COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: Effects on the negative symptom response to clozapine

Marta Bosia, Cristina Lorenzi, Adele Pirovano, Carmelo Guglielmino, Federica Cocchi, Marco Spangaro, Placido Bramanti, Enrico Smeraldi, Roberto Cavallaro

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)35-44
Number of pages10
Issue number1
Publication statusPublished - Jan 1 2015


  • clozapine
  • genetic polymorphisms
  • negative symptoms
  • Positive and Negative Symptoms Scale
  • psychopharmacogenetics
  • psychosis
  • schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine
  • Medicine(all)


Dive into the research topics of 'COMT Val158Met and 5-HT1A-R -1019 C/G polymorphisms: Effects on the negative symptom response to clozapine'. Together they form a unique fingerprint.

Cite this