Conditions: Schizophrenia
Keywords: Catecholamines Dopamine Clinical Trial fMRI PFC Vitamin B2 Riboflavin Tolcapone Placebo Normal Volunteers Schizophrenia Healthy Volunteers HV
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 210
Healthy volunteers: yes

Brief summary:
This study will evaluate whether Tolcapone improves cognition in healthy volunteers as well as patients with schizophrenia. Talcapone is a drug that has been FDA approved for Attention Deficit Disorder and allegedly increase the amount of the neurotransmitter dopamine in the frontal cortex of the brain.

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Detailed description:
Psychopharmacological modulation of the catecholaminergic system can enhance some aspects of cognitive function. For example, COMT inhibitors can slightly improve working memory/executive function. Differences in the response between individuals might be related to a number of factors, including variations in the genes. The recent finding that a polymorphism in the catechol-o-methyl-transferase (COMT) gene, which produces a 4 fold change in enzyme activity, accounts for 4 percent of the variance in performance of working memory tasks in humans suggest that COMT genotype may predict response to COMT inhibitors. In the present investigation our goal is to examine, in normal controls and patients with schizophrenia, the effect of a centrally acting (tolcapone) and of a peripherally acting (entacapone) COMT inhibitor on cognitive function. We predict that both normal controls and patients with schizophrenia with the val/val genotype will have a significant, though transient, improvement in working memory in subjects treated with tolcapone but not in those treated with entacapone. Furthermore, in conjunction with other NIMH imaging protocols, we would like to examine the neurophysiological correlates related to working memory. We predict, in tolcapone treated subjects, improved measures in prefrontal 'efficiency' in subjects and patients specifically with the val/val genotype. The present protocol will provide new insights on the importance of this genetic polymorphism in the regulation of aminergic-controlled cognitive function in normal individuals. Furthermore, this protocol will test whether COMT inhibitors offer a new treatment-based on genotype - for cognitive impairment in schizophrenia. No IND is required for the present study.

Arms:
arm 1: Placebo one week arm 2: Tolcapone one week

Interventions: intervention 1: Placebo intervention 2: Tolcapone
Intervention descriptions: intervention 1: Placebo: One capsule 3 times a day from Day 1 to Day 7 intervention 2: Tolcapone: One capsule 3 times a day from Day 1 to Day 7

Protocol document: