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COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia.

ABSTRACT: 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.

SUBMITTER: Bosia M

PROVIDER: S-EPMC4346068 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia.

Bosia Marta M Bechi Margherita M Pirovano Adele A Buonocore Mariachiara M Lorenzi Cristina C Cocchi Federica F Bramanti Placido P Smeraldi Enrico E Cavallaro Roberto R

Health psychology and behavioral medicine 20140101 1

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, ...[more]

PMID: 25750798

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Project description:BackgroundLiterature explains participation limitations among people with schizophrenia through the context of metacognitive limitations, specifically in symptoms and in executive functions (EF). Research has shown mixed results regarding associations between symptoms and participation, reporting association with negative symptoms, positive symptoms, or only metacognitive limitations. The aim of this study was to deepen understanding of the symptoms' impact on the association between participation and executive function among people with schizophrenia.MethodsForty-three participants with schizophrenia received 8 group sessions of focused metacognitive intervention (MCG) aimed at promoting participation by focusing on EF components (e.g., analyzing individual cognitive strategy use). Three measures were administered: the Positive and Negative Syndrome Scale (PANSS) to evaluate symptoms, the Weekly Calendar Planning Assessment (WCPA) to assess EF, and the Activity Card Sort (ACS) to measure participation at the baseline and 12 weeks following completion of the intervention. Scores were compared to a matched control group of 41 people with schizophrenia who instead received treatment as usual. The role of PANSS as moderator was examined using multiple hierarchical regressions, entering interactions between the PANSS scores and WCPA change scores in the final regression step.ResultsRelationships were not significant for participants with high PANSS scores. A positive relationship existed between change in WCPA and change in ACS for participants with low PANSS scores.ConclusionsThese results demonstrate that low PANSS scores moderate the association between EF and participation and highlight the importance of symptoms as a predictor of participation following the MCG intervention.Trial registrationThe trial was retrospectively registered at clinical.Trialgov.Clinicaltrialsgov Identifier: NCT05556941. Clinicaltrial.gov registration date: 27/09/2022.

Project description:Catechol-O-methyl transferase (COMT) is a catabolic enzyme involved in the degradation of a number of bioactive molecules; of principal interest to psychiatry, these include dopamine. The enzyme is encoded by the COMT gene. COMT is located (along with 47 other genes) in a fragment of chromosome 22q11 which when deleted results in a complex syndrome, the psychiatric manifestations of which include schizophrenia and other psychoses. These 2 observations have placed COMT near the top of a rather long list of plausible candidate genes for schizophrenia. The ability to test the hypothesis that COMT might be a susceptibility gene for schizophrenia has been simplified in principle by the existence of a valine-to-methionine (Val/Met) polymorphism which results respectively in high and low activity forms of the enzyme. Given the unequivocal effect of this polymorphism on the function of COMT, and the evidence for a critical role for dopamine in the pathophysiology and treatment of psychosis, there are strong prior expectations that Val/Met influences susceptibility to schizophrenia as well as other psychiatric phenotypes. Indeed the Val/Met polymorphism has become the most widely studied polymorphism in psychiatry. In this review, we consider the evidence for and against the involvement of COMT in schizophrenia. The current data allow us to virtually exclude a simple relationship between schizophrenia and the Val/Met variant previously thought to dominate COMT function. However, recent data suggest a more complex pattern of genetic regulation of COMT function beyond that attributable to the Val/Met locus. Moreover, it is also clear that there is a complex nonlinear relationship between dopamine availability and brain function. These 2 factors, allied to phenotypic complexity within schizophrenia, make it difficult to draw strong conclusions regarding COMT in schizophrenia. Nevertheless, emerging research that takes greater account of all these levels of complexity is beginning to provide tantalizing, but far from definitive, support for the view that COMT influences susceptibility to at least some forms of psychosis.

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COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia.

Publications

COMT and 5-HT1A-receptor genotypes potentially affect executive functions improvement after cognitive remediation in schizophrenia.

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