title: Factors affecting cognitive remediation response in schizophrenia: the role of COMT gene and antipsychotic treatment.
abstract: Cognitive remediation is the best available tool to treat cognitive deficits in schizophrenia and has evidence of biological validity; however results are still heterogeneous and significant predictors are lacking. Previous studies showed that cognitive remediation is able to induce changes in PFC function and dopaminergic transmission and thus the study of possible sources of variability at these levels (i.e. antipsychotic treatments and genetic variability) might help to gain a deeper understanding of neurobiological correlates and translate into optimization and personalization of interventions. In the present study, we analyzed the interaction between pharmacological treatment (clozapine vs typical/atypical D2 blockers) and COMT rs4680 polymorphism on cognitive changes after cognitive remediation therapy, in a sample of 98 clinically stabilized patients with schizophrenia. The General Linear Model showed a significant interaction of pharmacological treatment and COMT polymorphism on the improvement in "Symbol Coding" subtest, a global measure of speed of processing. Post-hoc analysis revealed a significant difference between COMT genotypes, when treated with D2 blockers, with worse results among Val/Val patients. These preliminary results suggest that genetic variability, influencing prefrontal dopamine, might affect individual capacity to improve with different patterns, depending on antipsychotic treatment.
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy; Institute for Advanced Study, IUSS, Center for Neurolinguistics and Theoretical Syntax (NeTS), Pavia, Italy. Electronic address: bosia.marta@hsr.it.
authors.forename: Marta
authors.initials: M
authors.lastname: Bosia
authors.affiliation: Università Vita -Salute San Raffaele, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanoletti
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy; Università Vita -Salute San Raffaele, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Spangaro
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: Mariachiara
authors.initials: M
authors.lastname: Buonocore
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: Margherita
authors.initials: M
authors.lastname: Bechi
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Cocchi
authors.affiliation: Università Vita -Salute San Raffaele, Milan, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Pirovano
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lorenzi
authors.affiliation: IRCCS Centro Neurolesi "Bonino Pulejo", Via Palermo 113, 98121 Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy; Università Vita -Salute San Raffaele, Milan, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Smeraldi
authors.affiliation: San Raffaele Scientific Institute, Department of Clinical Neurosciences, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cavallaro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003024:Clozapine / Q000627:therapeutic use*; D003071:Cognition / Q000502:physiology; D015928:Cognitive Behavioral Therapy; D004298:Dopamine / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012559:Schizophrenia / Q000201:enzymology / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy*; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D002394:Catechol O-Methyltransferase; D003024:Clozapine; D004298:Dopamine
keywords: Catechol-O-methyltransferase; Clozapine; Cognitive remediation; Genetics; Schizophrenia