title: A genome-wide supported variant in CACNA1C influences hippocampal activation during episodic memory encoding and retrieval.
abstract: The alpha 1C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene is one of the best replicated susceptibility loci for bipolar disorder, schizophrenia and major depression. It is involved in learning, memory and brain plasticity. Genetic studies using functional magnetic resonance imaging (fMRI) reported evidence of association with the CACNA1C single nucleotide polymorphism rs1006737 with functional correlates of episodic memory encoding and retrieval, especially activations in the hippocampus. These results, however, are inconsistent with regard to the magnitude and directionality of effect. In the present study, brain activation was measured with fMRI during an episodic memory encoding and retrieval task using neutral faces in two independent samples of 94 and 111 healthy subjects, respectively. Within whole brain analyses, a main effect of genotype emerged mainly in the right hippocampus during encoding as well as retrieval within the first sample: Carriers of the minor allele (A) exhibited lower activations compared to G/G allele carriers. This effect could be replicated within the second sample, however, only for the retrieval condition. The results strengthen findings that rs1006737 is associated with neural systems related to memory processes in hippocampal regions which are detectable in healthy subjects.
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Street 8, 35039, Marburg, Germany, kruga@med.uni-marburg.de.
authors.forename: Axel
authors.initials: A
authors.lastname: Krug
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.forename: Heidelore
authors.initials: H
authors.lastname: Backes
authors.forename: Bruno
authors.initials: B
authors.lastname: Dietsche
authors.forename: Vanessa
authors.initials: V
authors.lastname: Nieratschker
authors.forename: N Jon
authors.initials: NJ
authors.lastname: Shah
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D020746:Calcium Channels, L-Type / Q000235:genetics*; D004192:Discrimination, Psychological; D017352:Echo-Planar Imaging; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006624:Hippocampus / Q000098:blood supply / Q000502:physiology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D061212:Memory, Episodic; D011939:Mental Recall / Q000502:physiology*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D055815:Young Adult
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D010100:Oxygen