Exercise Induced Neuroplasticity to Enhance Therapeutic Outcomes of Cognitive Remediation in Schizophrenia: Analyzing the Role of Brai nderived Neurotrophic Factor.

Abstract

Cognitive impairment is a major manifestation of schizophrenia and a crucial treatment target as these deficits are closely related to patients' functional outcomes. Cognitive remediation is the gold-standard practice to address cognitive deficits in schizophrenia. There is clear evidence stating that cognitive remediation improves cognitive function and promotes structural neuroplastic changes in patients with schizophrenia, with brain-derived neurotrophic factor (BDNF) expression emerging as a potential biomarker for its efficacy. This is particularly important as there is clear evidence relating atypical BDNF expression to cognitive impairment in patients with schizophrenia. Despite the valuable role of cognitive remediation in the management of schizophrenia, there is still a need to develop methods that allow maximizing its efficacy. In this review, we present a hypothesis arguing that cognitive remediation efficacy for patients with schizophrenia can be enhanced by aerobic exercise-induced BDNF upregulation. There have been a few trials reporting that combining aerobic exercise with cognitive training was superior to cognitive training alone to improve cognitive functioning in patients with schizophrenia. Furthermore, there is preliminary evidence suggesting that combined aerobic and cognitive training can increase peripheral BDNF levels. Thereby, engaging in aerobic exercise in close temporal proximity to cognitive remediation may allow achieving a state of neuroplastic readiness in the brain, facilitating cognitive functioning enhancement. Although this hypothesis still lacks evidence, future clinical trials using cognitive remediation for schizophrenia should explore strategies to maximize neuroplasticity and achieve optimal cognitive improvements.