CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls

Martin Tesli (Lead / Corresponding author), Kristina C. Skatun, Olga Therese Ousdal, Andrew Anand Brown, Christian Thoresen, Ingrid Agartz, Ingrid Melle, Srdjan Djurovic, Jimmy Jensen, Ole A Andreassen

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Objectives: Several genetic studies have implicated the CACNA1C SNP rs1006737 in bipolar disorder (BD) and schizophrenia (SZ) pathology. This polymorphism was recently found associated with increased amygdala activity in healthy controls and patients with BD. We performed a functional Magnetic Resonance Imaging (fMRI) study in a sample of BD and SZ cases and healthy controls to test for altered amygdala activity in carriers of the rs1006737 risk allele (AA/AG), and to investigate if there were differences across the diagnostic groups.

Methods: Rs1006737 was genotyped in 250 individuals (N = 66 BD, 61 SZ and 123 healthy controls), all of Northern European origin, who underwent an fMRI negative faces matching task. Statistical tests were performed with a model correcting for sex, age, diagnostic category and medication status in the total sample, and then in each diagnostic group.

Results: In the total sample, carriers of the risk allele had increased activation in the left amygdala. Group-wise analyses showed that this effect was significant in the BD group, but not in the other diagnostic groups. However, there was no significant interaction effect for the risk allele between BD and the other groups.

Conclusions: These results indicate that CACNA1C SNP rs1006737 affects amygdala activity during emotional processing across all diagnostic groups. The current findings add to the growing body of knowledge of the pleiotropic effect of this polymorphism, and further support that ion channel dysregulation is involved in the underlying mechanisms of BD and SZ.

Original languageEnglish
Pages (from-to)e56970
Number of pages6
JournalPLoS ONE
Volume8
Issue number2
DOIs
Publication statusPublished - 3 Nov 2013

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amygdala
Amygdala
Bipolar Disorder
Schizophrenia
Polymorphism
alleles
magnetic resonance imaging
Statistical tests
genetic polymorphism
Pathology
Ion Channels
Alleles
ion channels
Single Nucleotide Polymorphism
Chemical activation
sampling
drug therapy
Magnetic Resonance Imaging
statistical analysis
Processing

Keywords

  • Alleles
  • Amygdala/pathology
  • Bipolar Disorder/diagnosis
  • Calcium Channels, L-Type/genetics
  • Humans
  • Magnetic Resonance Imaging
  • Polymorphism, Single Nucleotide
  • Psychomotor Performance
  • Reaction Time
  • Schizophrenia/diagnosis

Cite this

Tesli, M., Skatun, K. C., Ousdal, O. T., Brown, A. A., Thoresen, C., Agartz, I., ... Andreassen, O. A. (2013). CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls. PLoS ONE, 8(2), e56970. https://doi.org/10.1371/journal.pone.0056970
Tesli, Martin ; Skatun, Kristina C. ; Ousdal, Olga Therese ; Brown, Andrew Anand ; Thoresen, Christian ; Agartz, Ingrid ; Melle, Ingrid ; Djurovic, Srdjan ; Jensen, Jimmy ; Andreassen, Ole A. / CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls. In: PLoS ONE. 2013 ; Vol. 8, No. 2. pp. e56970.
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Tesli, M, Skatun, KC, Ousdal, OT, Brown, AA, Thoresen, C, Agartz, I, Melle, I, Djurovic, S, Jensen, J & Andreassen, OA 2013, 'CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls', PLoS ONE, vol. 8, no. 2, pp. e56970. https://doi.org/10.1371/journal.pone.0056970

CACNA1C risk variant and amygdala activity in bipolar disorder, schizophrenia and healthy controls. / Tesli, Martin (Lead / Corresponding author); Skatun, Kristina C.; Ousdal, Olga Therese; Brown, Andrew Anand; Thoresen, Christian; Agartz, Ingrid; Melle, Ingrid; Djurovic, Srdjan; Jensen, Jimmy; Andreassen, Ole A.

In: PLoS ONE, Vol. 8, No. 2, 03.11.2013, p. e56970.

Research output: Contribution to journalArticle

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AU - Tesli, Martin

AU - Skatun, Kristina C.

AU - Ousdal, Olga Therese

AU - Brown, Andrew Anand

AU - Thoresen, Christian

AU - Agartz, Ingrid

AU - Melle, Ingrid

AU - Djurovic, Srdjan

AU - Jensen, Jimmy

AU - Andreassen, Ole A

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Y1 - 2013/11/3

N2 - Objectives: Several genetic studies have implicated the CACNA1C SNP rs1006737 in bipolar disorder (BD) and schizophrenia (SZ) pathology. This polymorphism was recently found associated with increased amygdala activity in healthy controls and patients with BD. We performed a functional Magnetic Resonance Imaging (fMRI) study in a sample of BD and SZ cases and healthy controls to test for altered amygdala activity in carriers of the rs1006737 risk allele (AA/AG), and to investigate if there were differences across the diagnostic groups.Methods: Rs1006737 was genotyped in 250 individuals (N = 66 BD, 61 SZ and 123 healthy controls), all of Northern European origin, who underwent an fMRI negative faces matching task. Statistical tests were performed with a model correcting for sex, age, diagnostic category and medication status in the total sample, and then in each diagnostic group.Results: In the total sample, carriers of the risk allele had increased activation in the left amygdala. Group-wise analyses showed that this effect was significant in the BD group, but not in the other diagnostic groups. However, there was no significant interaction effect for the risk allele between BD and the other groups.Conclusions: These results indicate that CACNA1C SNP rs1006737 affects amygdala activity during emotional processing across all diagnostic groups. The current findings add to the growing body of knowledge of the pleiotropic effect of this polymorphism, and further support that ion channel dysregulation is involved in the underlying mechanisms of BD and SZ.

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KW - Calcium Channels, L-Type/genetics

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KW - Polymorphism, Single Nucleotide

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