title: DNA hypomethylation of Synapsin II CpG islands associates with increased gene expression in bipolar disorder and major depression.
abstract: The Synapsins (SYN1, SYN2, and SYN3) are important players in the adult brain, given their involvement in synaptic transmission and plasticity, as well as in the developing brain through roles in axon outgrowth and synaptogenesis. We and others previously reported gene expression dysregulation, both as increases and decreases, of Synapsins in mood disorders, but little is known about the regulatory mechanisms leading to these differences. Thus, we proposed to study DNA methylation at theses genes' promoter regions, under the assumption that altered epigenetic marks at key regulatory sites would be the cause of gene expression changes and thus part of the mood disorder etiology.
  
  
  
  We performed CpG methylation mapping focusing on the three genes' predicted CpG islands using the Sequenom EpiTYPER platform. DNA extracted from post-mortem brain tissue (BA10) from individuals who had lived with bipolar disorder (BD), major depressive disorder (MDD), as well as psychiatrically healthy individuals was used. Differences in methylation across all CpGs within a CpG island and between the three diagnostic groups were assessed by 2-way mixed model analyses of variance.
  
  
  
  We found no significant results for SYN1 or SYN3, but there was a significant group difference in SYN2 methylation, as well as an overall pattern of hypomethylation across the CpG island. Furthermore, we found a significant inverse correlation of DNA methylation with SYN2a mRNA expression.
  
  
  
  These findings contribute to previous work showing dysregulation of Synapsins, particularly SYN2, in mood disorders and improve our understanding of the regulatory mechanisms that precipitate these changes likely leading to the BD or MDD phenotype.
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada.|Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors: Cristiana
authors: C
authors: Cruceanu
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada.|Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors: Elena
authors: E
authors: Kutsarova
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada.
authors: Elizabeth S
authors: ES
authors: Chen
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada.
authors: David R
authors: DR
authors: Checknita
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada.
authors: Corina
authors: C
authors: Nagy
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada.
authors: Juan Pablo
authors: JP
authors: Lopez
authors: Department of Psychiatry, Dalhousie University, Halifax, NS, Canada.
authors: Martin
authors: M
authors: Alda
authors: Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
authors: Guy A
authors: GA
authors: Rouleau
authors: McGill Group for Suicide Studies & Douglas Research Institute, McGill University, Montreal, QC, Canada. Gustavo.turecki@mcgill.ca.|Douglas Mental Health Institute, McGill University, 6875 LaSalle Blvd, Montreal, QC, H4H 1R3, Canada. Gustavo.turecki@mcgill.ca.
authors: Gustavo
authors: G
authors: Turecki
mesh_terms: D000328:Adult; D029681:Arabidopsis Proteins / Q000235:genetics*; D001714:Bipolar Disorder / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D018899:CpG Islands; D019175:DNA Methylation / Q000235:genetics*; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic / Q000235:genetics
chemical_list: D029681:Arabidopsis Proteins; D018797:Cell Cycle Proteins; C118817:SYN1 protein, Arabidopsis; C432544:SYN2 protein, Arabidopsis; C432545:SYN3 protein, Arabidopsis
keywords: Bipolar disorder; DNA Methylation; Epigenetics; Major depressive disorder; Mood disorders