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The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder

Molecular Psychiatry volume 16, pages 1070–1071 (2011)Cite this article

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Genome-wide association studies in bipolar disorder (BD)1 have implicated a single-nucleotide polymorphism (rs1006737, G → A) in the CACNA1C gene, which encodes for the alpha 1c (CAV1.2) subunit of the voltage-gated, L-type calcium channel. Neuroimaging studies of healthy individuals report that this risk allele modulates brain function within limbic (amygdala, anterior cingulate gyrus) and hippocampal regions during tasks of reward processing2, 3 and episodic memory.4 Moreover, animal studies suggest that the CaV1.2 L-type calcium channels influence emotional behaviour through enhanced neurotransmission via the lateral amygdala pathway.5 On the basis of this evidence, we tested the hypotheses that the CACNA1C rs1006737 risk allele will modulate neural responses within predefined prefrontal and subcortical regions of interest during emotional face processing and that this effect would be amplified in BD patients.

A total of 116 individuals of white British descent comprising 41 euthymic patients with BD, 25 of their first-degree relatives without any Axis I disorder and 50 healthy controls, were genotyped for the CACNA1C rs1006737 polymorphism (Table 1, Supplementary Material). These comprised 54 G homozygotes (BD patients: N=17; relatives: N=9; controls: N=28), 47 AG heterozygotes (BD patients: N=19; relatives: N=10; controls: N=18) and 15 A homozygotes (BD patients: N=5; relatives: N=6; controls: N=4), in Hardy-Weinberg equilibrium (P=0.92). Because of their small number AA individuals were considered together with AG heterozygotes within each diagnostic group (BD patients: N=24; relatives: N=16; controls: N=22) in further analyses. There was no effect of genotype or genotype by diagnosis interaction on demographic variables (P>0.15). Carriers of the CACNA1C rs1006737 risk allele had higher depressive and manic symptom scores (P=0.01) with this effect being more pronounced in patients (P<0.02) (Table 1, Supplementary Material).

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Author notes

  1. J Jogia and G Ruberto: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychosis studies, Section of Neurobiology of Psychosis, Institute of Psychiatry, King's College London, UK

    J Jogia, G Ruberto, G Lelli-Chiesa & S Frangou

  2. Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, UK

    E Vassos, M Maierú & D Collier

  3. Department of Psychiatry, Sant’ Andrea Hospital, Second Medical School, La Sapienza University, Italy

    G Ruberto, G Lelli-Chiesa, R Tatarelli & P Girardi

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  1. J Jogia
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  2. G Ruberto
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  3. G Lelli-Chiesa
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  4. E Vassos
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  5. M Maierú
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  9. S Frangou
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Correspondence to S Frangou.

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Jogia, J., Ruberto, G., Lelli-Chiesa, G. et al. The impact of the CACNA1C gene polymorphism on frontolimbic function in bipolar disorder. Mol Psychiatry 16, 1070–1071 (2011). https://doi.org/10.1038/mp.2011.49

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