PubMed:25560469 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/25560469","sourcedb":"PubMed","sourceid":"25560469","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/25560469","text":"COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: effects on the negative symptom response to clozapine.\nAIM: Clozapine is still considered the gold standard for treatment-resistant schizophrenia patients; however, up to 40% of patients do not respond adequately. Identifying potential predictors of clinical response to this last-line antipsychotic could represent an important goal for treatment. Among these, functional polymorphisms involved in dopamine system modulation, known to be disrupted in schizophrenia, may play a role. We examined the COMT Val158Met polymorphism, which plays a key role in dopamine regulation at the prefrontal level, and the 5-HT1A-R -1019 C/G polymorphism, a target of clozapine activity involved in the interaction between the serotonin and dopamine systems.\nMATERIALS \u0026 METHODS: 107 neuroleptic-refractory, biologically unrelated Italian patients (70 males and 37 females) with a DSM-IV diagnosis of schizophrenia who were being treated with clozapine were recruited. Psychopathology was assessed by the Positive and Negative Symptoms Scale (PANSS) at the beginning of treatment, and at weeks 8 and 12. Genomic DNA was extracted from venous blood samples. COMT rs4680 (Val158Met) and 5-HT1A-R rs6295 (-1019 C/G) polymorphisms were analyzed by PCR-based restriction fragment length and direct sequencing, respectively.\nRESULTS: We found a significant effect of COMT and 5-HT1A-R on the PANSS Negative Subscale variation, with greater improvement among COMT Val/Val and 5-HT1A-R G/G subjects.\nCONCLUSION: The findings support the hypothesis that COMT rs4680 and 5-HT1A-R rs6295 polymorphisms could influence the negative symptom response to clozapine, probably through modulation of the dopaminergic system.","tracks":[{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":185,"end":198},"obj":"HP_0100753"},{"id":"T2","span":{"begin":505,"end":518},"obj":"HP_0100753"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubmedHPO"},{"subj":"T2","pred":"source","obj":"PubmedHPO"}]},{"project":"PubTator4TogoVar","denotations":[{"id":"53","span":{"begin":1200,"end":1206},"obj":"SNP"},{"id":"55","span":{"begin":1232,"end":1238},"obj":"SNP"},{"id":"61","span":{"begin":1588,"end":1594},"obj":"SNP"},{"id":"62","span":{"begin":1608,"end":1614},"obj":"SNP"}],"attributes":[{"id":"A53","pred":"resolved_to","subj":"53","obj":"tmVar:rs4680;VariantGroup:0;CorrespondingGene:1312;RS#:4680;CorrespondingSpecies:9606"},{"id":"A55","pred":"resolved_to","subj":"55","obj":"tmVar:rs6295;VariantGroup:1;CorrespondingGene:3350;RS#:6295;CorrespondingSpecies:9606"},{"id":"A61","pred":"resolved_to","subj":"61","obj":"tmVar:rs4680;VariantGroup:0;CorrespondingGene:1312;RS#:4680;CorrespondingSpecies:9606"},{"id":"A62","pred":"resolved_to","subj":"62","obj":"tmVar:rs6295;VariantGroup:1;CorrespondingGene:3350;RS#:6295;CorrespondingSpecies:9606"},{"subj":"53","pred":"source","obj":"PubTator4TogoVar"},{"subj":"55","pred":"source","obj":"PubTator4TogoVar"},{"subj":"61","pred":"source","obj":"PubTator4TogoVar"},{"subj":"62","pred":"source","obj":"PubTator4TogoVar"}]},{"project":"PubTatorOnTogoVar","denotations":[{"id":"53","span":{"begin":1200,"end":1206},"obj":"SNP"},{"id":"55","span":{"begin":1232,"end":1238},"obj":"SNP"},{"id":"61","span":{"begin":1588,"end":1594},"obj":"SNP"},{"id":"62","span":{"begin":1608,"end":1614},"obj":"SNP"},{"id":"T1","span":{"begin":1200,"end":1206},"obj":"SNP"},{"id":"T2","span":{"begin":1232,"end":1238},"obj":"SNP"},{"id":"T3","span":{"begin":1588,"end":1594},"obj":"SNP"},{"id":"T4","span":{"begin":1608,"end":1614},"obj":"SNP"}],"attributes":[{"id":"A53","pred":"resolved_to","subj":"53","obj":"tmVar:rs4680;VariantGroup:0;CorrespondingGene:1312;RS#:4680;CorrespondingSpecies:9606"},{"id":"A55","pred":"resolved_to","subj":"55","obj":"tmVar:rs6295;VariantGroup:1;CorrespondingGene:3350;RS#:6295;CorrespondingSpecies:9606"},{"id":"A61","pred":"resolved_to","subj":"61","obj":"tmVar:rs4680;VariantGroup:0;CorrespondingGene:1312;RS#:4680;CorrespondingSpecies:9606"},{"id":"A62","pred":"resolved_to","subj":"62","obj":"tmVar:rs6295;VariantGroup:1;CorrespondingGene:3350;RS#:6295;CorrespondingSpecies:9606"},{"id":"A1","pred":"resolved_to","subj":"T1","obj":"tmVar:rs4680;VariantGroup:0;CorrespondingGene:1312;RS#:4680;CorrespondingSpecies:9606"},{"id":"A2","pred":"resolved_to","subj":"T2","obj":"tmVar:rs6295;VariantGroup:1;CorrespondingGene:3350;RS#:6295;CorrespondingSpecies:9606"},{"id":"A3","pred":"resolved_to","subj":"T3","obj":"tmVar:rs4680;VariantGroup:0;CorrespondingGene:1312;RS#:4680;CorrespondingSpecies:9606"},{"id":"A4","pred":"resolved_to","subj":"T4","obj":"tmVar:rs6295;VariantGroup:1;CorrespondingGene:3350;RS#:6295;CorrespondingSpecies:9606"},{"subj":"53","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"55","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"61","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"62","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T1","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T2","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T3","pred":"source","obj":"PubTatorOnTogoVar"},{"subj":"T4","pred":"source","obj":"PubTatorOnTogoVar"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"PubmedHPO","color":"#ec93cd","default":true},{"id":"PubTator4TogoVar","color":"#93e8ec"},{"id":"PubTatorOnTogoVar","color":"#ecd693"}]}]}}