Cognitive remediation in schizophrenia: efficacy and role of neuroplasticity in “top-down” and “bottom-up” mechanisms—a randomized, double-blind, treatment-as-usual-controlled study protocol
- 1Clínica Psiquiátrica Universitaria, Hospital Clínico de la Universidad de Chile, Universidad de Chile , ,
Abstract
Objectives: Schizophrenia is characterized by positive, negative and cognitive symptoms, including different degrees of impairment in several neurocognitive domains, such as executive function, processing speed, learning and memory, which impact a patient´s functioning and quality of life. Cognitive remediation can help restore cognitive functioning through repeated exercises, following at least two possible strategies: a “top-down” approach, focused on training executive functions, or perceptual training, a “bottom-up” approach, aimed at first addressing impairments in perceptual processing. This study aims to clarify whether both approaches have comparable efficacy in improving neurocognitive performance, and to explore the timing of their cognitive and molecular effects. It will also examine the relationship between these approaches and changes in BDNF levels, considered a biomarker of neuroplasticity.
Materials and methods: In order to have a control group, patients will undergo an initial 10-week observation period receiving treatment as usual, followed by randomization into either executive training or perceptual training during the active phase of the trial. Clinical and neurocognitive assessments, as well as blood sampling, will be conducted at the beginning and end of each stage. Finally, assessments will be repeated after a 12-week follow-up period.
Discussion: The study aims to answer these research questions concerning clinical efficacy and molecular mechanisms and expects to identify possible clinical or molecular biomarkers (such as BDNF levels or the Val66Met polymorphism) that could be helpful as predictors of neurocognitive treatment response for each remediation strategy, thereby contributing to a personalized treatment approach. Study registered on clinicaltrials.gov number NCT06482918.
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BibTeX
@article{cifuentes2026cognitive,
title = {{Cognitive remediation in schizophrenia: efficacy and role of neuroplasticity in “top-down” and “bottom-up” mechanisms—a randomized, double-blind, treatment-as-usual-controlled study protocol}},
author = {Juan I. Cifuentes and Constanza Orellana and Diego Tello and Cristian Ramírez and Catalina Prieto and Jessica M. Guasti and Rodrigo R. Nieto},
journal = {Frontiers in psychiatry},
year = {2026},
month = oct,
doi = {10.3389/fpsyt.2026.1936475},
url = {https://europepmc.org/article/PMC/PMC13691481},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cognitive remediation in schizophrenia: efficacy and role of neuroplasticity in “top-down” and “bottom-up” mechanisms—a randomized, double-blind, treatment-as-usual-controlled study protocol
AU - Juan I. Cifuentes
AU - Constanza Orellana
AU - Diego Tello
AU - Cristian Ramírez
AU - Catalina Prieto
AU - Jessica M. Guasti
AU - Rodrigo R. Nieto
PY - 2026
DA - 2026/10/09
JO - Frontiers in psychiatry
DO - 10.3389/fpsyt.2026.1936475
UR - https://europepmc.org/article/PMC/PMC13691481
AB - Objectives: Schizophrenia is characterized by positive, negative and cognitive symptoms, including different degrees of impairment in several neurocognitive domains, such as executive function, processing speed, learning and memory, which impact a patient´s functioning and quality of life. Cognitive remediation can help restore cognitive functioning through repeated exercises, following at least two possible strategies: a “top-down” approach, focused on training executive functions, or perceptual training, a “bottom-up” approach, aimed at first addressing impairments in perceptual processing. This study aims to clarify whether both approaches have comparable efficacy in improving neurocognitive performance, and to explore the timing of their cognitive and molecular effects. It will also examine the relationship between these approaches and changes in BDNF levels, considered a biomarker of neuroplasticity. Materials and methods: In order to have a control group, patients will undergo an initial 10-week observation period receiving treatment as usual, followed by randomization into either executive training or perceptual training during the active phase of the trial. Clinical and neurocognitive assessments, as well as blood sampling, will be conducted at the beginning and end of each stage. Finally, assessments will be repeated after a 12-week follow-up period. Discussion: The study aims to answer these research questions concerning clinical efficacy and molecular mechanisms and expects to identify possible clinical or molecular biomarkers (such as BDNF levels or the Val66Met polymorphism) that could be helpful as predictors of neurocognitive treatment response for each remediation strategy, thereby contributing to a personalized treatment approach. Study registered on clinicaltrials.gov number NCT06482918.
SN - 1664-0640
ER -