Erik Smedler, MD, PhD; Christoph Abé, PhD; Erik Pålsson, PhD; Martin Ingvar, MD, PhD; Mikael Landén, MD, PhD
Background: The CACNA1C gene encodes the 1C subunit of L-type voltage-gated calcium channels and has been associated with several psychiatric syndromes — including bipolar disorder — in many genome-wide association studies. Experimental and clinical studies have reported changes with respect to behaviour and biomarkers in risk allele carriers, corroborating the essential role of the CACNA1C gene in neurons, during development and in the mature brain. However, the association of this gene with regional cortical thickness has not been evaluated in patients with bipolar disorder.
Methods: Using magnetic resonance imaging, we measured the average cortical thickness of 68 brain regions in 87 patients genotyped for the single-nucleotide polymorphism rs1006737 in CACNA1C.
Results: We found associations with the mean thickness of several cortical areas: the left lateral orbitofrontal and rostral anterior cingulate cortices, as well as other parts of the frontal and parietal cortices.
Limitations: This cross-sectional cohort study could not fully differentiate correlation from causation.
Conclusion: The CACNA1C polymorphism rs1006737 is associated with the mean thickness of cortical brain areas that have been shown to be altered in bipolar disorder.
Submitted Feb. 12, 2019; Revised Jul. 3, 2019; Accepted Aug. 1, 2019; Published online Dec. 12, 2019
Acknowledgments: The authors thank all those who kindly gave their time to participate in this research. The authors also thank the staff at the St. Göran bipolar affective disorder unit, including the study nurses.
Affiliations: From the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden (Smedler, Pålsson, Landén); the Department of Clinical Neuroscience, Osher Center for Integrative Medicine, Karolinska Institutet, Stockholm, Sweden (Abé, Ingvar); and the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden (Landén).
Funding: This research was supported by grants from the Swedish Research Council (2018-02653), the Swedish foundation for Strategic Research (KF10-0039), the Swedish Brain foundation, and the Swedish Federal Government under the LUA/ALF agreement (ALF 20170019, ALFGBG-716801). E. Smedler was funded by ALF Grants Västra Götalandsregionen. The funding sources were not involved in the analysis or interpretation of data or in writing the manuscript.
Competing interests: M. Landén has received lecture honoraria from Lundbeck Pharmaceuticals. No other competing interests were declared.
Contributors: All authors designed the study. C. Abé, E. Pålsson and M. Landén acquired the data, which E. Smelder, C. Abé and E. Pålsson analyzed. E. Smelder, C. Abé and M. Landén wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: E. Smedler, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden; email@example.com