Evaluation of the Efficacy of Tolcapone as a Genotype-based Targeted Cognitive Enhancer in Schizophrenia, Based on the Polymorphism rs4680
Objective: To assess the efficacy of tolcapone to improve cognition in schizophrenia, as a genotype-based targeted treatment of cognitive and negative symptoms of schizophrenia considering the polymorphism rs4680. Methodology: 20 patients with chronic and stabilized schizophrenia (10 patients with genotype Val/Val and 10 patients with genotype Met/Met according to polymorphism rs4680) will receive treatment with tolcapone during 7 days. The cognitive function and clinical status will be evaluated with a neuropsychological battery and appropriate clinical scales before and after treatment. The efficiency of the activation of the prefrontal cortex will be measured using functional magnetic resonance imaging (fMRI) before and after treatment. Hypothesis: Only patients with genotype Val/Val treated with tolcapone would show a cognitive improvement, a higher efficiency of the activation of the prefrontal cortex and an amelioration of some negative symptoms.
• Ability to give informed consent and express the wish to fulfill all the requirements of the protocol during the study period.
• The patient must be capable of fulfillment of all the requirements of the clinical trial, at the investigator's discretion.
• Patients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Only chronic patients will be recruited, and they must be clinically compensated in order to consent to participate. The determination of clinical compensation will be conducted according with these criteria: i) outpatients, with absence of hospitalization due to acute psychiatric decompensation in the previous year, and ii) maintained GAF score equal or higher than 60 during the previous month. The recruitment process will include a clinical interview to verify the diagnosis.
• Caucasic ethnicity
• Negative pregnancy test for women of childbearing age.