11.4 TOWARDS A MODEL FOR PERSONALIZING COGNITIVE REMEDIATION ON THE BASIS OF GENETIC POLYMORPHISMS

Abstract

Cognitive remediation (CR) for schizophrenia is an evidence-based intervention as it has been demonstrated in meta-analytic studies. However, little is known about how individual differences could be affecting responsiveness. Among other variables, genetic variability could help to understand some aspects of the underlying biological mechanisms of cognitive remediation in schizophrenia. Intuitively, genetic variability could be causing different responsivity to cognitive remediation and then, if that would be proved, variability in genetics could help to define new predictors of response and eventually they might allow us to personalize treatments in the near future. In this talk we will discuss the literature on genetic factors that may impact response to CR and the results of a systematic review will be presented. Moreover, an exploratory study testing the potential role of two different gene polymorphisms (COMT and BDNF gene) on cognition in a sample of n=110 participants with schizophrenia will be presented. Finally, a tentative model for predicting responsiveness to CR will be presented. Two different genes have been studied in the context of CR responsiveness. The brain-derived neurotrophic factor (BDNF) has been proposed as a specific marker of cognitive recovery. When samples were divided according to the resulting polymorphisms of the BDNF gene, the carriers of the Met allele behaved totally differently from the rest and no increase in serum BDNF levels was observed, while those without the Met allele did experience an increase in serum levels similar to previous studies. Those data could be potentially reflecting the presence of a negative response marker to cognitive remediation. On the other hand, some studies have shown that other gene polymorphisms, especially those that influence the release of dopamine, could act to influence the response to cognitive interventions in schizophrenia. The most studied is catechol-O-methyltransferase (COMT), which is an important enzyme for the degradation process of dopamine that regulates the availability of dopamine in the frontal cortex. Finally, in our own sample significant differences were found in different COMT polymorphisms in cognitive flexibility (t= 12.81; p = 0.001). In addition, significant differences were also found in measures of verbal learning (t= 11.87; p = 0.04) for different variants of the BDNF gene. Current data allow us to postulate a provisional model for predicting response to cognitive remediation including the BDNF Val66Met polymorphism and the COMT Val158Met polymorphisms. It seems like those polymorphisms could be accounting for different response to cognitive remediation in different cognitive domains: memory and cognitive flexibility. Eventually, if more new data about different genetic polymorphisms become available, we will able to enhance and improve that prediction model. The aforementioned model could contribute to the particularization and optimization of cognitive remediation interventions in schizophrenia.