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Updated: Sep 23, 2025

Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Association between CACNA1C gene rs100737 polymorphism and glutamatergic neurometabolites in bipolar disorder
Estêvão Scotti-Muzzi1, Thais Chile2, Homero Vallada2
1Department of Psychiatry, University of São Paulo (FMUSP), Institute of Psychiatry, CEAPESQ, PROGRUDA, School of Medicine, Dr. Ovidio Pires de Campos s / n. Clinic Hospital, São Paulo 05403-010, Brazil.
Abstract:
Abnormalities in Ca2+ homeostasis in Bipolar Disorders (BD) have been associated with impairments in glutamatergic receptors and voltage-gated calcium channels. Increased anterior cingulate cortex (ACC) glutamatergic neurometabolites have been consistently disclosed in BD by proton magnetic resonance spectroscopy (1H-MRS). A single nucleotide polymorphism (SNP) in the CACNA1C gene (rs1006737), which encodes the alpha 1-C subunit of the L-type calcium channel, has been associated with BD and is reported to modulate intra-cellular Ca2+. Thus, this study aimed to explore the association of the CACNA1C genotype with ACC glutamatergic metabolites measured by 1H-MRS in both BD and HC subjects. A total of 194 subjects (121 euthymic BD type I patients and 73 healthy controls (HC) were genotyped for CACNA1C rs1006737, underwent a 3-Tesla 1H-MRS imaging examination and ACC glutamatergic metabolite were assessed. We found overall increased glutamatergic metabolites in AA carriers in BD. Specifically, higher Glx/Cr was observed in subjects with the AA genotype compared to both AG and GG in the overall sample (BD + HC). Also, female individuals in the BD group with AA genotype were found to have higher Glx/Cr compared to those with other genotypes. CACNA1C AA carriers in use of anticonvulsant medication had higher estimated Glutamine (Glx-Glu) than the other genotypes. Thus, this study suggest an association between calcium channel genetics and increased glutamatergic metabolites in BD, possibly playing a synergic role in intracellular Ca2+ overload and excitotoxicity.
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