Cognitive Remediation in Schizophrenia: Efficacy and Role of Neuroplasticity in "Top-down" and "Bottom-up" Mechanisms

Schizophrenia patients have deficits of different degrees in several cognitive domains, impacting their social functioning and quality of life. Cognitive remediation strategies are useful to treat cognitive deficits in patients with schizophrenia. There are at least two different cognitive remediation strategies: one has a "top-down" approach, and is aimed at higher-order cognitive processes, focusing on the training of executive functions. The other one has a "bottom-up" approach, aiming to first recovering the perceptual processing alterations that may affect performance in higher-order cognitive functions. This study addresses in parallel two research questions, one of clinical interest (Are both strategies effective in improving neurocognitive performance?) and another one focused on the psychological / neurobiological mechanisms of neurocognitive remediation (Which cognitive remediation strategies are related to changes in BDNF levels?). The specific objectives are: (1) Evaluate the effectiveness of two cognitive remediation strategies. (2) Study the critical moments of neuroplasticity for each cognitive remediation strategy, observing changes in BDNF levels at the end of the intervention and 12 weeks after the intervention. (3) Identify potential clinical and/or molecular predictors (BDNF levels or val66met polymorphism) of response for each cognitive remediation strategy. For these objectives, two randomized controlled trials with two arms will be carried out in parallel, one where patients will receive cognitive remediation and another consisting of a control group (with usual treatment). The control group subjects will remain on a waiting and observation list for 10 weeks, to later enter the active arm, which will also last 10 weeks. In one of the trials the active arm will consist of cognitive remediation therapy with a "bottom-up" approach (focused on perceptual training), while in the other trial the active arm will consist of cognitive remediation with a "top-down" approach (focused on executive skills training). Neurocognitive and clinical assessments will be carried out along with the measurement of BDNF levels at four evaluation times: one at baseline, one at the end of the observation period with treatment-as-usual, another at the end of cognitive remediation, and another after a 12 week follow-up period.