Exploring Gene-Treatment Interactions: Dissociated Effect of COMT Val108/158Met Genotype on Negative Symptoms Response to Haloperidol and Risperidone Vs Clozapine(In Press)

Research in Genetics

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Marta Bosia1, Adele Pirovano2, Cristina Lorenzi3, Federica Cocchi4, Carmelo Guglielmino5, Marco Spangaro6, Placido Bramanti7, Enrico Smeraldi8 and Roberto Cavallaro9



1,3,4,5,8,9Department of Clinical Neurosciences, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy

1Center for Neurolinguistics & Theoretical Syntax (NeTS), Institute for Advanced Study, (IUSS), Pavia, Italy

2,6,8Università Vita-Salute San Raffaele, Milan, Italy

7I.R.C.C.S. Centro Neurolesi “Bonino Pulejo”, Messina, Italy

Volume 2014(2014), Article ID 184831, Research in Genetics, 17 pages, DOI:

Received date : 30 July 2014; Accepted date : 17 October 2014; Published date : 4 November 2014

Academic editor: Vera E. Golimbet


Aims: this study aims to evaluate the effect of COMT rs 4680 (Val108/158Met) polymorphism, known to regulate dopamine levels, on specific response pattern to antipsychotics characterized by different dopaminergic activity. 2 Materials and Methods: the sample included 153 subjects diagnosed with schizophrenia, treated either with haloperidol, risperidone or clozapine. Clinical evaluation with PANSS scale was assessed at the beginning of treatment and at week eight. All patients underwent genetic analysis for the polymorphism of interest. Results: at week 8 we found a significant genotype-treatment interaction for PANSS Negative subscale variation. Among patients on haloperidol and risperidone, the improvement was greater for carriers of Met allele, while in the clozapine group a greater improvement was observed for Val/Val genotype. Conclusions: our results, although preliminary, suggest that COMT Val/Val genotype could represent a biological marker for treatment with clozapine in subjects with prominent negative features.

Keywords: Schizophrenia and psychosis; Genetics; Psychopharmacogenetics; Antipsychotics, Clozapine.