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Initial evidence for the role of CACNA1C on subcortical brain morphology in patients with bipolar disorder

Published online by Cambridge University Press:  16 April 2020

E. Perrier
Affiliation:
Medizinische Fakultät, Universität zu Köln, Germany Section of Neurobiology of Psychosis, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
F. Pompei
Affiliation:
Section of Neurobiology of Psychosis, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
G. Ruberto
Affiliation:
Section of Neurobiology of Psychosis, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
E. Vassos
Affiliation:
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
D. Collier
Affiliation:
Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK
S. Frangou*
Affiliation:
Section of Neurobiology of Psychosis, Department of Psychosis Studies, Institute of Psychiatry, King's College London, UK
*
*Corresponding author. Tel.: +44 207 8480425. E-mail address: [email protected] (S. Frangou).
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Abstract

Background

The polymorphism rs1006737 within the CACNA1C gene is associated with increased risk for bipolar disorder (BD) and variations in brain morphology and function of subcortical regions. Here we sought to investigate the influence of CACNA1C polymorphism on key subcortical brain structures implicated in the pathophysiology of BD.

Methods

Structural magnetic resonance imaging scans were acquired from 41 euthymic patients with BD and 40 healthy controls, who were also genotyped for the CACNA1C rs1006737 polymorphism. The effect of diagnosis, genotype and their interaction was examined in predefined volumes of interest in the basal ganglia, hypothalamus and amygdala extracted using SPM5.

Results

Carriers of the CACNA1C rs1006737 risk allele showed increased grey matter density in the right amygdala and right hypothalamus irrespective of diagnosis. An interaction between genotype and diagnosis was observed in the left putamen which was smaller in BD patients carrying the risk allele than in healthy controls.

Conclusions:

The CACNA1C rs1006737 polymorphism influences anatomical variation within subcortical regions involved in emotional processing.

Type
Short communication
Copyright
Copyright © Elsevier Masson SAS 2011

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References

Bigos, KL, Mattay, VS, Callicott, JH, Straub, RE, Vakkalanka, R, Kolachana, B, et al.Genetic variation in CACNA1C affects brain circuitries related to mental illness. Arch Gen Psychiatry 2010; 67: 939945.CrossRefGoogle ScholarPubMed
Cerullo, MA, Adler, CM, Delbello, MP, Strakowski, SMThe functional neuroanatomy of bipolar disorder. Int Rev Psychiatry 2009; 21: 314322.CrossRefGoogle ScholarPubMed
Erk, S, Meyer-Lindenberg, A, Schnell, K, Opitz von Boberfeld, C, Esslinger, C, Kirsch, P, et al.Brain function in carriers of a genome-wide supported bipolar disorder variant. Arch Gen Psychiatry 2010; 67: 803811.CrossRefGoogle ScholarPubMed
Ferreira, MA, O’Donovan, MC, Meng, YA, Jones, IR, Ruderfer, DM, Jones, L, et al.Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder. Nat Genet 2008; 40: 10561058.CrossRefGoogle ScholarPubMed
Franke, B, Vasquez, AA, Veltman, JA, Brunner, HG, Rijpkema, M, Fernández, GGenetic variation in CACNA1C, a gene associated with bipolar disorder, influences brainstem rather than gray matter volume in healthy individuals. Biol Psychiatry 2010; 68: 586588.CrossRefGoogle ScholarPubMed
Green, EK, Grozeva, D, Jones, I, Jones, L, Kirov, G, Caesar, S, et al.The bipolar disorder risk allele at CACNA1C also confers risk of recurrent major depression and of schizophrenia. Mol Psychiatry 2009 49 doi:10.1038/mp.2009Google ScholarPubMed
Hwang, J, Lyoo, IK, Dager, SR, Friedman, SD, Oh, JS, Lee, JY, et al.Basal ganglia shape alterations in bipolar disorder. Am J Psychiatry 2006; 163: 276285.CrossRefGoogle ScholarPubMed
Kempton, MJ, Geddes, JR, Ettinger, U, Williams, SCR, Grasby, PMMeta-analysis, database, and meta-regression of 98 structural imaging studies in bipolar disorder. Arch Gen Psychiatry 2008; 65: 10171032.CrossRefGoogle ScholarPubMed
Kempton, MJ, Ruberto, G, Vassos, E, Tatarelli, R, Girardi, P, Collier, D, et al.Effects of the CACNA1C risk allele for bipolar disorder on cerebral gray matter volume in healthy individuals. Am J Psychiatry 2009; 166: 14131414.CrossRefGoogle ScholarPubMed
Moosmang, S, Haider, N, Klugbauer, N, Adelsberger, H, Langwieser, N, Müller, J, et al.Role of hippocampal Cav1.2 Ca2 channels in NMDA receptor-independent synaptic plasticity and spatial memory. J Neurosci 2005; 25: 98839892.CrossRefGoogle ScholarPubMed
Pariante, CM, Vassilopoulou, K, Velakoulis, D, Phillips, L, Soulsby, B, Wood, SJ, et al.Pituitary volume in psychosis. Br J Psychiatry 2004; 185: 510.CrossRefGoogle ScholarPubMed
Shinnick-Gallagher, P, McKernan, MG, Xie, J, Zinebi, FL-type voltage-gated calcium channels are involved in the in vivo and in vitro expression of fear conditioning. Ann N Y Acad Sci 2003; 985: 135149.CrossRefGoogle ScholarPubMed
Sinnegger-Brauns, MJ, Hetzenauer, A, Huber, IG, Renström, E, Wietzorrek, G, Berjukov, S, et al.Isoform-specific regulation of mood behavior and pancreatic β cell and cardiovascular function by L-type Ca2+ channels. J Clin Invest 113 2004 1430CrossRefGoogle Scholar
Takahashi, T, Walterfang, M, Wood, SJ, Kempton, MJ, Jogia, J, Lorenzetti, V, et al.Pituitary volume in patients with bipolar disorder and their first-degree relatives. J Affect Disord 2010; 24: 256261.CrossRefGoogle Scholar
Wessa, M, Linke, J, Witt, SH, Nieratschker, V, Esslinger, C, Kirsch, P, et al.The CACNA1C risk variant for bipolar disorder influences limbic activity. Mol Psychiatry 2010 103 doi:10.1038/mp.2009Google ScholarPubMed
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