Scotti-Muzzi Estêvão, Chile Thais, Vallada Homero, Otaduy Maria Concepción Garcia, Soeiro-de-Souza Márcio Gerhardt
Department 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.
Genetics and Pharmacogenetics Unit (PROGENE), Institute of Psychiatry, School of Medicine, University of São Paulo (IPq-FMUSP), Brazil.
Eur Neuropsychopharmacol. 2022 Jun;59:26-35. doi: 10.1016/j.euroneuro.2022.04.001. Epub 2022 May 8.
Abnormalities in Ca 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 (H-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 Ca. Thus, this study aimed to explore the association of the CACNA1C genotype with ACC glutamatergic metabolites measured by H-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 H-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 Ca overload and excitotoxicity.
双相情感障碍（BD）中钙稳态异常与谷氨酸能受体和电压门控钙通道功能受损有关。通过质子磁共振波谱（H-MRS）在BD患者中持续发现前扣带回皮质（ACC）谷氨酸能神经代谢物增加。编码L型钙通道α1-C亚基的CACNA1C基因（rs1006737）中的单核苷酸多态性（SNP）与BD相关，据报道可调节细胞内钙。因此，本研究旨在探讨BD患者和健康对照（HC）中CACNA1C基因型与通过H-MRS测量的ACC谷氨酸能代谢物之间的关联。对总共194名受试者（121名I型双相情感障碍缓解期患者和73名健康对照（HC））进行了CACNA1C rs1006737基因分型，接受了3特斯拉H-MRS成像检查，并评估了ACC谷氨酸能代谢物。我们发现BD患者中AA携带者的谷氨酸能代谢物总体增加。具体而言，在总体样本（BD + HC）中，与AG和GG基因型相比，AA基因型受试者的Glx/Cr更高。此外，BD组中AA基因型的女性个体的Glx/Cr高于其他基因型个体。使用抗惊厥药物的CACNA1C AA携带者的谷氨酰胺（Glx-Glu）估计值高于其他基因型。因此，本研究表明钙通道遗传学与BD中谷氨酸能代谢物增加之间存在关联，可能在细胞内钙超载和兴奋性毒性中起协同作用。
