Nimodipine improves cortical efficiency during working memory in healthy subjects

Area of Science:

• Neuroscience
• Pharmacology
• Genetics

Background:

• The CACNA1C gene, encoding the L-type calcium channel, is linked to schizophrenia risk.
• Individuals with the rs1006737 A allele show heightened frontal cortical activity during working memory.
• L-type calcium channel blockers are potential therapeutic agents for schizophrenia.

Purpose of the Study:

• To investigate the effects of the brain-penetrant calcium channel blocker nimodipine on brain activity.
• To examine nimodipine's impact on cognitive and emotional processes, particularly working memory.
• To assess if nimodipine's effects differ based on the rs1006737 genotype.

Main Methods:

• A double-blind, randomized, cross-over pharmaco-fMRI study in healthy men.
• Administration of a single 60mg dose of nimodipine or placebo.
• Participants were genotyped for the rs1006737 polymorphism.

Main Results:

• Nimodipine significantly decreased frontal (39.1%) and parietal (42.8%) cortical activity during the N-back task without affecting performance.
• Higher nimodipine concentrations correlated with greater reductions in frontal cortical activation.
• Carriers of the schizophrenia risk allele (A) exhibited a more substantial decrease in frontal activation.

Conclusions:

• Nimodipine reduces cortical activity during working memory, particularly in individuals with the schizophrenia risk genotype.
• This brain activity modulation may serve as a biomarker for L-type calcium channel blocker trials.
• Further research is warranted to explore nimodipine's efficacy in schizophrenia patients with the risk genotype.