Nimodipine improves cortical efficiency during working memory in healthy subjects
| Autor: | Caroline F. Zink, Jay J. Pillai, Eric Zimmerman, Daniel R. Weinberger, Mellissa Giegerich, Greer E. Prettyman, Molly Patricia O’Rourke, Marcus van Ginkel, Pamela Hummert, Jennifer C. Breakey, Kayla E. Carta, Edward J. Fuchs, Eesha Singh, Mark A. Marzinke, Craig W. Hendrix, Kristin L. Bigos |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Brain activity and meditation medicine.drug_class Prefrontal Cortex Calcium channel blocker Predictive markers Placebo Article lcsh:RC321-571 Cellular and Molecular Neuroscience Internal medicine Humans Medicine Prefrontal cortex lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Nimodipine Biological Psychiatry business.industry Working memory Calcium channel Medical genetics Calcium Channel Blockers medicine.disease Healthy Volunteers Psychiatry and Mental health Memory Short-Term Endocrinology Schizophrenia Clinical pharmacology business medicine.drug |
| Zdroj: | Translational Psychiatry, Vol 10, Iss 1, Pp 1-8 (2020) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | The L-type calcium channel gene, CACNA1C, is a validated risk gene for schizophrenia and the target of calcium channel blockers. Carriers of the risk-associated genotype (rs1006737 A allele) have increased frontal cortical activity during working memory and higher CACNA1C mRNA expression in the prefrontal cortex. The aim of this study was to determine how the brain-penetrant calcium channel blocker, nimodipine, changes brain activity during working memory and other cognitive and emotional processes. We conducted a double-blind randomized cross-over pharmacoMRI study of a single 60 mg dose of oral nimodipine solution and matching placebo in healthy men, prospectively genotyped for rs1006737. With performance unchanged, nimodipine significantly decreased frontal cortical activity by 39.1% and parietal cortical activity by 42.8% during the N-back task (2-back > 0-back contrast; PFWE n = 28). Higher peripheral nimodipine concentrations were correlated with a greater decrease in activation in the frontal cortex. Carriers of the risk-associated allele, A (n = 14), had a greater decrease in frontal cortical activation during working memory compared to non-risk allele carriers. No differences in brain activation were found between nimodipine and placebo for other tasks. Future studies should be conducted to test if the decreased cortical brain activity after nimodipine is associated with improved working memory performance in patients with schizophrenia, particularly those who carry the risk-associated genotype. Furthermore, changes in cortical activity during working memory may be a useful biomarker in future trials of L-type calcium channel blockers. |
| Databáze: | OpenAIRE |
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