Effect of CACNA1C rs1006737 on neural correlates of verbal fluency in healthy individuals.
BACKGROUND
Recent genetic studies found the A allele of the variant rs1006737 in the alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene to be overrepresented in patients suffering from bipolar disorder, schizophrenia or major depression. While the functions underlying the pathophysiology of these psychiatric disorders are yet unknown, impaired performance in verbal fluency tasks is an often replicated finding. We investigated the influence of the rs1006737 single nucleotide polymorphism (SNP) on verbal fluency and its neural correlates.


METHODS
Brain activation was measured with functional magnetic resonance imaging (fMRI) during a semantic verbal fluency task in 63 healthy male individuals. They additionally performed more demanding verbal fluency tasks outside the scanner. All subjects were genotyped for CACNA1C rs1006737.


RESULTS
For the behavioral measures outside the scanner, rs1006737genotype had an effect on semantic but not on lexical verbal fluency with decreased performance in risk-allele carriers. In the fMRI experiment, while there were no differences in behavioural performance, increased activation in the left inferior frontal gyrus as well as the left precuneus was found in risk-allele carriers in the semantic verbal fluency task.


CONCLUSIONS
The rs1006737 variant does influence language production on a semantic level in conjunction with the underlying neural systems. These findings are in line with results of studies in bipolar disorder, schizophrenia and major depression and may explain some of the cognitive and brain activation variation found in these disorders.
Department of Psychiatry, Philipps-University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany. kruga@med.uni-marburg.de
Axel
A
Krug
Vanessa
V
Nieratschker
Valentin
V
Markov
Sören
S
Krach
Andreas
A
Jansen
Klaus
K
Zerres
Thomas
T
Eggermann
Tony
T
Stöcker
N Jon
NJ
Shah
Jens
J
Treutlein
Thomas W
TW
Mühleisen
Tilo
T
Kircher
D001921:Brain / Q000098:blood supply / Q000502:physiology*; D001931:Brain Mapping; D020746:Calcium Channels, L-Type / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007802:Language; D007807:Language Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013647:Task Performance and Analysis; D055815:Young Adult
C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D010100:Oxygen