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CACNA1C Risk Variant and Mood Stabilizers Effects in the Prefrontal Cortical Thickness of Mexican Patients with Bipolar Disorder

Authors Rodríguez-Ramírez AM, Meza-Urzúa F, Cedillo-Ríos V, Becerra-Palars C, Jiménez-Pavón J, Morales-Cedillo IP, Sanabrais-Jiménez MA, Hernández-Muñoz S, Camarena-Medellín B

Received 14 January 2020

Accepted for publication 1 April 2020

Published 12 May 2020 Volume 2020:16 Pages 1199—1206

DOI https://doi.org/10.2147/NDT.S245911

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Roger Pinder


Alejandra Monserrat Rodríguez-Ramírez,1 Fátima Meza-Urzúa,2 Valente Cedillo-Ríos,3 Claudia Becerra-Palars,4 Joanna Jiménez-Pavón,4 Ingrid Pamela Morales-Cedillo,1 Marco Antonio Sanabrais-Jiménez,1 Sandra Hernández-Muñoz,1 Beatriz Camarena-Medellín1

1Departamento de Farmacogenética, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico; 2Kinder und Jugend Psychiatrie, Klinikum Idar-Oberstein, Idar-Oberstein, Germany; 3Departamento de Imágenes Cerebrales, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico; 4Dirección de Servicios Clínicos, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, Mexico

Correspondence: Beatriz Camarena-Medellín
Departamento de Farmacogenética, Instituto Nacional de Psiquiatria Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo, Huipulco, Mexico City CP 14370, Mexico
Tel +52 55 4160 5075
Fax +52 55 5513 3722
Email camare@imp.edu.mx

Purpose: Bipolar disorder (BD) is a condition associated with structural alterations in the prefrontal cortex (PFC); some genetic variants and mood stabilizer medications like lithium or valproate are associated with these changes. CACNA1C is a gene involved in BD pathology and brain function; carriers of the A allele of rs1006737 are reported to have increased risk for BD and increased cortical thickness (CT) in the PFC compared to non-carriers. Lithium is also associated with increased CT in the PFC of BD subjects compared to the ones on valproate. The influence of these treatments and gene variants over the PFC structure of Mexican subjects has not been explored. Therefore, we evaluate the effects of mood stabilizers and risk A allele of CACNA1C rs1006737 on the prefrontal cortical thickness of Mexican BD patients treated with lithium or valproate.
Patients and Methods: A cross-sectional study of 40 BD type I euthymic adult outpatients (20 treated with lithium and 20 with valproate) who underwent a 3T T1-weighted 3D brain scan and genotyping for CACNA1C risk allele rs1006737 was conducted. We performed a cortical thickness analysis of the dorsolateral and orbitofrontal regions of the prefrontal cortex with BrainVoyager 20.6. The effects of treatment and gene variants were analyzed with a two-way multivariate analysis of covariance.
Results: There was no association of CACNA1C risk allele rs1006737 with CT measures of both PFCs nor significant interaction between the genetic variant and treatment. Mood stabilizers reported the main effect on the CT measures of the right PFC of our sample. Patients on treatment with lithium showed higher mean CT on the right orbitofrontal cortex.
Conclusion: We did not find any association between the prefrontal CT and CACNA1C risk A allele rs1006737 in BD Mexican patients treated with lithium or valproate. Our results suggest that mood stabilizers had the main effect in the CT of the right PFC.

Keywords: genetics, mood disorders, neuroimaging

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