TY - JOUR
T1 - COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms
T2 - Effects on the negative symptom response to clozapine
AU - Bosia, Marta
AU - Lorenzi, Cristina
AU - Pirovano, Adele
AU - Guglielmino, Carmelo
AU - Cocchi, Federica
AU - Spangaro, Marco
AU - Bramanti, Placido
AU - Smeraldi, Enrico
AU - Cavallaro, Roberto
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Aim: 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. Materials & 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. Results: 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. Conclusion: 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. Original submitted 26 February 2014; Revision submitted 15 October 201.
AB - Aim: 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. Materials & 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. Results: 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. Conclusion: 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. Original submitted 26 February 2014; Revision submitted 15 October 201.
KW - clozapine
KW - genetic polymorphisms
KW - negative symptoms
KW - PANSS
KW - Positive and Negative Symptoms Scale
KW - psychopharmacogenetics
KW - psychosis
KW - schizophrenia
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UR - http://www.scopus.com/inward/citedby.url?scp=84920854903&partnerID=8YFLogxK
U2 - 10.2217/pgs.14.150
DO - 10.2217/pgs.14.150
M3 - Article
C2 - 25560469
AN - SCOPUS:84920854903
VL - 16
SP - 35
EP - 44
JO - Pharmacogenomics
JF - Pharmacogenomics
SN - 1462-2416
IS - 1
ER -