This study aims to evaluate the acute effects of nimodipine on cognitive performance in patients with schizophrenia using a battery of cognitive assessments.The subjects will also complete a 30-minute structural and functional MRI scan, with the goal of linking brain activity with working memory performance. Investigators predict that the performance increase induced by nimodipine will be greater in subjects who carry the A allele for the Calcium Voltage-Gated Channel Subunit Alpha1 C (CACNA1C) risk single nucleotide polymorphism (SNP) (rs1006737) in comparison to the response of G carriers.
The main cognitive task of interest in this study is the N-back task because of the observed attenuation of prefrontal and parietal cortical activity after nimodipine administration in healthy subjects. Investigators hypothesize that acute nimodipine administration will improve cortical activation, which will lead to improved cognitive performance. The current study will provide insight whether nimodipine or another calcium channel blocker could be used as a treatment approach to alleviate cognitive deficits in patients with schizophrenia.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
QUADRUPLE
Enrollment
18
Subject will receive two 30mg capsules of nimodipine during study visit.
Two coconut oil capsules that mimic the size and color of the nimodipine capsules
Johns Hopkins Bayview Medical Center
Baltimore, Maryland, United States
Johns Hopkins University
Baltimore, Maryland, United States
Brain activity as assessed by BOLD fMRI
participants will complete an MRI scan to link brain activity with cognitive performance. Measures will be recorded in Arbitrary units.
Time frame: between 30 min and 1 hour after dose
Changes in Visual Learning and Memory Score
Participants will complete the Brief Visuospatial Memory Task - Revised (BVMT-R) before and after administration of drug or placebo to determine the effect of nimodipine on visuospatial memory in patients with schizophrenia. Scores range from 0 to 60, with higher values indicating better performance. Administration takes approximately 45 minutes to complete (including a 25 minute delay)
Time frame: approximately an hour after dose
Changes in Auditory Learning and Memory Score
During each study visit, participants will complete the Hopkins Verbal Learning Task - Revised (HVLT-R) before and after administration of drug or placebo to determine the effect of nimodipine on verbal learning and memory in patients with schizophrenia. Scores range from 0 to 60, with higher values indicating better performance. Administration takes approximately 35 minutes to complete (including a 20-25 minute delay).
Time frame: approximately an hour after dose
Changes in Global Neurocognitive effect as assessed by the Global Neurocognitive Assessment (GNA)
During each study visit, participants will complete the Global Neurocognitive Assessment (GNA) before and after administration of drug or placebo to determine the effect of nimodipine on a range of neurocognitive measures in patients with schizophrenia. The GNA contains 10 items with varying score ranges. Higher scores indicate better performance.
Time frame: approximately an hour after dose
Effect of CACNA1C genotype on cognitive performance measures
The CACNA1C risk-associated SNP (rs1006737) will be tested using a linear regression (with copy of A alleles) with each cognitive domain score to determine if CACNA1C genetics impact response to nimodipine.
Time frame: during 2-3 hour study visit
Broader genetic associations with cognitive performance
Genetic data will be used more broadly to include testing of the effects of genetic variation including but not limited to schizophrenia, cognition, behavior, and drug metabolism.
Time frame: during 2-3 hour study visit
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