Bruno Dietsche1, Heidelore Backes2, Davide Laneri2, Thomas Weikert2, Stephanie H Witt3, Marcella Rietschel3, Jens Sommer2, Tilo Kircher2, Axel Krug2. 1. Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany. Electronic address: Dietsche@med.uni-marburg.de. 2. Department of Psychiatry and Psychotherapy, Philipps University Marburg, Rudolf-Bultmann-Str. 8, 35039 Marburg, Germany. 3. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J 5, 68159 Mannheim, Germany.
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. DISCUSSION: 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.
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. DISCUSSION: 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: Tilo Kircher; Markus Wöhr; Igor Nenadic; Rainer Schwarting; Gerhard Schratt; Judith Alferink; Carsten Culmsee; Holger Garn; Tim Hahn; Bertram Müller-Myhsok; Astrid Dempfle; Maik Hahmann; Andreas Jansen; Petra Pfefferle; Harald Renz; Marcella Rietschel; Stephanie H Witt; Markus Nöthen; Axel Krug; Udo Dannlowski Journal: Eur Arch Psychiatry Clin Neurosci Date: 2018-09-28 Impact factor: 5.270
Authors: Z D Kabir; A Che; D K Fischer; R C Rice; B K Rizzo; M Byrne; M J Glass; N V De Marco Garcia; A M Rajadhyaksha Journal: Mol Psychiatry Date: 2017-06-06 Impact factor: 15.992
Authors: Olav B Smeland; Oleksandr Frei; Karolina Kauppi; W David Hill; Wen Li; Yunpeng Wang; Florian Krull; Francesco Bettella; Jon A Eriksen; Aree Witoelar; Gail Davies; Chun C Fan; Wesley K Thompson; Max Lam; Todd Lencz; Chi-Hua Chen; Torill Ueland; Erik G Jönsson; Srdjan Djurovic; Ian J Deary; Anders M Dale; Ole A Andreassen Journal: JAMA Psychiatry Date: 2017-10-01 Impact factor: 21.596