ERBB4 polymorphisms and the risk of schizophrenia and SPEM abnormality in this study from a Korean population would be helpful for further genetic etiology studies in schizophrenia.

Genetic association analysis of CNR1 and CNR2 polymorphisms with schizophrenia in a Korean population.

Located on 6q15 and 1p36.11, cannabinoid receptor 1 (CNR1) and cannabinoid receptor 2 (CNR2) genes are considered to be a positional and functional candidate gene for the development of mental disorders such as schizophrenia because CNR1 is known as a regulator of dopamine signaling in the hippocampus and the cerebral cortex. However, few genetic studies have been carried out to investigate an association of CNR1 and CNR2 polymorphisms and the risk of schizophrenia. In this study, although the result indicates that CNR1 and CNR2 variations are unlikely to influence schizophrenia susceptibility in a Korean population, the findings would provide meaningful information for further genetic studies.

Neuregulin 3 does not confer risk for schizophrenia and smooth pursuit eye movement abnormality in a Korean population

Located on chromosome 10q22‐q23, the human neuregulin3 (NRG3) is considered to be a strong positional and functional candidate gene for schizophrenia pathogenesis. Several case–control studies examining the association of polymorphisms in NRG3 with schizophrenia and/or related traits such as delusion have been reported recently in cohorts of Han Chinese, Ashkenazi Jews, Australians and white Americans of Western European ancestry. Thus, this study aimed to comprehensively investigate the association of NRG3 genetic variations with the risk of schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Using TaqMan assay, six single‐nucleotide polymorphisms (SNPs) in the intronic region of NRG3 were genotyped and two major haplotypes were identified in 435 patients with schizophrenia as cases and 393 unrelated healthy individuals as controls. A total of 113 schizophrenia patients underwent an eye tracking task, and degree of SPEM abnormality was measured using the logarithmic values of the signal/noise (Ln S/N) ratio. Differences in frequency distributions were analyzed using logistic and regression models following various modes of genetic inheritance and controlling for age and sex as covariates. Subsequent analysis revealed that the frequency distributions of NRG3 polymorphisms and haplotypes were similar between schizophrenia patients and healthy controls of Korean ethnicity. Furthermore, no significant differences were observed between the genetic variants tested for SPEM abnormality. By elucidating a lack of association in a Korean population, findings from this study may contribute to the understanding of the genetic etiology focusing on the role of NRG3 in schizophrenia pathogenesis.