OBJECTIVETo investigate the associations between the drug responses to obsessive -pulsive disorder (OCD) and six functional genes related with serotonin and dopamine.

METHODSOne hundred and thirteen OCD nuclear families were collected. The OCD patients were treated with serotonin reuptake inhibitors (SRIs) for 8 weeks and the drug responses were assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). The patients were divided into drug responders group and non-responders group according to the reducing rate of Y-BOCS score. The genotypes of six genes were determined with the Amp-FLP and Amp-RFLP techniques and analyzed by transmission disequilibrium test (TDT). The six genes are serotonin 2A receptor (5-HT2A), serotonin transporter (5-HTT), dopamine D2 receptor ( DRD2), dopamine D4 receptor (DRD4), catechol-O- methyltransferase (COMT) and monoamine oxidase A (MAOA).

RESULTSNo association was found between the six genes and different drug responses groups. However, there was significant difference between the drug responders and non-responders in homozygosity at the 5-HT2A -1438G/A locus (chi(2)=4.69, P=0.03).

CONCLUSIONThe results suggested that the 5-HT2A may play some roles in the effects of drug treatment on OCD.

Adolescent ; Adult ; Catechol O-Methyltransferase ; genetics ; Female ; Humans ; Male ; Monoamine Oxidase ; genetics ; Obsessive-Compulsive Disorder ; drug therapy ; genetics ; Pharmacogenetics ; methods ; Receptor, Serotonin, 5-HT2A ; genetics ; Receptors, Dopamine D2 ; genetics ; Receptors, Dopamine D4 ; genetics ; Serotonin Plasma Membrane Transport Proteins ; genetics ; Serotonin Uptake Inhibitors ; therapeutic use ; Treatment Outcome ; Young Adult

OBJECTIVETo explore the molecular genetic relationship between chromosome 1 and quantitative trait loci for familial schizophrenia.

METHODSA series of assessment scales included positive and negative syndrome scale (PANSS), global assessment of functional scale (GAFS), premorbid schizoid and schizotypal traits scale (PSST), premorbid social adjustment scale (PSA) were applied to quantify the phenotypes of schizophrenia. Non-parametric linkage analysis of quantitative traits was conducted in 32 multiplex pedigrees with schizophrenia by using 29 microsatellite makers on chromosome 1.

RESULTSHaseman-Elston quantitative trait analysis detected a maximum Traditional H-E Lods of 1.73 and a maximum EH H-E Lods of 1.65 of negative symptoms (PANSS-N ) at 147.64 cM, which was overlapped to the positive region of 1q21-23 in qualitative linkage analysis.

CONCLUSIONThe results suggest there might be an independent quantitative trait locus of negative symptoms on 1q21-23 for familial schizophrenia.

Chromosomes, Human, Pair 1 ; genetics ; Family Health ; Genetic Linkage ; Humans ; Lod Score ; Microsatellite Repeats ; Quantitative Trait, Heritable ; Schizophrenia ; genetics

OBJECTIVETo explore the molecular genetic relationship between chromosome 1 and susceptibility genes for familial schizophrenia in Chinese population.

METHODSA genome scanning was conducted in 32 multiplex pedigrees from Chinese population by using 29 microsatellite markers on chromosome 1.

RESULTSMultipoint parametric analysis detected a maximum heterogenicity Lod of 1.70 at 262.52 cM under a recessive model; multipoint non-parametric analysis detected a maximum non-parameter linkage (NPL) of 1.71 (P=0.046) at 262.52 cM, then 1.37 (P=0.086) at 149.70 cM, corresponding to marker D1S206 and D1S425 respectively.

CONCLUSIONThese results give further supports to the presence of susceptibility genes on chromosome 1q for familial schizophrenia.

Adult ; China ; Chromosome Mapping ; Chromosomes, Human, Pair 1 ; genetics ; Family Health ; Female ; Genetic Linkage ; Genetic Predisposition to Disease ; genetics ; Humans ; Lod Score ; Male ; Microsatellite Repeats ; Middle Aged ; Models, Genetic ; Pedigree ; Schizophrenia ; genetics

Purpose: The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells. Materials and Methods ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments. Results CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib. Conclusion Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.

Purpose: The potential of members of the epidermal growth factor receptor (ErbB) family as drug targets in cholangiocarcinoma (CCA) has not been extensively addressed. Although phase III clinical trials showed no survival benefits of erlotinib in patients with advanced CCA, the outcome of the standard-of-care chemotherapy treatment for CCA, gemcitabine/cisplatin, is discouraging so we determined the effect of other ErbB receptor inhibitors alone or in conjunction with chemotherapy in CCA cells. Materials and Methods ErbB receptor expression was determined in CCA patient tissues by immunohistochemistry and digital-droplet polymerase chain reaction, and in primary cells and cell lines by immunoblot. Effects on cell viability and cell cycle distribution of combination therapy using ErbB inhibitors with chemotherapeutic drugs was carried out in CCA cell lines. 3D culture of primary CCA cells was then adopted to evaluate the drug effect in a setting that more closely resembles in vivo cell environments. Results CCA tumors showed higher expression of all ErbB receptors compared with resection margins. Primary and CCA cell lines had variable expression of erbB receptors. CCA cell lines showed decreased cell viability when treated with chemotherapeutic drugs (gemcitabine and 5-fluorouracil) but also with ErbB inhibitors, particularly afatinib, and with a combination. Sequential treatment of gemcitabine with afatinib was particularly effective. Co-culture of CCA primary cells with cancer-associated fibroblasts decreased sensitivity to chemotherapies, but sensitized to afatinib. Conclusion Afatinib is a potential epidermal growth factor receptor targeted drug for CCA treatment and sequential treatment schedule of gemcitabine and afatinib could be explored in CCA patients.