title: The impact of a CACNA1C gene polymorphism on learning and hippocampal formation in healthy individuals: a diffusion tensor imaging study.
abstract: BACKGROUND
  Genome-wide association studies have identified the CACNA1C single nucleotide polymorphism (SNP) rs1006737 as one of the most consistent genetic findings as susceptibility locus for major psychiatric disorders. Furthermore, animal and genetic imaging studies have reported strong functional evidence for the association of CACNA1C with learning, memory, neural plasticity, and its association with the hippocampal formation. In the present study we investigated the impact of the CACNA1C SNP rs1006737 on the fractional anisotropy (FA) in the hippocampal formation as well as on verbal learning and memory in healthy individuals.
  
  
  METHODS
  118 healthy individuals (72 males, 46 females, age 18-56years) initially underwent diffusion tensor imaging (DTI), 100 of them were included in the final analysis. We used Tract-Based Spatial Statistics (TBSS) to examine the impact of the CACNA1C SNP rs1006737 on the hippocampal formation as predefined region of interest (ROI). Furthermore, all participants completed the Verbal Learning and Memory Test (VLMT).
  
  
  RESULTS
  In the VLMT genotype was significantly associated with learning performance. Bonferroni corrected post-hoc tests indicated a diminished performance at the beginning of the learning curve in risk allele carriers compared to non-risk allele carriers. The TBSS ROI analysis revealed one cluster of reduced FA in risk allele carriers compared to non-risk allele carriers located in the right hippocampal formation. Moreover, an association between the initial learning performance and FA values was found.
  
  
  CONCLUSIONS
  These findings demonstrate that genetic variation in the CACNA1C SNP rs1006737 is associated with FA reduction in the hippocampal formation as well as with differences in learning performance in healthy individuals.
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany. Electronic address: Dietsche@med.uni-marburg.de.
authors.forename: Bruno
authors.initials: B
authors.lastname: Dietsche
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
authors.forename: Heidelore
authors.initials: H
authors.lastname: Backes
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
authors.forename: Davide
authors.initials: D
authors.lastname: Laneri
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Weikert
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J 5, 68159 Mannheim, Germany.
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Witt
authors.affiliation: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J 5, 68159 Mannheim, Germany.
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Sommer
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Krug
mesh_terms: D000293:Adolescent; D000328:Adult; D020746:Calcium Channels, L-Type / Q000235:genetics*; D056324:Diffusion Tensor Imaging; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014706:Verbal Learning / Q000502:physiology*; D055815:Young Adult
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type
keywords: CACNA1C; Diffusion tensor imaging; Hippocampal formation; Learning; White matter