COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia.
Cognitive remediation therapy (CRT) has been proved to improve cognitive deficits in schizophrenia and to enhance functional outcomes of classical rehabilitation. However, CRT outcomes are heterogeneous and predictors of response are still unknown. Genetic variability, especially in the dopaminergic system, has been hypothesized to affect CRT. We previously reported that rs4680 of the catechol-O-methyltrasferase (COMT) influences improvements in executive functions in patients treated with CRT, but this result was not confirmed by other studies. Such inconsistent findings may depend, other than on clinical variables, also on other genes involved in cognition. Recent studies proved that serotonin 1A receptor (5-HT1A-R) regulates dopamine in the prefrontal cortex (PFC), and clinical works suggested a 5-HT1A-R role in cognition. We then analysed possible effects of COMT rs4680 and 5-HT1A-R rs6295 on CRT outcomes, taking into account also clinical and demographic factors. Eighty-six clinically stabilized schizophrenia patients treated with three months CRT were assessed with the Wisconsin Card Sorting Test, as a measure of executive functions, at enrolment and after CRT treatment, and underwent COMT and 5-HT1A-R genotyping. We found a significant main effect of COMT genotype and an interaction with 5-HT1A-R on executive function improvement after CRT. The results suggest that these two polymorphisms may have an additive effect on individual capacity to recover from cognitive deficit, probably through their role on PFC dopaminergic transmission modulation, known to be critical for modulating cognitive functions.
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy ; Center for Neurolinguistics and Theoretical Syntax, Institute for Advanced Study , Pavia , Italy.
Marta
M
Bosia
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy.
Margherita
M
Bechi
Faculty of Medicine and Surgery, Università Vita-Salute San Raffaele , Milan , Italy.
Adele
A
Pirovano
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy.
Mariachiara
M
Buonocore
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy.
Cristina
C
Lorenzi
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy.
Federica
F
Cocchi
IRCCS Centro Neurolesi "Bonino Pulejo" , Messina , Italy.
Placido
P
Bramanti
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy ; Faculty of Medicine and Surgery, Università Vita-Salute San Raffaele , Milan , Italy.
Enrico
E
Smeraldi
Clinical Neurosciences, San Raffaele Scientific Institute , Via Stamira d'Ancona 20, Milan 20127 Italy.
Roberto
R
Cavallaro
cognitive behaviour therapy; genomics; mental health and disorder; psychometrics; rehabilitation